WorldWideScience

Sample records for clathrin independent macropinocytosis-like

  1. Clathrin-independent endocytosis: mechanisms and function

    DEFF Research Database (Denmark)

    Sandvig, Kirsten; Pust, Sascha; Skotland, Tore

    2011-01-01

    It is now about 20 years since we first wrote reviews about clathrin-independent endocytosis. The challenge at the time was to convince the reader about its existence. Then the suggestion came up that caveolae might be responsible for the uptake. However, clearly this could not be the case since ...... having several functions of their own. This article aims at providing a brief update on the importance of clathrin-independent endocytic mechanisms, how the processes are regulated differentially, for instance on the poles of polarized cells, and the challenges in studying them....

  2. Duffy antigen receptor for chemokines mediates chemokine endocytosis through a macropinocytosis-like process in endothelial cells.

    Directory of Open Access Journals (Sweden)

    Yani Zhao

    Full Text Available The Duffy antigen receptor for chemokines (DARC shows high affinity binding to multiple inflammatory CC and CXC chemokines and is expressed by erythrocytes and endothelial cells. Recent evidence suggests that endothelial DARC facilitates chemokine transcytosis to promote neutrophil recruitment. However, the mechanism of chemokine endocytosis by DARC remains unclear.We investigated the role of several endocytic pathways in DARC-mediated ligand internalization. Here we report that, although DARC co-localizes with caveolin-1 in endothelial cells, caveolin-1 is dispensable for DARC-mediated (125I-CXCL1 endocytosis as knockdown of caveolin-1 failed to inhibit ligand internalization. (125I-CXCL1 endocytosis by DARC was also independent of clathrin and flotillin-1 but required cholesterol and was, in part, inhibited by silencing Dynamin II expression.(125I-CXCL1 endocytosis was inhibited by amiloride, cytochalasin D, and the PKC inhibitor Gö6976 whereas Platelet Derived Growth Factor (PDGF enhanced ligand internalization through DARC. The majority of DARC-ligand interactions occurred on the endothelial surface, with DARC identified along plasma membrane extensions with the appearance of ruffles, supporting the concept that DARC provides a high affinity scaffolding function for surface retention of chemokines on endothelial cells.These results show DARC-mediated chemokine endocytosis occurs through a macropinocytosis-like process in endothelial cells and caveolin-1 is dispensable for CXCL1 internalization.

  3. APC Inhibits Ligand-Independent Wnt Signaling by the Clathrin Endocytic Pathway.

    Science.gov (United States)

    Saito-Diaz, Kenyi; Benchabane, Hassina; Tiwari, Ajit; Tian, Ai; Li, Bin; Thompson, Joshua J; Hyde, Annastasia S; Sawyer, Leah M; Jodoin, Jeanne N; Santos, Eduardo; Lee, Laura A; Coffey, Robert J; Beauchamp, R Daniel; Williams, Christopher S; Kenworthy, Anne K; Robbins, David J; Ahmed, Yashi; Lee, Ethan

    2018-03-12

    Adenomatous polyposis coli (APC) mutations cause Wnt pathway activation in human cancers. Current models for APC action emphasize its role in promoting β-catenin degradation downstream of Wnt receptors. Unexpectedly, we find that blocking Wnt receptor activity in APC-deficient cells inhibits Wnt signaling independently of Wnt ligand. We also show that inducible loss of APC is rapidly followed by Wnt receptor activation and increased β-catenin levels. In contrast, APC2 loss does not promote receptor activation. We show that APC exists in a complex with clathrin and that Wnt pathway activation in APC-deficient cells requires clathrin-mediated endocytosis. Finally, we demonstrate conservation of this mechanism in Drosophila intestinal stem cells. We propose a model in which APC and APC2 function to promote β-catenin degradation, and APC also acts as a molecular "gatekeeper" to block receptor activation via the clathrin pathway. Copyright © 2018 Elsevier Inc. All rights reserved.

  4. Stochastic Modeling of the Clathrin-dependent and -independent Endocytic Pathways

    Science.gov (United States)

    Deng, Hua; Dutta, Prashanta; Liu, Jin

    2017-11-01

    Endocytosis is one of the important processes that bioparticles use to enter the cells. During endocytosis the membrane-bound vesicles are formed by the invagination of plasma membrane as a result of interactions among many proteins and cytoskeletons. The clathrin-mediated endocytosis is one of the most significant form of endocytosis, where the dynamic assembly of clathrin-coated pits play a critical role. While herpes simplex virus-1 has recently shown to infect cell by a novel phagocytosis-like endocytic pathway where actin polymerization may facilitate the viral entry. In this work, we propose a stochastic model for both clathrin-dependent and -independent endocytic pathways based on Monte Carlo simulations. The important roles of clathrin coating and actin cytoskeleton as well as the impact of other biological parameters are studied. Our preliminary results indicate that there exist an intermediate particle size and ligand density that maximize the internalization efficiency. Below a critical size or surface ligand density, it is difficult for the entry of a single particle, which means clustering may needed for more efficient internalization. We also find that lower membrane bending rigidity may help promote the bioparticle entry. Research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award Number R01GM122081.

  5. Endocytosis of HERG is clathrin-independent and involves arf6.

    Directory of Open Access Journals (Sweden)

    Rucha Karnik

    Full Text Available The hERG potassium channel is critical for repolarisation of the cardiac action potential. Reduced expression of hERG at the plasma membrane, whether caused by hereditary mutations or drugs, results in long QT syndrome and increases the risk of ventricular arrhythmias. Thus, it is of fundamental importance to understand how the density of this channel at the plasma membrane is regulated. We used antibodies to an extracellular native or engineered epitope, in conjunction with immunofluorescence and ELISA, to investigate the mechanism of hERG endocytosis in recombinant cells and validated the findings in rat neonatal cardiac myocytes. The data reveal that this channel undergoes rapid internalisation, which is inhibited by neither dynasore, an inhibitor of dynamin, nor a dominant negative construct of Rab5a, into endosomes that are largely devoid of the transferrin receptor. These results support a clathrin-independent mechanism of endocytosis and exclude involvement of dynamin-dependent caveolin and RhoA mechanisms. In agreement, internalised hERG displayed marked overlap with glycosylphosphatidylinositol-anchored GFP, a clathrin-independent cargo. Endocytosis was significantly affected by cholesterol extraction with methyl-β-cyclodextrin and inhibition of Arf6 function with dominant negative Arf6-T27N-eGFP. Taken together, we conclude that hERG undergoes clathrin-independent endocytosis via a mechanism involving Arf6.

  6. Endocytosis of hERG Is Clathrin-Independent and Involves Arf6

    Science.gov (United States)

    Abuarab, Nada; Smith, Andrew J.; Hardy, Matthew E. L.; Elliott, David J. S.; Sivaprasadarao, Asipu

    2013-01-01

    The hERG potassium channel is critical for repolarisation of the cardiac action potential. Reduced expression of hERG at the plasma membrane, whether caused by hereditary mutations or drugs, results in long QT syndrome and increases the risk of ventricular arrhythmias. Thus, it is of fundamental importance to understand how the density of this channel at the plasma membrane is regulated. We used antibodies to an extracellular native or engineered epitope, in conjunction with immunofluorescence and ELISA, to investigate the mechanism of hERG endocytosis in recombinant cells and validated the findings in rat neonatal cardiac myocytes. The data reveal that this channel undergoes rapid internalisation, which is inhibited by neither dynasore, an inhibitor of dynamin, nor a dominant negative construct of Rab5a, into endosomes that are largely devoid of the transferrin receptor. These results support a clathrin-independent mechanism of endocytosis and exclude involvement of dynamin-dependent caveolin and RhoA mechanisms. In agreement, internalised hERG displayed marked overlap with glycosylphosphatidylinositol-anchored GFP, a clathrin-independent cargo. Endocytosis was significantly affected by cholesterol extraction with methyl-β-cyclodextrin and inhibition of Arf6 function with dominant negative Arf6-T27N-eGFP. Taken together, we conclude that hERG undergoes clathrin-independent endocytosis via a mechanism involving Arf6. PMID:24392021

  7. Unraveling a molecular determinant for clathrin-independent internalization of the M2 muscarinic acetylcholine receptor

    Science.gov (United States)

    Wan, Min; Zhang, Wenhua; Tian, Yangli; Xu, Chanjuan; Xu, Tao; Liu, Jianfeng; Zhang, Rongying

    2015-01-01

    Endocytosis and postendocytic sorting of G-protein-coupled receptors (GPCRs) is important for the regulation of both their cell surface density and signaling profile. Unlike the mechanisms of clathrin-dependent endocytosis (CDE), the mechanisms underlying the control of GPCR signaling by clathrin-independent endocytosis (CIE) remain largely unknown. Among the muscarinic acetylcholine receptors (mAChRs), the M4 mAChR undergoes CDE and recycling, whereas the M2 mAChR is internalized through CIE and targeted to lysosomes. Here we investigated the endocytosis and postendocytic trafficking of M2 mAChR based on a comparative analysis of the third cytoplasmic domain in M2 and M4 mAChRs. For the first time, we identified that the sequence 374KKKPPPS380 servers as a sorting signal for the clathrin-independent internalization of M2 mAChR. Switching 374KKKPPPS380 to the i3 loop of the M4 mAChR shifted the receptor into lysosomes through the CIE pathway; and therefore away from CDE and recycling. We also found another previously unidentified sequence that guides CDE of the M2 mAChR, 361VARKIVKMTKQPA373, which is normally masked in the presence of the downstream sequence 374KKKPPPS380. Taken together, our data indicate that endocytosis and postendocytic sorting of GPCRs that undergo CIE could be sequence-dependent. PMID:26094760

  8. Endocytic crosstalk: cavins, caveolins, and caveolae regulate clathrin-independent endocytosis.

    Directory of Open Access Journals (Sweden)

    Natasha Chaudhary

    2014-04-01

    Full Text Available Several studies have suggested crosstalk between different clathrin-independent endocytic pathways. However, the molecular mechanisms and functional relevance of these interactions are unclear. Caveolins and cavins are crucial components of caveolae, specialized microdomains that also constitute an endocytic route. Here we show that specific caveolar proteins are independently acting negative regulators of clathrin-independent endocytosis. Cavin-1 and Cavin-3, but not Cavin-2 or Cavin-4, are potent inhibitors of the clathrin-independent carriers/GPI-AP enriched early endosomal compartment (CLIC/GEEC endocytic pathway, in a process independent of caveola formation. Caveolin-1 (CAV1 and CAV3 also inhibit the CLIC/GEEC pathway upon over-expression. Expression of caveolar protein leads to reduction in formation of early CLIC/GEEC carriers, as detected by quantitative electron microscopy analysis. Furthermore, the CLIC/GEEC pathway is upregulated in cells lacking CAV1/Cavin-1 or with reduced expression of Cavin-1 and Cavin-3. Inhibition by caveolins can be mimicked by the isolated caveolin scaffolding domain and is associated with perturbed diffusion of lipid microdomain components, as revealed by fluorescence recovery after photobleaching (FRAP studies. In the absence of cavins (and caveolae CAV1 is itself endocytosed preferentially through the CLIC/GEEC pathway, but the pathway loses polarization and sorting attributes with consequences for membrane dynamics and endocytic polarization in migrating cells and adult muscle tissue. We also found that noncaveolar Cavin-1 can act as a modulator for the activity of the key regulator of the CLIC/GEEC pathway, Cdc42. This work provides new insights into the regulation of noncaveolar clathrin-independent endocytosis by specific caveolar proteins, illustrating multiple levels of crosstalk between these pathways. We show for the first time a role for specific cavins in regulating the CLIC/GEEC pathway, provide

  9. Chemerin C9 peptide induces receptor internalization through a clathrin-independent pathway

    Science.gov (United States)

    Zhou, Jun-xian; Liao, Dan; Zhang, Shuo; Cheng, Ni; He, Hui-qiong; Ye, Richard D

    2014-01-01

    Aim: The chemerin receptor CMKLR1 is one type of G protein-coupled receptors abundant in monocyte-derived dendritic cells and macrophages, which plays a key role in the entry of a subset of immunodeficiency viruses including HIV/SIV into lymphocytes and macrophages. The aim of this work was to investigate how CMKLR1 was internalized and whether its internalization affected cell signaling in vitro. Methods: Rat basophilic leukemia RBL-2H3 cells, HEK 293 cells, and HeLa cells were used. CMKLR1 internalization was visualized by confocal microscopy imaging or using a FACScan flow cytometer. Six potential phosphorylation sites (Ser337, Ser343, Thr352, Ser344, Ser347, and Ser350) in CMKLR1 were substituted with alanine using site-directed mutagenesis. Heterologous expression of wild type and mutant CMKLR1 allowed for functional characterization of endocytosis, Ca2+ flux and extracellular signal-regulated kinase (ERK) phosphorylation. Results: Chemerin and the chemerin-derived nonapeptide (C9) induced dose-dependent loss of cell surface CMKLR1-GFP fusion protein and increased its intracellular accumulation in HEK 293 cells and RBL-2H3 cells stably expressing CMKLR1. Up to 90% of CMKLR1 was internalized after treatment with C9 (1 μmol/L). By using different agents, it was demonstrated that clathrin-independent mechanism was involved in CMKLR1 internalization. Mutations in Ser343 for G protein-coupled receptor kinase phosphorylation and in Ser347 for PKC phosphorylation abrogated CMKLR1 internalization. Loss of CMKLR1 internalization partially enhanced the receptor signaling, as shown by increased Ca2+ flux and a shorter latency to peak level of ERK phosphorylation. Conclusion: CMKLR1 internalization occurs in a clathrin-independent manner, which negatively regulated the receptor-mediated Ca2+ flux and ERK phosphorylation. PMID:24658352

  10. Clathrin-independent endocytosis: from nonexisting to an extreme degree of complexity

    DEFF Research Database (Denmark)

    Sandvig, Kirsten; Torgersen, Maria Lyngaas; Raa, Hilde Andersen

    2008-01-01

    Today it is generally accepted that there are several endocytic mechanisms, both the clathrin-dependent one and mechanisms which operate without clathrin and with different requirements when it comes to dynamin, small GTP-binding proteins of the Rho family and specific lipids. It should be noted ...... to give an overview of the complexity of the mechanisms and their regulation....

  11. Clathrin- and Caveolin-Independent Entry of Human Papillomavirus Type 16—Involvement of Tetraspanin-Enriched Microdomains (TEMs)

    Science.gov (United States)

    Spoden, Gilles; Freitag, Kirsten; Husmann, Matthias; Boller, Klaus; Sapp, Martin; Lambert, Carsten; Florin, Luise

    2008-01-01

    Background Infectious entry of human papillomaviruses into their host cells is an important step in the viral life cycle. For cell binding these viruses use proteoglycans as initial attachment sites. Subsequent transfer to a secondary receptor molecule seems to be involved in virus uptake. Depending on the papillomavirus subtype, it has been reported that entry occurs by clathrin- or caveolin-mediated mechanisms. Regarding human papillomavirus type 16 (HPV16), the primary etiologic agent for development of cervical cancer, clathrin-mediated endocytosis was described as infectious entry pathway. Methodology/Principal Findings Using immunofluorescence and infection studies we show in contrast to published data that infectious entry of HPV16 occurs in a clathrin- and caveolin-independent manner. Inhibition of clathrin- and caveolin/raft-dependent endocytic pathways by dominant-negative mutants and siRNA-mediated knockdown, as well as inhibition of dynamin function, did not impair infection. Rather, we provide evidence for involvement of tetraspanin-enriched microdomains (TEMs) in HPV16 endocytosis. Following cell attachment, HPV16 particles colocalized with the tetraspanins CD63 and CD151 on the cell surface. Notably, tetraspanin-specific antibodies and siRNA inhibited HPV16 cell entry and infection, confirming the importance of TEMs for infectious endocytosis of HPV16. Conclusions/Significance Tetraspanins fulfill various roles in the life cycle of a number of important viral pathogens, including human immunodeficiency virus (HIV) and hepatitis C virus (HCV). However, their involvement in endocytosis of viral particles has not been proven. Our data indicate TEMs as a novel clathrin- and caveolin-independent invasion route for viral pathogens and especially HPV16. PMID:18836553

  12. Clathrin- and caveolin-independent entry of human papillomavirus type 16--involvement of tetraspanin-enriched microdomains (TEMs.

    Directory of Open Access Journals (Sweden)

    Gilles Spoden

    Full Text Available BACKGROUND: Infectious entry of human papillomaviruses into their host cells is an important step in the viral life cycle. For cell binding these viruses use proteoglycans as initial attachment sites. Subsequent transfer to a secondary receptor molecule seems to be involved in virus uptake. Depending on the papillomavirus subtype, it has been reported that entry occurs by clathrin- or caveolin-mediated mechanisms. Regarding human papillomavirus type 16 (HPV16, the primary etiologic agent for development of cervical cancer, clathrin-mediated endocytosis was described as infectious entry pathway. METHODOLOGY/PRINCIPAL FINDINGS: Using immunofluorescence and infection studies we show in contrast to published data that infectious entry of HPV16 occurs in a clathrin- and caveolin-independent manner. Inhibition of clathrin- and caveolin/raft-dependent endocytic pathways by dominant-negative mutants and siRNA-mediated knockdown, as well as inhibition of dynamin function, did not impair infection. Rather, we provide evidence for involvement of tetraspanin-enriched microdomains (TEMs in HPV16 endocytosis. Following cell attachment, HPV16 particles colocalized with the tetraspanins CD63 and CD151 on the cell surface. Notably, tetraspanin-specific antibodies and siRNA inhibited HPV16 cell entry and infection, confirming the importance of TEMs for infectious endocytosis of HPV16. CONCLUSIONS/SIGNIFICANCE: Tetraspanins fulfill various roles in the life cycle of a number of important viral pathogens, including human immunodeficiency virus (HIV and hepatitis C virus (HCV. However, their involvement in endocytosis of viral particles has not been proven. Our data indicate TEMs as a novel clathrin- and caveolin-independent invasion route for viral pathogens and especially HPV16.

  13. Clathrin- and caveolin-independent entry of human papillomavirus type 16--involvement of tetraspanin-enriched microdomains (TEMs).

    Science.gov (United States)

    Spoden, Gilles; Freitag, Kirsten; Husmann, Matthias; Boller, Klaus; Sapp, Martin; Lambert, Carsten; Florin, Luise

    2008-10-02

    Infectious entry of human papillomaviruses into their host cells is an important step in the viral life cycle. For cell binding these viruses use proteoglycans as initial attachment sites. Subsequent transfer to a secondary receptor molecule seems to be involved in virus uptake. Depending on the papillomavirus subtype, it has been reported that entry occurs by clathrin- or caveolin-mediated mechanisms. Regarding human papillomavirus type 16 (HPV16), the primary etiologic agent for development of cervical cancer, clathrin-mediated endocytosis was described as infectious entry pathway. Using immunofluorescence and infection studies we show in contrast to published data that infectious entry of HPV16 occurs in a clathrin- and caveolin-independent manner. Inhibition of clathrin- and caveolin/raft-dependent endocytic pathways by dominant-negative mutants and siRNA-mediated knockdown, as well as inhibition of dynamin function, did not impair infection. Rather, we provide evidence for involvement of tetraspanin-enriched microdomains (TEMs) in HPV16 endocytosis. Following cell attachment, HPV16 particles colocalized with the tetraspanins CD63 and CD151 on the cell surface. Notably, tetraspanin-specific antibodies and siRNA inhibited HPV16 cell entry and infection, confirming the importance of TEMs for infectious endocytosis of HPV16. Tetraspanins fulfill various roles in the life cycle of a number of important viral pathogens, including human immunodeficiency virus (HIV) and hepatitis C virus (HCV). However, their involvement in endocytosis of viral particles has not been proven. Our data indicate TEMs as a novel clathrin- and caveolin-independent invasion route for viral pathogens and especially HPV16.

  14. Clathrin-independent pathways do not contribute significantly to endocytic flux.

    Science.gov (United States)

    Bitsikas, Vassilis; Corrêa, Ivan R; Nichols, Benjamin J

    2014-09-17

    Several different endocytic pathways have been proposed to function in mammalian cells. Clathrin-coated pits are well defined, but the identity, mechanism and function of alternative pathways have been controversial. Here we apply universal chemical labelling of plasma membrane proteins to define all primary endocytic vesicles, and labelling of specific proteins with a reducible SNAP-tag substrate. These approaches provide high temporal resolution and stringent discrimination between surface-connected and intracellular membranes. We find that at least 95% of the earliest detectable endocytic vesicles arise from clathrin-coated pits. GPI-anchored proteins, candidate cargoes for alternate pathways, are also found to enter the cell predominantly via coated pits. Experiments employing a mutated clathrin adaptor reveal distinct mechanisms for sorting into coated pits, and thereby explain differential effects on the uptake of transferrin and GPI-anchored proteins. These data call for a revision of models for the activity and diversity of endocytic pathways in mammalian cells.

  15. Endocytosis-independent function of clathrin heavy chain in the control of basal NF-κB activation.

    Directory of Open Access Journals (Sweden)

    Man Lyang Kim

    Full Text Available BACKGROUND: Nuclear factor-κB (NF-κB is a transcription factor that regulates the transcription of genes involved in a variety of biological processes, including innate and adaptive immunity, stress responses and cell proliferation. Constitutive or excessive NF-κB activity has been associated with inflammatory disorders and higher risk of cancer. In contrast to the mechanisms controlling inducible activation, the regulation of basal NF-κB activation is not well understood. Here we test whether clathrin heavy chain (CHC contributes to the regulation of basal NF-κB activity in epithelial cells. METHODOLOGY: Using RNA interference to reduce endogenous CHC expression, we found that CHC is required to prevent constitutive activation of NF-κB and gene expression. Immunofluorescence staining showed constitutive nuclear localization of the NF-κB subunit p65 in absence of stimulation after CHC knockdown. Elevated basal p65 nuclear localization is caused by constitutive phosphorylation and degradation of inhibitor of NF-κB alpha (IκBα through an IκB kinase α (IKKα-dependent mechanism. The role of CHC in NF-κB signaling is functionally relevant as constitutive expression of the proinflammatory chemokine interleukin-8 (IL-8, whose expression is regulated by NF-κB, was found after CHC knockdown. Disruption of clathrin-mediated endocytosis by chemical inhibition or depletion of the μ2-subunit of the endocytosis adaptor protein AP-2, and knockdown of clathrin light chain a (CHLa, failed to induce constitutive NF-κB activation and IL-8 expression, showing that CHC acts on NF-κB independently of endocytosis and CLCa. CONCLUSIONS: We conclude that CHC functions as a built-in molecular brake that ensures a tight control of basal NF-κB activation and gene expression in unstimulated cells. Furthermore, our data suggest a potential link between a defect in CHC expression and chronic inflammation disorder and cancer.

  16. Deletion of the distal COOH-terminus of the A2B adenosine receptor switches internalization to an arrestin- and clathrin-independent pathway and inhibits recycling.

    Science.gov (United States)

    Mundell, S J; Matharu, A-L; Nisar, S; Palmer, T M; Benovic, J L; Kelly, E

    2010-02-01

    We have investigated the effect of deletions of a postsynaptic density, disc large and zo-1 protein (PDZ) motif at the end of the COOH-terminus of the rat A(2B) adenosine receptor on intracellular trafficking following long-term exposure to the agonist 5'-(N-ethylcarboxamido)-adenosine. The trafficking of the wild type A(2B) adenosine receptor and deletion mutants expressed in Chinese hamster ovary cells was studied using an enzyme-linked immunosorbent assay in combination with immunofluorescence microscopy. The wild type A(2B) adenosine receptor and deletion mutants were all extensively internalized following prolonged treatment with NECA. The intracellular compartment through which the Gln(325)-stop receptor mutant, which lacks the Type II PDZ motif found in the wild type receptor initially trafficked was not the same as the wild type receptor. Expression of dominant negative mutants of arrestin-2, dynamin or Eps-15 inhibited internalization of wild type and Leu(330)-stop receptors, whereas only dominant negative mutant dynamin inhibited agonist-induced internalization of Gln(325)-stop, Ser(326)-stop and Phe(328)-stop receptors. Following internalization, the wild type A(2B) adenosine receptor recycled rapidly to the cell surface, whereas the Gln(325)-stop receptor did not recycle. Deletion of the COOH-terminus of the A(2B) adenosine receptor beyond Leu(330) switches internalization from an arrestin- and clathrin-dependent pathway to one that is dynamin dependent but arrestin and clathrin independent. The presence of a Type II PDZ motif appears to be essential for arrestin- and clathrin-dependent internalization, as well as recycling of the A(2B) adenosine receptor following prolonged agonist addition.

  17. Cellular entry of ebola virus involves uptake by a macropinocytosis-like mechanism and subsequent trafficking through early and late endosomes.

    Directory of Open Access Journals (Sweden)

    Mohammad F Saeed

    2010-09-01

    Full Text Available Zaire ebolavirus (ZEBOV, a highly pathogenic zoonotic virus, poses serious public health, ecological and potential bioterrorism threats. Currently no specific therapy or vaccine is available. Virus entry is an attractive target for therapeutic intervention. However, current knowledge of the ZEBOV entry mechanism is limited. While it is known that ZEBOV enters cells through endocytosis, which of the cellular endocytic mechanisms used remains unclear. Previous studies have produced differing outcomes, indicating potential involvement of multiple routes but many of these studies were performed using noninfectious surrogate systems such as pseudotyped retroviral particles, which may not accurately recapitulate the entry characteristics of the morphologically distinct wild type virus. Here we used replication-competent infectious ZEBOV as well as morphologically similar virus-like particles in specific infection and entry assays to demonstrate that in HEK293T and Vero cells internalization of ZEBOV is independent of clathrin, caveolae, and dynamin. Instead the uptake mechanism has features of macropinocytosis. The binding of virus to cells appears to directly stimulate fluid phase uptake as well as localized actin polymerization. Inhibition of key regulators of macropinocytosis including Pak1 and CtBP/BARS as well as treatment with the drug EIPA, which affects macropinosome formation, resulted in significant reduction in ZEBOV entry and infection. It is also shown that following internalization, the virus enters the endolysosomal pathway and is trafficked through early and late endosomes, but the exact site of membrane fusion and nucleocapsid penetration in the cytoplasm remains unclear. This study identifies the route for ZEBOV entry and identifies the key cellular factors required for the uptake of this filamentous virus. The findings greatly expand our understanding of the ZEBOV entry mechanism that can be applied to development of new

  18. Differential requirements of arrestin-3 and clathrin for ligand-dependent and -independent internalization of human G protein-coupled receptor 40.

    Science.gov (United States)

    Qian, Jing; Wu, Chun; Chen, Xiaopan; Li, Xiangmei; Ying, Guoyuan; Jin, Lili; Ma, Qiang; Li, Guo; Shi, Ying; Zhang, Guozheng; Zhou, Naiming

    2014-11-01

    G protein-coupled receptor 40 (GPR40) is believed to be an attractive target to enhance insulin secretion in patients with type 2 diabetes. GPR40 has been found to couple to Gq protein, leading to the activation of phospholipase C and subsequent increases in the intracellular Ca(2+) level. However, the underlying mechanisms that regulate the internalization and desensitization of GPR40 remain to be elucidated. In the present study, a construct of GPR40 fused with enhanced green fluorescent protein (EGFP) at its C-terminus was constructed for direct imaging of the localization and internalization of GPR40 by confocal microscopy. In stably transfected HEK-293 cells, GPR40 receptors underwent rapid agonist-induced internalization and constitutive ligand-independent internalization. Our data demonstrated that the agonist-mediated internalization of GPR40 was significantly blocked by hypertonic sucrose treatment and by siRNA mediated depletion of the heavy chain of clathrin. In contrast, constitutive GPR40 internalization was not affected by hypertonic sucrose or by knock-down of clathrin expression, but it was affected by treatment with methyl-β-cyclodextrin (MβCD) and nystatin. Furthermore, our results using an arrestin-3-EGFP redistribution assay and siRNA-mediated knock-down of arrestin-3 and GRK2 expression revealed that arrestin-3 and GRK2 play an essential role in the regulation of agonist-mediated GPR40 internalization, but are not involved in the regulation of constitutive GPR40 internalization. Additionally, our observation showed that upon activation by agonist, the internalized GPR40 receptors were rapidly recycled back to the plasma membrane via Rab4/Rab5 positive endosomes, whereas the constitutively internalized GPR40 receptors were recycled back to the cell surface through Rab5 positive endosomes. Because FFA receptors exhibit a high level of homology, our observations could be applicable to other members of this family. Copyright © 2014 Elsevier Inc

  19. Distinct cargo-specific response landscapes underpin the complex and nuanced role of galectin-glycan interactions in clathrin-independent endocytosis.

    Science.gov (United States)

    Mathew, Mohit P; Donaldson, Julie G

    2018-05-11

    Clathrin-independent endocytosis (CIE) is a form of endocytosis that lacks a defined cytoplasmic machinery. Here, we asked whether glycan interactions, acting from the outside, could be a part of that endocytic machinery. We show that the perturbation of global cellular patterns of protein glycosylation by modulation of metabolic flux affects CIE. Interestingly, these changes in glycosylation had cargo-specific effects. For example, in HeLa cells, GlcNAc treatment, which increases glycan branching, increased major histocompatibility complex class I (MHCI) internalization but inhibited CIE of the glycoprotein CD59 molecule (CD59). The effects of knocking down the expression of galectin 3, a carbohydrate-binding protein and an important player in galectin-glycan interactions, were also cargo-specific and stimulated CD59 uptake. By contrast, inhibition of all galectin-glycan interactions by lactose inhibited CIE of both MHCI and CD59. None of these treatments affected clathrin-mediated endocytosis, implying that glycosylation changes specifically affect CIE. We also found that the galectin lattice tailors membrane fluidity and cell spreading. Furthermore, changes in membrane dynamics mediated by the galectin lattice affected macropinocytosis, an altered form of CIE, in HT1080 cells. Our results suggest that glycans play an important and nuanced role in CIE, with each cargo being affected uniquely by alterations in galectin and glycan profiles and their interactions. We conclude that galectin-driven effects exist on a continuum from stimulatory to inhibitory, with distinct CIE cargo proteins having unique response landscapes and with different cell types starting at different positions on these conceptual landscapes.

  20. The LXR-IDOL axis defines a clathrin-, caveolae-, and dynamin-independent endocytic route for LDLR internalization and lysosomal degradation

    NARCIS (Netherlands)

    Sorrentino, Vincenzo; Nelson, Jessica K.; Maspero, Elena; Marques, André R. A.; Scheer, Lilith; Polo, Simona; Zelcer, Noam

    2013-01-01

    Low density lipoprotein (LDL) cholesterol is taken up into cells via clathrin-mediated endocytosis of the LDL receptor (LDLR). Following dissociation of the LDLR-LDL complex, LDL is directed to lysosomes whereas the LDLR recycles to the plasma membrane. Activation of the sterol-sensing nuclear

  1. Shiga Toxin Increases Formation of Clathrin-Coated Pits through Syk Kinase

    DEFF Research Database (Denmark)

    Utskarpen, Audrun; Massol, Ramiro; van Deurs, Bo

    2010-01-01

    Clathrin-dependent endocytosis is a main entry mechanism for the glycolipid-binding Shiga toxin (Stx), although clathrin-independent pathways are also involved. Binding of Stx to its receptor Gb3 not only is essential for Stx retrograde transport to the endoplasmic reticulum and toxicity but also...... activates signaling through the tyrosine kinase Syk. We previously described that Syk activity is important for Stx entry, but it remained unclear how this kinase modulates endocytosis of Stx. Here we characterized the effects of Stx and Syk on clathrin-coated pit formation. We found that acute treatment...

  2. KEY INTERACTIONS FOR CLATHRIN COAT STABILITY

    Science.gov (United States)

    Böcking, Till; Aguet, Francois; Rapoport, Iris; Banzhaf, Manuel; Yu, Anan; Zeeh, Jean Christophe; Kirchhausen, Tom

    2014-01-01

    SUMMARY Clathrin-coated vesicles are major carriers of vesicular traffic in eukaryotic cells. This endocytic pathway relies on cycles of clathrin coat assembly and Hsc70-mediated disassembly. Here we identify histidine residues as major determinants of lattice assembly and stability. They are located at the invariant interface between the proximal and distal segments of clathrin heavy chains, in triskelions centered on two adjacent vertices of the coated-vesicle lattice. Mutation of these histidine to glutamine alters the pH dependence of coat stability. We then describe single-particle fluorescence imaging experiments in which we follow the effect of these histidine mutations on susceptibility to Hsc70-dependent uncoating. Coats destabilized by these mutations require fewer Hsc70 molecules to initiate disassembly as predicted by a model in which Hsc70 traps conformational distortions during the auxilin- and Hsc70:ATP-mediated uncoating reaction. PMID:24815030

  3. Lysosomal enzyme delivery by ICAM-1-targeted nanocarriers bypassing glycosylation- and clathrin-dependent endocytosis.

    Science.gov (United States)

    Muro, Silvia; Schuchman, Edward H; Muzykantov, Vladimir R

    2006-01-01

    Enzyme replacement therapy, a state-of-the-art treatment for many lysosomal storage disorders, relies on carbohydrate-mediated binding of recombinant enzymes to receptors that mediate lysosomal delivery via clathrin-dependent endocytosis. Suboptimal glycosylation of recombinant enzymes and deficiency of clathrin-mediated endocytosis in some lysosomal enzyme-deficient cells limit delivery and efficacy of enzyme replacement therapy for lysosomal disorders. We explored a novel delivery strategy utilizing nanocarriers targeted to a glycosylation- and clathrin-independent receptor, intercellular adhesion molecule (ICAM)-1, a glycoprotein expressed on diverse cell types, up-regulated and functionally involved in inflammation, a hallmark of many lysosomal disorders. We targeted recombinant human acid sphingomyelinase (ASM), deficient in types A and B Niemann-Pick disease, to ICAM-1 by loading this enzyme to nanocarriers coated with anti-ICAM. Anti-ICAM/ASM nanocarriers, but not control ASM or ASM nanocarriers, bound to ICAM-1-positive cells (activated endothelial cells and Niemann-Pick disease patient fibroblasts) via ICAM-1, in a glycosylation-independent manner. Anti-ICAM/ASM nanocarriers entered cells via CAM-mediated endocytosis, bypassing the clathrin-dependent pathway, and trafficked to lysosomes, where delivered ASM displayed stable activity and alleviated lysosomal lipid accumulation. Therefore, lysosomal enzyme targeting using nanocarriers targeted to ICAM-1 bypasses defunct pathways and may improve the efficacy of enzyme replacement therapy for lysosomal disorders, such as Niemann-Pick disease.

  4. Clathrin is spindle-associated but not essential for mitosis.

    Directory of Open Access Journals (Sweden)

    Joana Borlido

    Full Text Available Clathrin is a multimeric protein involved in vesicle coat assembly. Recently clathrin distribution was reported to change during the cell cycle and was found to associate with the mitotic spindle. Here we test whether the recruitment of clathrin to the spindle is indicative of a critical functional contribution to mitosis.Previously a chicken pre-B lymphoma cell line (DKO-R was developed in which the endogenous clathrin heavy chain alleles were replaced with the human clathrin heavy chain under the control of a tetracycline-regulatable promoter. Receptor-mediated and fluid-phase endocytosis were significantly inhibited in this line following clathrin knockout, and we used this to explore the significance of clathrin heavy chain expression for cell cycle progression. We confirmed using confocal microscopy that clathrin colocalised with tubulin at mitotic spindles. Using a propidium iodide flow cytometric assay we found no statistical difference in the cell cycle distribution of the knockout cells versus the wild-type. Additionally, we showed that the ploidy and the recovery kinetics following cell cycle arrest with nocodazole were unchanged by repressing clathrin heavy chain expression.We conclude that the association of clathrin with the mitotic spindle and the contribution of clathrin to endocytosis are evolutionarily conserved. However we find that the contribution of clathrin to mitosis is less robust and dependent on cellular context. In other cell-lines silencing RNA has been used by others to knockdown clathrin expression resulting in an increase in the mitotic index of the cells. We show an effect on the G2/M phase population of clathrin knockdown in HEK293 cells but show that repressing clathrin expression in the DKO-R cell-line has no effect on the size of this population. Consequently this work highlights the need for a more detailed molecular understanding of the recruitment and function of clathrin at the spindle, since the

  5. Weak Molecular Interactions in Clathrin-Mediated Endocytosis

    Directory of Open Access Journals (Sweden)

    Sarah M. Smith

    2017-11-01

    Full Text Available Clathrin-mediated endocytosis is a process by which specific molecules are internalized from the cell periphery for delivery to early endosomes. The key stages in this step-wise process, from the starting point of cargo recognition, to the later stage of assembly of the clathrin coat, are dependent on weak interactions between a large network of proteins. This review discusses the structural and functional data that have improved our knowledge and understanding of the main weak molecular interactions implicated in clathrin-mediated endocytosis, with a particular focus on the two key proteins: AP2 and clathrin.

  6. A balance between membrane elasticity and polymerization energy sets the shape of spherical clathrin coats

    Science.gov (United States)

    Saleem, Mohammed; Morlot, Sandrine; Hohendahl, Annika; Manzi, John; Lenz, Martin; Roux, Aurélien

    2015-02-01

    In endocytosis, scaffolding is one of the mechanisms to create membrane curvature by moulding the membrane into the spherical shape of the clathrin cage. However, the impact of membrane elastic parameters on the assembly and shape of clathrin lattices has never been experimentally evaluated. Here, we show that membrane tension opposes clathrin polymerization. We reconstitute clathrin budding in vitro with giant unilamellar vesicles (GUVs), purified adaptors and clathrin. By changing the osmotic conditions, we find that clathrin coats cause extensive budding of GUVs under low membrane tension while polymerizing into shallow pits under moderate tension. High tension fully inhibits polymerization. Theoretically, we predict the tension values for which transitions between different clathrin coat shapes occur. We measure the changes in membrane tension during clathrin polymerization, and use our theoretical framework to estimate the polymerization energy from these data. Our results show that membrane tension controls clathrin-mediated budding by varying the membrane budding energy.

  7. New clathrin-based nanoplatforms for magnetic resonance imaging.

    Directory of Open Access Journals (Sweden)

    Gordana D Vitaliano

    Full Text Available Magnetic Resonance Imaging (MRI has high spatial resolution, but low sensitivity for visualization of molecular targets in the central nervous system (CNS. Our goal was to develop a new MRI method with the potential for non-invasive molecular brain imaging. We herein introduce new bio-nanotechnology approaches for designing CNS contrast media based on the ubiquitous clathrin cell protein.The first approach utilizes three-legged clathrin triskelia modified to carry 81 gadolinium chelates. The second approach uses clathrin cages self-assembled from triskelia and designed to carry 432 gadolinium chelates. Clathrin triskelia and cages were characterized by size, structure, protein concentration, and chelate and gadolinium contents. Relaxivity was evaluated at 0.47 T. A series of studies were conducted to ascertain whether fluorescent-tagged clathrin nanoplatforms could cross the blood brain barriers (BBB unaided following intranasal, intravenous, and intraperitoneal routes of administration. Clathrin nanoparticles can be constituted as triskelia (18.5 nm in size, and as cages assembled from them (55 nm. The mean chelate: clathrin heavy chain molar ratio was 27.04±4.8: 1 for triskelia, and 4.2±1.04: 1 for cages. Triskelia had ionic relaxivity of 16 mM(-1 s(-1, and molecular relaxivity of 1,166 mM(-1 s(-1, while cages had ionic relaxivity of 81 mM(-1 s(-1 and molecular relaxivity of 31,512 mM(-1 s(-1. Thus, cages exhibited 20 times higher ionic relaxivity and 8,000-fold greater molecular relaxivity than gadopentetate dimeglumine. Clathrin nanoplatforms modified with fluorescent tags were able to cross or bypass the BBB without enhancements following intravenous, intraperitoneal and intranasal administration in rats.Use of clathrin triskelia and cages as carriers of CNS contrast media represents a new approach. This new biocompatible protein-based nanotechnology demonstrated suitable physicochemical properties to warrant further in vivo imaging and

  8. Roles of AP-2 in clathrin-mediated endocytosis.

    Directory of Open Access Journals (Sweden)

    Emmanuel Boucrot

    2010-05-01

    Full Text Available The notion that AP-2 clathrin adaptor is an essential component of an endocytic clathrin coat appears to conflict with recent observations that substantial AP-2 depletion, using RNA interference with synthesis of AP-2 subunits, fails to block uptake of certain ligands known to internalize through a clathrin-based pathway.We report here the use of in vivo imaging data obtained by spinning-disk confocal microscopy to study the formation of clathrin-coated structures at the plasma membranes of BSC1 and HeLa cells depleted by RNAi of the clathrin adaptor, AP-2. Very few clathrin coats continue to assemble after AP-2 knockdown. Moreover, there is a total absence of clathrin-containing structures completely lacking AP-2 while all the remaining coats still contain a small amount of AP-2. These observations suggest that AP-2 is essential for endocytic coated-pit and coated-vesicle formation. We also find that AP-2 knockdown strongly inhibits light-density lipoprotein (LDL receptor-mediated endocytosis, as long as cells are maintained in complete serum and at 37 degrees C. If cells are first incubated with LDL at 4 degrees C, followed by warming, there is little or no decrease in LDL uptake with respect to control cells. LDL uptake at 37 degrees C is also not affected in AP-2 depleted cells first deprived of LDL by incubation with either serum-starved or LDL-starved cells for 24 hr. The LDL-deprived cells display a significant increase in endocytic structures enriched on deeply invaginated tubes that contain LDL and we suggest that under this condition of stress, LDL might enter through this alternative pathway.These results suggest that AP-2 is essential for endocytic clathrin coated-pit and coated-vesicle formation. They also indicate that under normal conditions, functional endocytic clathrin coated pits are required for LDL internalization. We also show that under certain conditions of stress, cells can upregulate alternative endocytic structures

  9. Flat clathrin lattices: stable features of the plasma membrane.

    Science.gov (United States)

    Grove, Joe; Metcalf, Daniel J; Knight, Alex E; Wavre-Shapton, Silène T; Sun, Tony; Protonotarios, Emmanouil D; Griffin, Lewis D; Lippincott-Schwartz, Jennifer; Marsh, Mark

    2014-11-05

    Clathrin-mediated endocytosis (CME) is a fundamental property of eukaryotic cells. Classical CME proceeds via the formation of clathrin-coated pits (CCPs) at the plasma membrane, which invaginate to form clathrin-coated vesicles, a process that is well understood. However, clathrin also assembles into flat clathrin lattices (FCLs); these structures remain poorly described, and their contribution to cell biology is unclear. We used quantitative imaging to provide the first comprehensive description of FCLs and explore their influence on plasma membrane organization. Ultrastructural analysis by electron and superresolution microscopy revealed two discrete populations of clathrin structures. CCPs were typified by their sphericity, small size, and homogeneity. FCLs were planar, large, and heterogeneous and present on both the dorsal and ventral surfaces of cells. Live microscopy demonstrated that CCPs are short lived and culminate in a peak of dynamin recruitment, consistent with classical CME. In contrast, FCLs were long lived, with sustained association with dynamin. We investigated the biological relevance of FCLs using the chemokine receptor CCR5 as a model system. Agonist activation leads to sustained recruitment of CCR5 to FCLs. Quantitative molecular imaging indicated that FCLs partitioned receptors at the cell surface. Our observations suggest that FCLs provide stable platforms for the recruitment of endocytic cargo. © 2014 Grove et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  10. The non-canonical roles of clathrin and actin in pathogen internalization, egress and spread.

    Science.gov (United States)

    Humphries, Ashley C; Way, Michael

    2013-08-01

    The role of clathrin in pathogen entry has received much attention and has highlighted the adaptability of clathrin during internalization. Recent studies have now uncovered additional roles for clathrin and have put the spotlight on its role in pathogen spread. Here, we discuss the manipulation of clathrin by pathogens, with specific attention to the processes that occur at the plasma membrane. In the majority of cases, both clathrin and the actin cytoskeleton are hijacked, so we also examine the interplay between these two systems and their role during pathogen internalization, egress and spread.

  11. Modeling the self-assembly of clathrin coats

    NARCIS (Netherlands)

    Giani, Matteo

    2017-01-01

    The assembly of clathrin coats in the presence of adaptor proteins was studied through computer simulations using coarse-grained models and through statistical mechanics. Adopting a reductionist approach based on recent experimental results, we aimed at reproducing and studying the minimal

  12. Enhanced clathrin-dependent endocytosis in the absence of calnexin.

    Directory of Open Access Journals (Sweden)

    Hao-Dong Li

    Full Text Available Calnexin, together with calreticulin, constitute the calnexin/calreticulin cycle. Calnexin is a type I endoplasmic reticulum integral membrane protein and molecular chaperone responsible for the folding and quality control of newly-synthesized (glycoproteins. The endoplasmic reticulum luminal domain of calnexin is responsible for lectin-like activity and interaction with nascent polypeptide chains. The role of the C-terminal, cytoplasmic portion of calnexin is not clear.Using yeast two hybrid screen and immunoprecipitation techniques, we showed that the Src homology 3-domain growth factor receptor-bound 2-like (Endophilin interacting protein 1 (SGIP1, a neuronal specific regulator of endocytosis, forms complexes with the C-terminal cytoplasmic domain of calnexin. The calnexin cytoplasmic C-tail interacts with SGIP1 C-terminal domains containing the adaptor complexes medium subunit (Adap-Comp-Sub region. Calnexin-deficient cells have enhanced clathrin-dependent endocytosis in neuronal cells and mouse neuronal system. This is reversed by expression of full length calnexin or calnexin C-tail.We show that the effects of SGIP1 and calnexin C-tail on clathrin-dependent endocytosis are due to modulation of the internalization of the receptor-ligand complexes. Enhanced clathrin-dependent endocytosis in the absence of calnexin may contribute to the neurological phenotype of calnexin-deficient mice.

  13. Hypothesis review: are clathrin-mediated endocytosis and clathrin-dependent membrane and protein trafficking core pathophysiological processes in schizophrenia and bipolar disorder?

    LENUS (Irish Health Repository)

    2012-02-01

    Clathrin-mediated endocytosis (CME) is the best-characterized mechanism governing cellular membrane and protein trafficking. In this hypothesis review, we integrate recent evidence implicating CME and related cellular trafficking mechanisms in the pathophysiology of psychotic disorders such as schizophrenia and bipolar disorder. The evidence includes proteomic and genomic findings implicating proteins and genes of the clathrin interactome. Additionally, several important candidate genes for schizophrenia, such as dysbindin, are involved in processes closely linked to CME and membrane trafficking. We discuss that key aspects of psychosis neuropathology such as synaptic dysfunction, white matter changes and aberrant neurodevelopment are all influenced by clathrin-dependent processes, and that other cellular trafficking mechanisms previously linked to psychoses interact with the clathrin interactome in important ways. Furthermore, many antipsychotic drugs have been shown to affect clathrin-interacting proteins. We propose that the targeted pharmacological manipulation of the clathrin interactome may offer fruitful opportunities for novel treatments of schizophrenia.Molecular Psychiatry advance online publication, 11 October 2011; doi:10.1038\\/mp.2011.123.

  14. Association of the Hermansky-Pudlak syndrome type-3 protein with clathrin

    Directory of Open Access Journals (Sweden)

    Gahl William A

    2005-09-01

    Full Text Available Abstract Background Hermansky-Pudlak syndrome (HPS is a disorder of lysosome-related organelle biogenesis characterized by oculocutaneous albinism and prolonged bleeding. These clinical findings reflect defects in the formation of melanosomes in melanocytes and dense bodies in platelets. HPS type-3 (HPS-3 results from mutations in the HPS3 gene, which encodes a 1004 amino acid protein of unknown function that contains a predicted clathrin-binding motif (LLDFE at residues 172–176. Results Clathrin was co-immunoprecipitated by HPS3 antibodies from normal but not HPS3 null melanocytes. Normal melanocytes expressing a GFP-HPS3 fusion protein demonstrated partial co-localization of GFP-HPS3 with clathrin following a 20°C temperature block. GFP-HPS3 in which the predicted clathrin-binding domain of HPS3 was mutated (GFP-HPS3-delCBD did not co-localize with clathrin under the same conditions. Immunoelectron microscopy of normal melanocytes expressing GFP-HPS3 showed co-localization of GFP-HPS3 with clathrin, predominantly on small vesicles in the perinuclear region. In contrast, GFP-HPS3-delCBD did not co-localize with clathrin and exhibited a largely cytoplasmic distribution. Conclusion HPS3 associates with clathrin, predominantly on small clathrin-containing vesicles in the perinuclear region. This association most likely occurs directly via a functional clathrin-binding domain in HPS3. These results suggest a role for HPS3 and its protein complex, BLOC-2, in vesicle formation and trafficking.

  15. Bovine parvovirus uses clathrin-mediated endocytosis for cell entry.

    Science.gov (United States)

    Dudleenamjil, Enkhmart; Lin, Chin-Yo; Dredge, Devin; Murray, Byron K; Robison, Richard A; Johnson, F Brent

    2010-12-01

    Entry events of bovine parvovirus (BPV) were studied. Transmission electron micrographs of infected cells showed virus particles in cytoplasmic vesicles. Chemical inhibitors that block certain aspects of the cellular machinery were employed to assess viral dependency upon those cellular processes. Chlorpromazine, ammonium chloride, chloroquine and bafilamicin A1 were used to inhibit acidification of endosomes and clathrin-associated endocytosis. Nystatin was used as an inhibitor of the caveolae pathway. Cytochalasin D and ML-7 were used to inhibit actin and myosin functions, respectively. Nocodazole and colchicine were employed to inhibit microtubule activity. Virus entry was assessed by measuring viral transcription using real-time PCR, synthesis of capsid protein and assembly of infectious progeny virus in the presence of inhibitor blockage. The results indicated that BPV entry into embryonic bovine trachael cells utilizes endocytosis in clathrin-coated vesicles, is dependent upon acidification, and appears to be associated with actin and microtubule dependency. Evidence for viral entry through caveolae was not obtained. These findings provide a fuller understanding of the early cell-entry events of the replication cycle for members of the genus Bocavirus.

  16. Unraveling protein-protein interactions in clathrin assemblies via atomic force spectroscopy.

    Science.gov (United States)

    Jin, Albert J; Lafer, Eileen M; Peng, Jennifer Q; Smith, Paul D; Nossal, Ralph

    2013-03-01

    Atomic force microscopy (AFM), single molecule force spectroscopy (SMFS), and single particle force spectroscopy (SPFS) are used to characterize intermolecular interactions and domain structures of clathrin triskelia and clathrin-coated vesicles (CCVs). The latter are involved in receptor-mediated endocytosis (RME) and other trafficking pathways. Here, we subject individual triskelia, bovine-brain CCVs, and reconstituted clathrin-AP180 coats to AFM-SMFS and AFM-SPFS pulling experiments and apply novel analytics to extract force-extension relations from very large data sets. The spectroscopic fingerprints of these samples differ markedly, providing important new information about the mechanism of CCV uncoating. For individual triskelia, SMFS reveals a series of events associated with heavy chain alpha-helix hairpin unfolding, as well as cooperative unraveling of several hairpin domains. SPFS of clathrin assemblies exposes weaker clathrin-clathrin interactions that are indicative of inter-leg association essential for RME and intracellular trafficking. Clathrin-AP180 coats are energetically easier to unravel than the coats of CCVs, with a non-trivial dependence on force-loading rate. Published by Elsevier Inc.

  17. Membrane tension regulates clathrin-coated pit dynamics

    Science.gov (United States)

    Liu, Allen

    2014-03-01

    Intracellular organization depends on close communication between the extracellular environment and a network of cytoskeleton filaments. The interactions between cytoskeletal filaments and the plasma membrane lead to changes in membrane tension that in turns help regulate biological processes. Endocytosis is thought to be stimulated by low membrane tension and the removal of membrane increases membrane tension. While it is appreciated that the opposing effects of exocytosis and endocytosis have on keeping plasma membrane tension to a set point, it is not clear how membrane tension affects the dynamics of clathrin-coated pits (CCPs), the individual functional units of clathrin-mediated endocytosis. Furthermore, although it was recently shown that actin dynamics counteracts membrane tension during CCP formation, it is not clear what roles plasma membrane tension plays during CCP initiation. Based on the notion that plasma membrane tension is increased when the membrane area increases during cell spreading, we designed micro-patterned surfaces of different sizes to control the cell spreading sizes. Total internal reflection fluorescence microscopy of living cells and high content image analysis were used to quantify the dynamics of CCPs. We found that there is an increased proportion of CCPs with short (<20s) lifetime for cells on larger patterns. Interestingly, cells on larger patterns have higher CCP initiation density, an effect unexpected based on the conventional view of decreasing endocytosis with increasing membrane tension. Furthermore, by analyzing the intensity profiles of CCPs that were longer-lived, we found CCP intensity decreases with increasing cell size, indicating that the CCPs are smaller with increasing membrane tension. Finally, disruption of actin dynamics significantly increased the number of short-lived CCPs, but also decreased CCP initiation rate. Together, our study reveals new mechanistic insights into how plasma membrane tension regulates

  18. Loss of endocytic clathrin-coated pits upon acute depletion of phosphatidylinositol 4,5-bisphosphate.

    Science.gov (United States)

    Zoncu, Roberto; Perera, Rushika M; Sebastian, Rafael; Nakatsu, Fubito; Chen, Hong; Balla, Tamas; Ayala, Guillermo; Toomre, Derek; De Camilli, Pietro V

    2007-03-06

    Phosphatidylinositol 4,5-bisphosphate [PI(4,5)P(2)], a phosphoinositide concentrated predominantly in the plasma membrane, binds endocytic clathrin adaptors, many of their accessory factors, and a variety of actin-regulatory proteins. Here we have used fluorescent fusion proteins and total internal reflection fluorescence microscopy to investigate the effect of acute PI(4,5)P(2) breakdown on the dynamics of endocytic clathrin-coated pit components and of the actin regulatory complex, Arp2/3. PI(4,5)P(2) breakdown was achieved by the inducible recruitment to the plasma membrane of an inositol 5-phosphatase module through the rapamycin/FRB/FKBP system or by treatment with ionomycin. PI(4,5)P(2) depletion resulted in a dramatic loss of clathrin puncta, which correlated with a massive dissociation of endocytic adaptors from the plasma membrane. Remaining clathrin spots at the cell surface had only weak fluorescence and were static over time. Dynamin and the p20 subunit of the Arp2/3 actin regulatory complex, which were concentrated at late-stage clathrin-coated pits and in lamellipodia, also dissociated from the plasma membrane, and these changes correlated with an arrest of motility at the cell edge. These findings demonstrate the critical importance of PI(4,5)P(2) in clathrin coat dynamics and Arp2/3-dependent actin regulation.

  19. Correlated Fluorescence-Atomic Force Microscopy Studies of the Clathrin Mediated Endocytosis in SKMEL Cells

    Science.gov (United States)

    Smith, Steve; Hor, Amy; Luu, Anh; Kang, Lin; Scott, Brandon; Bailey, Elizabeth; Hoppe, Adam

    Clathrin-mediated endocytosis is one of the central pathways for cargo transport into cells, and plays a major role in the maintenance of cellular functions, such as intercellular signaling, nutrient intake, and turnover of plasma membrane in cells. The clathrin-mediated endocytosis process involves invagination and formation of clathrin-coated vesicles. However, the biophysical mechanisms of vesicle formation are still debated. We investigate clathrin vesicle formation mechanisms through the utilization of tapping-mode atomic force microscopy for high resolution topographical imaging in neutral buffer solution of unroofed cells exposing the inner membrane, combined with fluorescence imaging to definitively label intracellular constituents with specific fluorescent fusion proteins (actin filaments labeled with green phalloidin-antibody and clathrin coated vesicles with the fusion protein Tq2) in SKMEL (Human Melanoma) cells. Results from our work are compared against dynamical polarized total internal fluorescence (TIRF), super-resolution photo-activated localization microscopy (PALM) and transmission electron microscopy (TEM) to draw conclusions regarding the prominent model of vesicle formation in clathrin-mediated endocytosis. Funding provided by NSF MPS/DMR/BMAT award # 1206908.

  20. Endocytosis of G protein-coupled receptors is regulated by clathrin light chain phosphorylation.

    Science.gov (United States)

    Ferreira, Filipe; Foley, Matthew; Cooke, Alex; Cunningham, Margaret; Smith, Gemma; Woolley, Robert; Henderson, Graeme; Kelly, Eamonn; Mundell, Stuart; Smythe, Elizabeth

    2012-08-07

    Signaling by transmembrane receptors such as G protein-coupled receptors (GPCRs) occurs at the cell surface and throughout the endocytic pathway, and signaling from the cell surface may differ in magnitude and downstream output from intracellular signaling. As a result, the rate at which signaling molecules traverse the endocytic pathway makes a significant contribution to downstream output. Modulation of the core endocytic machinery facilitates differential uptake of individual cargoes. Clathrin-coated pits are a major entry portal where assembled clathrin forms a lattice around invaginating buds that have captured endocytic cargo. Clathrin assembles into triskelia composed of three clathrin heavy chains and associated clathrin light chains (CLCs). Despite the identification of clathrin-coated pits at the cell surface over 30 years ago, the functions of CLCs in endocytosis have been elusive. In this work, we identify a novel role for CLCs in the regulated endocytosis of specific cargoes. Small interfering RNA-mediated knockdown of either CLCa or CLCb inhibits the uptake of GPCRs. Moreover, we demonstrate that phosphorylation of Ser204 in CLCb is required for efficient endocytosis of a subset of GPCRs and identify G protein-coupled receptor kinase 2 (GRK2) as a kinase that can phosphorylate CLCb on Ser204. Overexpression of CLCb(S204A) specifically inhibits the endocytosis of those GPCRs whose endocytosis is GRK2-dependent. Together, these results indicate that CLCb phosphorylation acts as a discriminator for the endocytosis of specific GPCRs. Copyright © 2012 Elsevier Ltd. All rights reserved.

  1. Inhibition of clathrin by pitstop 2 activates the spindle assembly checkpoint and induces cell death in dividing HeLa cancer cells

    Directory of Open Access Journals (Sweden)

    Smith Charlotte M

    2013-01-01

    Full Text Available Abstract Background During metaphase clathrin stabilises the mitotic spindle kinetochore(K-fibres. Many anti-mitotic compounds target microtubule dynamics. Pitstop 2™ is the first small molecule inhibitor of clathrin terminal domain and inhibits clathrin-mediated endocytosis. We investigated its effects on a second function for clathrin in mitosis. Results Pitstop 2 did not impair clathrin recruitment to the spindle but disrupted its function once stationed there. Pitstop 2 trapped HeLa cells in metaphase through loss of mitotic spindle integrity and activation of the spindle assembly checkpoint, phenocopying clathrin depletion and aurora A kinase inhibition. Conclusions Pitstop 2 is therefore a new tool for investigating clathrin spindle dynamics. Pitstop 2 reduced viability in dividing HeLa cells, without affecting dividing non-cancerous NIH3T3 cells, suggesting that clathrin is a possible novel anti-mitotic drug target.

  2. Epsin 1 is involved in recruitment of ubiquitinated EGF receptors into clathrin-coated pits

    DEFF Research Database (Denmark)

    Kazazic, Maja; Bertelsen, Vibeke; Pedersen, Ketil Winther

    2008-01-01

    . Furthermore, RNAi-mediated knock down of epsin 1 was found to inhibit internalization of the EGFR, while having no effect on endocytosis of the transferrin receptor. Additionally, upon knock down of epsin 1, translocation of the EGFR to central parts of clathrin-coated pits was inhibited. This supports...

  3. HIV-1 Nef hijacks clathrin coats by stabilizing AP-1:Arf1 polygons.

    Science.gov (United States)

    Shen, Qing-Tao; Ren, Xuefeng; Zhang, Rui; Lee, Il-Hyung; Hurley, James H

    2015-10-23

    The lentiviruses HIV and simian immunodeficiency virus (SIV) subvert intracellular membrane traffic as part of their replication cycle. The lentiviral Nef protein helps viruses evade innate and adaptive immune defenses by hijacking the adaptor protein 1 (AP-1) and AP-2 clathrin adaptors. We found that HIV-1 Nef and the guanosine triphosphatase Arf1 induced trimerization and activation of AP-1. Here we report the cryo-electron microscopy structures of the Nef- and Arf1-bound AP-1 trimer in the active and inactive states. A central nucleus of three Arf1 molecules organizes the trimers. We combined the open trimer with a known dimer structure and thus predicted a hexagonal assembly with inner and outer faces that bind the membranes and clathrin, respectively. Hexagons were directly visualized and the model validated by reconstituting clathrin cage assembly. Arf1 and Nef thus play interconnected roles in allosteric activation, cargo recruitment, and coat assembly, revealing an unexpectedly intricate organization of the inner AP-1 layer of the clathrin coat. Copyright © 2015, American Association for the Advancement of Science.

  4. Clathrin Heavy Chain Is Important for Viability, Oviposition, Embryogenesis and, Possibly, Systemic RNAi Response in the Predatory Mite Metaseiulus occidentalis

    Science.gov (United States)

    Wu, Ke; Hoy, Marjorie A.

    2014-01-01

    Clathrin heavy chain has been shown to be important for viability, embryogenesis, and RNA interference (RNAi) in arthropods such as Drosophila melanogaster. However, the functional roles of clathrin heavy chain in chelicerate arthropods, such as the predatory mite Metaseiulus occidentalis, remain unknown. We previously showed that dsRNA ingestion, followed by feeding on spider mites, induced systemic and robust RNAi in M. occidentalis females. In the current study, we performed a loss-of-function analysis of the clathrin heavy chain gene in M. occidentalis using RNAi. We showed that ingestion of clathrin heavy chain dsRNA by M. occidentalis females resulted in gene knockdown and reduced longevity. In addition, clathrin heavy chain dsRNA treatment almost completely abolished oviposition by M. occidentalis females and the few eggs produced did not hatch. Finally, we demonstrated that clathrin heavy chain gene knockdown in M. occidentalis females significantly reduced a subsequent RNAi response induced by ingestion of cathepsin L dsRNA. The last finding suggests that clathrin heavy chain may be involved in systemic RNAi responses mediated by orally delivered dsRNAs in M. occidentalis. PMID:25329675

  5. Equine arteritis virus is delivered to an acidic compartment of host cells via clathrin-dependent endocytosis

    International Nuclear Information System (INIS)

    Nitschke, Matthias; Korte, Thomas; Tielesch, Claudia; Ter-Avetisyan, Gohar; Tuennemann, Gisela; Cardoso, M. Cristina; Veit, Michael; Herrmann, Andreas

    2008-01-01

    Equine arteritis virus (EAV) is an enveloped, positive-stranded RNA virus belonging to the family Arteriviridae. Infection by EAV requires the release of the viral genome by fusion with the respective target membrane of the host cell. We have investigated the entry pathway of EAV into Baby Hamster Kindey cells (BHK). Infection of cells assessed by the plaque reduction assay was strongly inhibited by substances which interfere with clathrin-dependent endocytosis and by lysosomotropic compounds. Furthermore, infection of BHK cells was suppressed when clathrin-dependent endocytosis was inhibited by expression of antisense RNA of the clathrin-heavy chain before infection. These results strongly suggest that EAV is taken up via clathrin-dependent endocytosis and is delivered to acidic endosomal compartments

  6. Epidermal Growth Factor Enhances Cellular Uptake of Polystyrene Nanoparticles by Clathrin-Mediated Endocytosis.

    Science.gov (United States)

    Phuc, Le Thi Minh; Taniguchi, Akiyoshi

    2017-06-19

    The interaction between nanoparticles and cells has been studied extensively, but most research has focused on the effect of various nanoparticle characteristics, such as size, morphology, and surface charge, on the cellular uptake of nanoparticles. In contrast, there have been very few studies to assess the influence of cellular factors, such as growth factor responses, on the cellular uptake efficiency of nanoparticles. The aim of this study was to clarify the effects of epidermal growth factor (EGF) on the uptake efficiency of polystyrene nanoparticles (PS NPs) by A431 cells, a human carcinoma epithelial cell line. The results showed that EGF enhanced the uptake efficiency of A431 cells for PS NPs. In addition, inhibition and localization studies of PS NPs and EGF receptors (EGFRs) indicated that cellular uptake of PS NPs is related to the binding of EGF-EGFR complex and PS NPs. Different pathways are used to enter the cells depending on the presence or absence of EGF. In the presence of EGF, cellular uptake of PS NPs is via clathrin-mediated endocytosis, whereas, in the absence of EGF, uptake of PS NPs does not involve clathrin-mediated endocytosis. Our findings indicate that EGF enhances cellular uptake of PS NPs by clathrin-mediated endocytosis. This result could be important for developing safe nanoparticles and their safe use in medical applications.

  7. Epidermal Growth Factor Enhances Cellular Uptake of Polystyrene Nanoparticles by Clathrin-Mediated Endocytosis

    Directory of Open Access Journals (Sweden)

    Le Thi Minh Phuc

    2017-06-01

    Full Text Available The interaction between nanoparticles and cells has been studied extensively, but most research has focused on the effect of various nanoparticle characteristics, such as size, morphology, and surface charge, on the cellular uptake of nanoparticles. In contrast, there have been very few studies to assess the influence of cellular factors, such as growth factor responses, on the cellular uptake efficiency of nanoparticles. The aim of this study was to clarify the effects of epidermal growth factor (EGF on the uptake efficiency of polystyrene nanoparticles (PS NPs by A431 cells, a human carcinoma epithelial cell line. The results showed that EGF enhanced the uptake efficiency of A431 cells for PS NPs. In addition, inhibition and localization studies of PS NPs and EGF receptors (EGFRs indicated that cellular uptake of PS NPs is related to the binding of EGF–EGFR complex and PS NPs. Different pathways are used to enter the cells depending on the presence or absence of EGF. In the presence of EGF, cellular uptake of PS NPs is via clathrin-mediated endocytosis, whereas, in the absence of EGF, uptake of PS NPs does not involve clathrin-mediated endocytosis. Our findings indicate that EGF enhances cellular uptake of PS NPs by clathrin-mediated endocytosis. This result could be important for developing safe nanoparticles and their safe use in medical applications.

  8. Morphological changes of plasma membrane and protein assembly during clathrin-mediated endocytosis

    Science.gov (United States)

    Yoshida, Aiko; Sakai, Nobuaki; Uekusa, Yoshitsugu; Imaoka, Yuka; Itagaki, Yoshitsuna; Suzuki, Yuki

    2018-01-01

    Clathrin-mediated endocytosis (CME) proceeds through a series of morphological changes of the plasma membrane induced by a number of protein components. Although the spatiotemporal assembly of these proteins has been elucidated by fluorescence-based techniques, the protein-induced morphological changes of the plasma membrane have not been fully clarified in living cells. Here, we visualize membrane morphology together with protein localizations during CME by utilizing high-speed atomic force microscopy (HS-AFM) combined with a confocal laser scanning unit. The plasma membrane starts to invaginate approximately 30 s after clathrin starts to assemble, and the aperture diameter increases as clathrin accumulates. Actin rapidly accumulates around the pit and induces a small membrane swelling, which, within 30 s, rapidly covers the pit irreversibly. Inhibition of actin turnover abolishes the swelling and induces a reversible open–close motion of the pit, indicating that actin dynamics are necessary for efficient and irreversible pit closure at the end of CME. PMID:29723197

  9. Cathepsin X Cleaves Profilin 1 C-Terminal Tyr139 and Influences Clathrin-Mediated Endocytosis.

    Directory of Open Access Journals (Sweden)

    Urša Pečar Fonović

    Full Text Available Cathepsin X, a cysteine carboxypeptidase, is upregulated in several types of cancer. Its molecular target in tumor cells is profilin 1, a known tumor suppressor and regulator of actin cytoskeleton dynamics. Cathepsin X cleaves off the C-terminal Tyr139 of profilin 1, affecting binding of poly-L-proline ligands and, consequently, tumor cell migration and invasion. Profilin 1 with mutations at the C-terminus, transiently expressed in prostate cancer cells PC-3, showed that Tyr139 is important for proper function of profilin 1 as a tumor suppressor. Cleaving off Tyr139 prevents the binding of clathrin, a poly-L-proline ligand involved in endocytosis. More profilin 1-clathrin complexes were present in PC-3 cells when cathepsin X was inhibited by its specific inhibitor AMS36 or silenced by siRNA. As a consequence, the endocytosis of FITC-labeled dextran and transferrin conjugate was significantly increased. These results constitute the first report of the regulation of clathrin-mediated endocytosis in tumor cells through proteolytic processing of profilin 1.

  10. Cathepsin X Cleaves Profilin 1 C-Terminal Tyr139 and Influences Clathrin-Mediated Endocytosis

    Science.gov (United States)

    Pečar Fonović, Urša; Kos, Janko

    2015-01-01

    Cathepsin X, a cysteine carboxypeptidase, is upregulated in several types of cancer. Its molecular target in tumor cells is profilin 1, a known tumor suppressor and regulator of actin cytoskeleton dynamics. Cathepsin X cleaves off the C-terminal Tyr139 of profilin 1, affecting binding of poly-L-proline ligands and, consequently, tumor cell migration and invasion. Profilin 1 with mutations at the C-terminus, transiently expressed in prostate cancer cells PC-3, showed that Tyr139 is important for proper function of profilin 1 as a tumor suppressor. Cleaving off Tyr139 prevents the binding of clathrin, a poly-L-proline ligand involved in endocytosis. More profilin 1—clathrin complexes were present in PC-3 cells when cathepsin X was inhibited by its specific inhibitor AMS36 or silenced by siRNA. As a consequence, the endocytosis of FITC-labeled dextran and transferrin conjugate was significantly increased. These results constitute the first report of the regulation of clathrin-mediated endocytosis in tumor cells through proteolytic processing of profilin 1. PMID:26325675

  11. Heterologous activation of protein kinase C stimulates phosphorylation of delta-opioid receptor at serine 344, resulting in beta-arrestin- and clathrin-mediated receptor internalization

    DEFF Research Database (Denmark)

    Xiang, B; Yu, G H; Guo, J

    2001-01-01

    The purpose of the current study is to investigate the effect of opioid-independent, heterologous activation of protein kinase C (PKC) on the responsiveness of opioid receptor and the underlying molecular mechanisms. Our result showed that removing the C terminus of delta opioid receptor (DOR......) containing six Ser/Thr residues abolished both DPDPE- and phorbol 12-myristate 13-acetate (PMA)-induced DOR phosphorylation. The phosphorylation levels of DOR mutants T352A, T353A, and T358A/T361A/S363S were comparable to that of the wild-type DOR, whereas S344G substitution blocked PMA-induced receptor......, and ionomycin resulted in DOR internalization that required phosphorylation of Ser-344. Expression of dominant negative beta-arrestin and hypertonic sucrose treatment blocked PMA-induced DOR internalization, suggesting that PKC mediates DOR internalization via a beta-arrestin- and clathrin-dependent mechanism...

  12. Image averaging of flexible fibrous macromolecules: the clathrin triskelion has an elastic proximal segment.

    Science.gov (United States)

    Kocsis, E; Trus, B L; Steer, C J; Bisher, M E; Steven, A C

    1991-08-01

    We have developed computational techniques that allow image averaging to be applied to electron micrographs of filamentous molecules that exhibit tight and variable curvature. These techniques, which involve straightening by cubic-spline interpolation, image classification, and statistical analysis of the molecules' curvature properties, have been applied to purified brain clathrin. This trimeric filamentous protein polymerizes, both in vivo and in vitro, into a wide range of polyhedral structures. Contrasted by low-angle rotary shadowing, dissociated clathrin molecules appear as distinctive three-legged structures, called "triskelions" (E. Ungewickell and D. Branton (1981) Nature 289, 420). We find triskelion legs to vary from 35 to 62 nm in total length, according to an approximately bell-shaped distribution (mu = 51.6 nm). Peaks in averaged curvature profiles mark hinges or sites of enhanced flexibility. Such profiles, calculated for each length class, show that triskelion legs are flexible over their entire lengths. However, three curvature peaks are observed in every case: their locations define a proximal segment of systematically increasing length (14.0-19.0 nm), a mid-segment of fixed length (approximately 12 nm), and a rather variable end-segment (11.6-19.5 nm), terminating in a hinge just before the globular terminal domain (approximately 7.3 nm diameter). Thus, two major factors contribute to the overall variability in leg length: (1) stretching of the proximal segment and (2) stretching of the end-segment and/or scrolling of the terminal domain. The observed elasticity of the proximal segment may reflect phosphorylation of the clathrin light chains.

  13. Kinetics of cellular uptake of viruses and nanoparticles via clathrin-mediated endocytosis

    Science.gov (United States)

    Banerjee, Anand; Berezhkovskii, Alexander; Nossal, Ralph

    2016-02-01

    Several viruses exploit clathrin-mediated endocytosis to gain entry into host cells. This process is also used extensively in biomedical applications to deliver nanoparticles (NPs) to diseased cells. The internalization of these nano-objects is controlled by the assembly of a clathrin-containing protein coat on the cytoplasmic side of the plasma membrane, which drives the invagination of the membrane and the formation of a cargo-containing endocytic vesicle. Current theoretical models of receptor-mediated endocytosis of viruses and NPs do not explicitly take coat assembly into consideration. In this paper we study cellular uptake of viruses and NPs with a focus on coat assembly. We characterize the internalization process by the mean time between the binding of a particle to the membrane and its entry into the cell. Using a coarse-grained model which maps the stochastic dynamics of coat formation onto a one-dimensional random walk, we derive an analytical formula for this quantity. A study of the dependence of the mean internalization time on NP size shows that there is an upper bound above which this time becomes extremely large, and an optimal size at which it attains a minimum. Our estimates of these sizes compare well with experimental data. We also study the sensitivity of the obtained results on coat parameters to identify factors which significantly affect the internalization kinetics.

  14. NECAPs are negative regulators of the AP2 clathrin adaptor complex.

    Science.gov (United States)

    Beacham, Gwendolyn M; Partlow, Edward A; Lange, Jeffrey J; Hollopeter, Gunther

    2018-01-18

    Eukaryotic cells internalize transmembrane receptors via clathrin-mediated endocytosis, but it remains unclear how the machinery underpinning this process is regulated. We recently discovered that membrane-associated muniscin proteins such as FCHo and SGIP initiate endocytosis by converting the AP2 clathrin adaptor complex to an open, active conformation that is then phosphorylated (Hollopeter et al., 2014). Here we report that loss of ncap-1 , the sole C. elegans gene encoding an adaptiN Ear-binding Coat-Associated Protein (NECAP), bypasses the requirement for FCHO-1. Biochemical analyses reveal AP2 accumulates in an open, phosphorylated state in ncap-1 mutant worms, suggesting NECAPs promote the closed, inactive conformation of AP2. Consistent with this model, NECAPs preferentially bind open and phosphorylated forms of AP2 in vitro and localize with constitutively open AP2 mutants in vivo. NECAPs do not associate with phosphorylation-defective AP2 mutants, implying that phosphorylation precedes NECAP recruitment. We propose NECAPs function late in endocytosis to inactivate AP2. © 2018, Beacham et al.

  15. New Insights to Clathrin and Adaptor Protein 2 for the Design and Development of Therapeutic Strategies

    Directory of Open Access Journals (Sweden)

    Ebbe Toftgaard Poulsen

    2015-12-01

    Full Text Available The Amyloid Precursor Protein (APP has been extensively studied for its role as the precursor of the β-amyloid protein (Aβ in Alzheimer’s disease (AD. However, our understanding of the normal function of APP is still patchy. Emerging evidence indicates that a dysfunction in APP trafficking and degradation can be responsible for neuronal deficits and progressive degeneration in humans. We recently reported that the Y682 mutation in the 682YENPTY687 domain of APP affects its binding to specific adaptor proteins and leads to its anomalous trafficking, to defects in the autophagy machinery and to neuronal degeneration. In order to identify adaptors that influence APP function, we performed pull-down experiments followed by quantitative mass spectrometry (MS on hippocampal tissue extracts of three month-old mice incubated with either the 682YENPTY687 peptide, its mutated form, 682GENPTY687 or its phosphorylated form, 682pYENPTY687. Our experiments resulted in the identification of two proteins involved in APP internalization and trafficking: Clathrin heavy chain (hc and its Adaptor Protein 2 (AP-2. Overall our results consolidate and refine the importance of Y682 in APP normal functions from an animal model of premature aging and dementia. Additionally, they open the perspective to consider Clathrin hc and AP-2 as potential targets for the design and development of new therapeutic strategies.

  16. MUC1 intra-cellular trafficking is clathrin, dynamin, and rab5 dependent

    International Nuclear Information System (INIS)

    Liu Xiaolong; Yuan Zhenglong; Chung, Maureen

    2008-01-01

    MUC1, a transmembrane glycoprotein, is abnormally over-expressed in most human adenocarcinomas. MUC1 association with cytoplasmic cell signal regulators and nuclear accumulation are important for its tumor related activities. Little is known about how MUC1 translocates from the cell membrane to the cytoplasm. In this study, live cell imaging was used to study MUC1 intracellular trafficking. The interaction between EGFR and MUC1 was mapped by FRET analysis and EGF stimulated MUC1 endocytosis was observed directly through live cell imaging. MUC1-CT endocytosis was clathrin and dynamin dependent. Rab5 over-expression resulted in decreased cell membrane localization of MUC1, with accumulation of MUC1 endocytic vesicles in the peri-nuclear region. Conversely, over-expression of a Rab5 dominant negative mutant (S34N) resulted in redistribution of MUC1 from the peri-nuclear region to the cytoplasm. Collectively, these results indicated that MUC1 intra-cellular trafficking occurs through a regulated process that was stimulated by direct EGFR and MUC1 interaction, mediated by clathrin coated pits that were dynamin dependent and regulated by Rab5

  17. Clathrin to Lipid Raft-Endocytosis via Controlled Surface Chemistry and Efficient Perinuclear Targeting of Nanoparticle.

    Science.gov (United States)

    Chakraborty, Atanu; Jana, Nikhil R

    2015-09-17

    Nanoparticle interacts with live cells depending on their surface chemistry, enters into cell via endocytosis, and is commonly trafficked to an endosome/lysozome that restricts subcellular targeting options. Here we show that nanoparticle surface chemistry can be tuned to alter their cell uptake mechanism and subcellular trafficking. Quantum dot based nanoprobes of 20-30 nm hydrodynamic diameters have been synthesized with tunable surface charge (between +15 mV to -25 mV) and lipophilicity to influence their cellular uptake processes and subcellular trafficking. It is observed that cationic nanoprobe electrostatically interacts with cell membrane and enters into cell via clathrin-mediated endocytosis. At lower surface charge (between +10 mV to -10 mV), the electrostatic interaction with cell membrane becomes weaker, and additional lipid raft endocytosis is initiated. If a lipophilic functional group is introduced on a weakly anionic nanoparticle surface, the uptake mechanism shifts to predominant lipid raft-mediated endocytosis. In particular, the zwitterionic-lipophilic nanoprobe has the unique advantage as it weakly interacts with anionic cell membrane, migrates toward lipid rafts for interaction through lipophilic functional group, and induces lipid raft-mediated endocytosis. While predominate or partial clathrin-mediated entry traffics most of the nanoprobes to lysozome, predominate lipid raft-mediated entry traffics them to perinuclear region, particularly to the Golgi apparatus. This finding would guide in designing appropriate nanoprobe for subcellular targeting and delivery.

  18. Three-dimensional, Computer-tomographic Analysis of Membrane Proteins (TrkA, caveolin, clathrin) in PC12 Cells

    International Nuclear Information System (INIS)

    Nishida, Tomoki; Arii, Tatsuo; Takaoka, Akio; Yoshimura, Ryoichi; Endo, Yasuhisa

    2007-01-01

    Signaling of nerve growth factor (NGF) and its receptor (TrkA) promotes neuronal differentiation, synapse formation and survival. It has been known that the complex of NGF and TrkA is internalized into the cytoplasm and transported for further signal transduction, but the ultrastructural information of this process is virtually unknown. In order to clarify the relationship between the internalization of TrkA and the membrane-associated proteins (caveolin and clathrin), the localization and three-dimensional structures of those proteins were examined with computer tomography of high voltage electron microscopy in PC12 cells. TrkA immunoreactivity was found only at definite areas in the plasma membrane, as ring and cluster structures. Its 3D image indicated that those cluster structures contained small pits, which did not appear to be typical caveolae in size and shape. 3D images of clathrin and caveolin-1 immunoreactivities indicated that the formation of those small pits was associated with clathrin, but not with caveolin-1. Caveolin-1 immunoreactivity was found as a mesh-like structure just beneath the plasma membrane. These results suggest that clathrin rather than caveolin is mainly involved in the process of TrkA internalization, at least in differentiated PC12 cells

  19. The Ebola virus glycoprotein mediates entry via a non-classical dynamin-dependent macropinocytic pathway

    International Nuclear Information System (INIS)

    Mulherkar, Nirupama; Raaben, Matthijs; Torre, Juan Carlos de la; Whelan, Sean P.; Chandran, Kartik

    2011-01-01

    Ebola virus (EBOV) has been reported to enter cultured cell lines via a dynamin-2-independent macropinocytic pathway or clathrin-mediated endocytosis. The route(s) of productive EBOV internalization into physiologically relevant cell types remain unexplored, and viral-host requirements for this process are incompletely understood. Here, we use electron microscopy and complementary chemical and genetic approaches to demonstrate that the viral glycoprotein, GP, induces macropinocytic uptake of viral particles into cells. GP's highly-glycosylated mucin domain is dispensable for virus-induced macropinocytosis, arguing that interactions between other sequences in GP and the host cell surface are responsible. Unexpectedly, we also found a requirement for the large GTPase dynamin-2, which is proposed to be dispensable for several types of macropinocytosis. Our results provide evidence that EBOV uses an atypical dynamin-dependent macropinocytosis-like entry pathway to enter Vero cells, adherent human peripheral blood-derived monocytes, and a mouse dendritic cell line.

  20. Structure of clathrin-coated vesicles from small-angle scattering experiments

    DEFF Research Database (Denmark)

    Pedersen, J.S.

    1993-01-01

    Previously published small-angle neutron and X-ray scattering data from coated vesicles, reassembled coats, and stripped vesicles have been analyzed in terms of one common model. The neutron data sets include contrast variation measurements at three different D2O solvent concentrations. The model...... used for interpreting the data has spherical symmetry and explicitly takes into account polydispersity, which is described by a Gaussian distribution. A constant thickness of the clathrin coats is assumed. The fitting of the model shows that the coated vesicles consist of a low-density outer protein....... Thus, the membrane and the high-density protein shell overlap in space, which shows that the lipid membrane contains protein. The molecular mass of the average particle is 27 x 10(6) Da. The coated vesicles consist, on average, of approximately 85% protein and 15% lipids. About 40% of the protein mass...

  1. Interaction with epsin 1 regulates the constitutive clathrin-dependent internalization of ErbB3.

    Science.gov (United States)

    Szymanska, Monika; Fosdahl, Anne Marthe; Raiborg, Camilla; Dietrich, Markus; Liestøl, Knut; Stang, Espen; Bertelsen, Vibeke

    2016-06-01

    In contrast to other members of the EGF receptor family, ErbB3 is constitutively internalized in a clathrin-dependent manner. Previous studies have shown that ErbB3 does not interact with the coated pit localized adaptor complex 2 (AP-2), and that ErbB3 lacks two AP-2 interacting internalization signals identified in the EGF receptor. Several other clathrin-associated sorting proteins which may recruit cargo into coated pits have, however, been identified, and the study was performed to identify adaptors needed for constitutive internalization of ErbB3. A high-throughput siRNA screen was used to identify adaptor proteins needed for internalization of ErbB3. Upon knock-down of candidate proteins internalization of ErbB3 was identified using an antibody-based internalization assay combined with automatic fluorescence microscopy. Among 29 candidates only knock-down of epsin 1 turned out to inhibit ErbB3. Epsin 1 has ubiquitin interacting motifs (UIMs) and we show that ErbB3 interacts with an epsin 1 deletion mutant containing these UIMs. In support of an ErbB3-epsin 1 UIM dependent interaction, we show that ErbB3 is constitutively ubiquitinated, but that both ubiquitination and the ErbB3-epsin 1 interaction increase upon ligand binding. Altogether the results are consistent with a model whereby both constitutive and ligand-induced internalization of ErbB3 are regulated through interaction with epsin 1. Internalization is an important regulator of growth factor receptor mediated signaling and the current study identify mechanisms regulating plasma membrane turnover of ErbB3. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Ultrasound Microbubble Treatment Enhances Clathrin-Mediated Endocytosis and Fluid-Phase Uptake through Distinct Mechanisms.

    Directory of Open Access Journals (Sweden)

    Farnaz Fekri

    Full Text Available Drug delivery to tumors is limited by several factors, including drug permeability of the target cell plasma membrane. Ultrasound in combination with microbubbles (USMB is a promising strategy to overcome these limitations. USMB treatment elicits enhanced cellular uptake of materials such as drugs, in part as a result of sheer stress and formation of transient membrane pores. Pores formed upon USMB treatment are rapidly resealed, suggesting that other processes such as enhanced endocytosis may contribute to the enhanced material uptake by cells upon USMB treatment. How USMB regulates endocytic processes remains incompletely understood. Cells constitutively utilize several distinct mechanisms of endocytosis, including clathrin-mediated endocytosis (CME for the internalization of receptor-bound macromolecules such as Transferrin Receptor (TfR, and distinct mechanism(s that mediate the majority of fluid-phase endocytosis. Tracking the abundance of TfR on the cell surface and the internalization of its ligand transferrin revealed that USMB acutely enhances the rate of CME. Total internal reflection fluorescence microscopy experiments revealed that USMB treatment altered the assembly of clathrin-coated pits, the basic structural units of CME. In addition, the rate of fluid-phase endocytosis was enhanced, but with delayed onset upon USMB treatment relative to the enhancement of CME, suggesting that the two processes are distinctly regulated by USMB. Indeed, vacuolin-1 or desipramine treatment prevented the enhancement of CME but not of fluid phase endocytosis upon USMB, suggesting that lysosome exocytosis and acid sphingomyelinase, respectively, are required for the regulation of CME but not fluid phase endocytosis upon USMB treatment. These results indicate that USMB enhances both CME and fluid phase endocytosis through distinct signaling mechanisms, and suggest that strategies for potentiating the enhancement of endocytosis upon USMB treatment may

  3. Interferon-inducible transmembrane proteins of the innate immune response act as membrane organizers by influencing clathrin and v-ATPase localization and function.

    Science.gov (United States)

    Wee, Yin Shen; Roundy, Kirstin M; Weis, Janis J; Weis, John H

    2012-12-01

    The innate response interferon-inducible transmembrane (Ifitm) proteins have been characterized as influencing proliferation, signaling complexes and restricting virus infections. Treatment of cells lacking these proteins (IfitmDel) with IFN-β resulted in the loss of clathrin from membrane compartments and the inhibition of clathrin-mediated phagocytosis, suggesting a molecular interaction between clathrin and Ifitm proteins. The pH of endosomes of IfitmDel cells, with or without IFN activation, was neutralized, suggesting the function of the vacular ATPase proton pumps in such cells was compromised. Co-immunoprecipitation of Ifitm3 with Atp6v0b demonstrated a direct interaction between the Ifitm proteins and the v-ATPase. These data suggest that the Ifitm proteins help stabilize v-ATPase complexes in cellular membranes which, in turn, facilitates the appropriate subcellular localization of clathrin.

  4. The epsins define a family of proteins that interact with components of the clathrin coat and contain a new protein module

    DEFF Research Database (Denmark)

    Rosenthal, J A; Chen, H; Slepnev, V I

    1999-01-01

    Epsin (epsin 1) is an interacting partner for the EH domain-containing region of Eps15 and has been implicated in conjunction with Eps15 in clathrin-mediated endocytosis. We report here the characterization of a similar protein (epsin 2), which we have cloned from human and rat brain libraries. E...... fluorescent protein-epsin 2 mislocalizes components of the clathrin coat and inhibits clathrin-mediated endocytosis. The epsins define a new protein family implicated in membrane dynamics at the cell surface.......Epsin (epsin 1) is an interacting partner for the EH domain-containing region of Eps15 and has been implicated in conjunction with Eps15 in clathrin-mediated endocytosis. We report here the characterization of a similar protein (epsin 2), which we have cloned from human and rat brain libraries...

  5. Phospholipase D is involved in the formation of Golgi associated clathrin coated vesicles in human parotid duct cells.

    Directory of Open Access Journals (Sweden)

    Lorena Brito de Souza

    Full Text Available Phospholipase D (PLD has been implicated in many cellular functions, such as vesicle trafficking, exocytosis, differentiation, and proliferation. The aim of this study was to characterize the role of PLD in HSY cells, a human cell line originating from the intercalated duct of the parotid gland. As the function and intracellular localization of PLD varies according to cell type, initially, the intracellular localization of PLD1 and PLD2 was determined. By immunofluorescence, PLD1 and PLD2 both showed a punctate cytoplasmic distribution with extensive co-localization with TGN-46. PLD1 was also found in the nucleus, while PLD2 was associated with the plasma membrane. Treatment of cells with the primary alcohol 1-butanol inhibits the hydrolysis of phosphatidylcoline by PLD thereby suppressing phosphatidic acid (PA production. In untreated HSY cells, there was only a slight co-localization of PLD with the clathrin coated vesicles. When HSY cells were incubated with 1-butanol the total number of clathrin coated vesicles increased, especially in the juxtanuclear region and the co-localization of PLD with the clathrin coated vesicles was augmented. Transmission electron microscopy confirmed that the number of Golgi-associated coated vesicles was greater. Treatment with 1-butanol also affected the Golgi apparatus, increasing the volume of the Golgi saccules. The decrease in PA levels after treatment with 1-butanol likewise resulted in an accumulation of enlarged lysosomes in the perinuclear region. Therefore, in HSY cells PLD appears to be involved in the formation of Golgi associated clathrin coated vesicles as well as in the structural maintenance of the Golgi apparatus.

  6. Clathrin-dependent internalization, signaling, and metabolic processing of guanylyl cyclase/natriuretic peptide receptor-A.

    Science.gov (United States)

    Somanna, Naveen K; Mani, Indra; Tripathi, Satyabha; Pandey, Kailash N

    2018-04-01

    Cardiac hormones, atrial and brain natriuretic peptides (ANP and BNP), have pivotal roles in renal hemodynamics, neuroendocrine signaling, blood pressure regulation, and cardiovascular homeostasis. Binding of ANP and BNP to the guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA) induces rapid internalization and trafficking of the receptor via endolysosomal compartments, with concurrent generation of cGMP. However, the mechanisms of the endocytotic processes of NPRA are not well understood. The present study, using 125 I-ANP binding assay and confocal microscopy, examined the function of dynamin in the internalization of NPRA in stably transfected human embryonic kidney-293 (HEK-293) cells. Treatment of recombinant HEK-293 cells with ANP time-dependently accelerated the internalization of receptor from the cell surface to the cell interior. However, the internalization of ligand-receptor complexes of NPRA was drastically decreased by the specific inhibitors of clathrin- and dynamin-dependent receptor internalization, almost 85% by monodansylcadaverine, 80% by chlorpromazine, and 90% by mutant dynamin, which are specific blockers of endocytic vesicle formation. Visualizing the internalization of NPRA and enhanced GFP-tagged NPRA in HEK-293 cells by confocal microscopy demonstrated the formation of endocytic vesicles after 5 min of ANP treatment; this effect was blocked by the inhibitors of clathrin and by mutant dynamin construct. Our results suggest that NPRA undergoes internalization via clathrin-mediated endocytosis as part of its normal itinerary, including trafficking, signaling, and metabolic degradation.

  7. Cholera toxin entry into pig enterocytes occurs via a lipid raft- and clathrin-dependent mechanism

    DEFF Research Database (Denmark)

    Hansen, Gert H; Dalskov, Stine-Mathilde; Rasmussen, Christina Rehné

    2005-01-01

    The small intestinal brush border is composed of lipid raft microdomains, but little is known about their role in the mechanism whereby cholera toxin gains entry into the enterocyte. The present work characterized the binding of cholera toxin B subunit (CTB) to the brush border and its internaliz......The small intestinal brush border is composed of lipid raft microdomains, but little is known about their role in the mechanism whereby cholera toxin gains entry into the enterocyte. The present work characterized the binding of cholera toxin B subunit (CTB) to the brush border and its...... accompanied the toxin internalization whereas no formation of caveolae was observed. CTB was strongly associated with the buoyant, detergent-insoluble fraction of microvillar membranes. Neither CTB's raft association nor uptake via clathrin-coated pits was affected by methyl-beta-cyclodextrin, indicating...... that membrane cholesterol is not required for toxin binding and entry. The ganglioside GM(1) is known as the receptor for CTB, but surprisingly the toxin also bound to sucrase-isomaltase and coclustered with this glycosidase in apical membrane pits. CTB binds to lipid rafts of the brush border...

  8. The translocation of fullerenic nanoparticles into lysosome via the pathway of clathrin-mediated endocytosis

    International Nuclear Information System (INIS)

    Li Wei; Chen Chunying; Ye Chang; Zhao Yuliang; Chen Zhen; Meng Huan; Gao Yuxi; Yuan Hui; Xing Genmei; Zhao Feng; Chai Zhifang; Wei Taotao; Zhang Xujia; Yang Fuyu; Lao Fang; Han Dong; Tang Xianhua; Zhang Yingge

    2008-01-01

    Manufactured fullerene nanoparticles easily enter into cells and hence have been rapidly developed for biomedical uses. However, it is generally unknown which route the nanoparticles undergo when crossing cell membranes and where they localize to the intracellular compartments. Herein we have used both microscopic imaging and biological techniques to explore the processes of [C 60 (C(COOH) 2 ) 2 ] n nanoparticles across cellular membranes and their intracellular translocation in 3T3 L1 and RH-35 living cells. The fullerene nanoparticles are quickly internalized by the cells and then routed to the cytoplasm with punctate localization. Upon entering the cell, they are synchronized to lysosome-like vesicles. The [C 60 (C(COOH) 2 ) 2 ] n nanoparticles entering cells are mainly via endocytosis with time-, temperature- and energy-dependent manners. The cellular uptake of [C 60 (C(COOH) 2 ) 2 ] n nanoparticles was found to be clathrin-mediated but not caveolae-mediated endocytosis. The endocytosis mechanism and the subcellular target location provide key information for the better understanding and predicting of the biomedical function of fullerene nanoparticles inside cells

  9. Clathrin heavy chain 1 is required for spindle assembly and chromosome congression in mouse oocytes.

    Science.gov (United States)

    Zhao, Jie; Wang, Lu; Zhou, Hong-Xia; Liu, Li; Lu, Angeleem; Li, Guang-Peng; Schatten, Heide; Liang, Cheng-Guang

    2013-10-01

    Clathrin heavy chain 1 (CLTC) has been considered a “moonlighting protein” which acts in membrane trafficking during interphase and in stabilizing spindle fibers during mitosis. However, its roles in meiosis, especially in mammalian oocyte maturation, remain unclear. This study investigated CLTC expression and function in spindle formation and chromosome congression during mouse oocyte meiotic maturation. Our results showed that the expression level of CLTC increased after germinal vesicle breakdown (GVBD) and peaked in the M phase. Immunostaining results showed CLTC distribution throughout the cytoplasm in a cell cycle-dependent manner. Appearance and disappearance of CLTC along with β-tubulin (TUBB) could be observed during spindle dynamic changes. To explore the relationship between CLTC and microtubule dynamics, oocytes at metaphase were treated with taxol or nocodazole. CLTC colocalized with TUBB at the enlarged spindle and with cytoplasmic asters after taxol treatment; it disassembled and distributed into the cytoplasm along with TUBB after nocodazole treatment. Disruption of CLTC function using stealth siRNA caused a decreased first polar body extrusion rate and extensive spindle formation and chromosome congression defects. Taken together, these results show that CLTC plays an important role in spindle assembly and chromosome congression through a microtubule correlation mechanism during mouse oocyte maturation.

  10. Cancer cell-selective, clathrin-mediated endocytosis of aptamer decorated nanoparticles

    Science.gov (United States)

    Engelberg, Shira; Modrejewski, Julia; Walter, Johanna G.; Livney, Yoav D.; Assaraf, Yehuda G.

    2018-01-01

    Lung cancer is the leading cause of cancer mortality worldwide, resulting in 88% deaths of all diagnosed patients. Hence, novel therapeutic modalities are urgently needed. Single-stranded oligonucleotide-based aptamers (APTs) are excellent ligands for tumor cell targeting. However, the molecular mechanisms underlying their internalization into living cells have been poorly studied. Towards the application of APTs for active drug targeting to cancer cells, we herein studied the mechanism underlying S15-APT internalization into human non-small cell lung cancer A549 cells. We thus delineated the mode of entry of a model nanomedical system based on quantum dots (QDs) decorated with S15-APTs as a selective targeting moiety for uptake by A549 cells. These APT-decorated QDs displayed selective binding to, and internalization by target A549 cells, but not by normal human bronchial epithelial BEAS2B, cervical carcinoma (HeLa) and colon adenocarcinoma CaCo-2 cells, hence demonstrating high specificity. Flow cytometric analysis revealed a remarkably low dissociation constant of S15-APTs-decorated QDs to A549 cells (Kd = 13.1 ± 1.6 nM). Through the systematic application of a series of established inhibitors of known mechanisms of endocytosis, we show that the uptake of S15-APTs proceeds via a classical clathrin-dependent receptor-mediated endocytosis. This cancer cell-selective mode of entry could possibly be used in the future to evade plasma membrane-localized multidrug resistance efflux pumps, thereby overcoming an important mechanism of cancer multidrug resistance. PMID:29765515

  11. Genetic Deletion of the Clathrin Adaptor GGA3 Reduces Anxiety and Alters GABAergic Transmission.

    Directory of Open Access Journals (Sweden)

    Kendall R Walker

    Full Text Available Golgi-localized γ-ear-containing ARF binding protein 3 (GGA3 is a monomeric clathrin adaptor that has been shown to regulate the trafficking of the Beta-site APP-cleaving enzyme (BACE1, which is required for production of the Alzheimer's disease (AD-associated amyloid βpeptide. Our previous studies have shown that BACE1 is degraded via the lysosomal pathway and that depletion of GGA3 results in increased BACE1 levels and activity owing to impaired lysosomal trafficking and degradation. We further demonstrated the role of GGA3 in the regulation of BACE1 in vivo by showing that BACE1 levels are increased in the brain of GGA3 null mice. We report here that GGA3 deletion results in novelty-induced hyperactivity and decreased anxiety-like behaviors. Given the pivotal role of GABAergic transmission in the regulation of anxiety-like behaviors, we performed electrophysiological recordings in hippocampal slices and found increased phasic and decreased tonic inhibition in the dentate gyrus granule cells (DGGC. Moreover, we found that the number of inhibitory synapses is increased in the dentate gyrus of GGA3 null mice in further support of the electrophysiological data. Thus, the increased GABAergic transmission is a leading candidate mechanism underlying the reduced anxiety-like behaviors observed in GGA3 null mice. All together these findings suggest that GGA3 plays a key role in GABAergic transmission. Since BACE1 levels are elevated in the brain of GGA3 null mice, it is possible that at least some of these phenotypes are a consequence of increased processing of BACE1 substrates.

  12. Genetic Deletion of the Clathrin Adaptor GGA3 Reduces Anxiety and Alters GABAergic Transmission.

    Science.gov (United States)

    Walker, Kendall R; Modgil, Amit; Albrecht, David; Lomoio, Selene; Haydon, Philip G; Moss, Stephen J; Tesco, Giuseppina

    2016-01-01

    Golgi-localized γ-ear-containing ARF binding protein 3 (GGA3) is a monomeric clathrin adaptor that has been shown to regulate the trafficking of the Beta-site APP-cleaving enzyme (BACE1), which is required for production of the Alzheimer's disease (AD)-associated amyloid βpeptide. Our previous studies have shown that BACE1 is degraded via the lysosomal pathway and that depletion of GGA3 results in increased BACE1 levels and activity owing to impaired lysosomal trafficking and degradation. We further demonstrated the role of GGA3 in the regulation of BACE1 in vivo by showing that BACE1 levels are increased in the brain of GGA3 null mice. We report here that GGA3 deletion results in novelty-induced hyperactivity and decreased anxiety-like behaviors. Given the pivotal role of GABAergic transmission in the regulation of anxiety-like behaviors, we performed electrophysiological recordings in hippocampal slices and found increased phasic and decreased tonic inhibition in the dentate gyrus granule cells (DGGC). Moreover, we found that the number of inhibitory synapses is increased in the dentate gyrus of GGA3 null mice in further support of the electrophysiological data. Thus, the increased GABAergic transmission is a leading candidate mechanism underlying the reduced anxiety-like behaviors observed in GGA3 null mice. All together these findings suggest that GGA3 plays a key role in GABAergic transmission. Since BACE1 levels are elevated in the brain of GGA3 null mice, it is possible that at least some of these phenotypes are a consequence of increased processing of BACE1 substrates.

  13. Internalisation of membrane progesterone receptor-α after treatment with progesterone: Potential involvement of a clathrin-dependent pathway.

    Science.gov (United States)

    Foster, Helen; Reynolds, Alan; Stenbeck, Gudrun; Dong, Jing; Thomas, Peter; Karteris, Emmanouil

    2010-01-01

    Internalisation and recycling of seven trans-membrane domain receptors is a critical regulatory event for their signalling. The mechanism(s) by which membrane progesterone receptor-α (mPRα) number is regulated on the cell surface is unclear. In this study, we investigated the cellular distribution of mPRα and mechanisms of mPRα trafficking using a cell line derived from a primary culture of human myometrial cells (M11) as an experimental model. RT-PCR and immunofluorescent analysis demonstrated expression of mPRα in M11 cells with mPRα primarily distributed on the cell surface under basal conditions. For the first time, plasma membrane localisation of mPRα was confirmed using immuno-gold transmission electron microscopy. Stimulation of M11 cells with progesterone (P4, 100 nM) resulted in internalisation of mPRα from the plasma membrane to the cytoplasm (10 min) and subsequent partial translocation back to the cell surface (20 min). We investigated potential endocytotic pathways involved in trafficking of mPRα after its internalisation. Partial co-localisation of clathrin with mPRα was obvious after 10 min of P4 treatment. Of note, chlorpromazine (inhibitor of clathrin-mediated pathway) inhibited the endocytosis of mPRα, whereas treatment with nystatin (inhibitor of caveolae-mediated pathway) did not affect internalisation. Collectively, these data suggest that mPRα is expressed on the cell surface of M11 cells and undergoes endocytosis after P4 stimulation primarily via a clathrin-mediated pathway.

  14. Simian hemorrhagic fever virus cell entry is dependent on CD163 and uses a clathrin-mediated endocytosis-like pathway.

    Science.gov (United States)

    Caì, Yíngyún; Postnikova, Elena N; Bernbaum, John G; Yú, Shu Qìng; Mazur, Steven; Deiuliis, Nicole M; Radoshitzky, Sheli R; Lackemeyer, Matthew G; McCluskey, Adam; Robinson, Phillip J; Haucke, Volker; Wahl-Jensen, Victoria; Bailey, Adam L; Lauck, Michael; Friedrich, Thomas C; O'Connor, David H; Goldberg, Tony L; Jahrling, Peter B; Kuhn, Jens H

    2015-01-01

    Simian hemorrhagic fever virus (SHFV) causes a severe and almost uniformly fatal viral hemorrhagic fever in Asian macaques but is thought to be nonpathogenic for humans. To date, the SHFV life cycle is almost completely uncharacterized on the molecular level. Here, we describe the first steps of the SHFV life cycle. Our experiments indicate that SHFV enters target cells by low-pH-dependent endocytosis. Dynamin inhibitors, chlorpromazine, methyl-β-cyclodextrin, chloroquine, and concanamycin A dramatically reduced SHFV entry efficiency, whereas the macropinocytosis inhibitors EIPA, blebbistatin, and wortmannin and the caveolin-mediated endocytosis inhibitors nystatin and filipin III had no effect. Furthermore, overexpression and knockout study and electron microscopy results indicate that SHFV entry occurs by a dynamin-dependent clathrin-mediated endocytosis-like pathway. Experiments utilizing latrunculin B, cytochalasin B, and cytochalasin D indicate that SHFV does not hijack the actin polymerization pathway. Treatment of target cells with proteases (proteinase K, papain, α-chymotrypsin, and trypsin) abrogated entry, indicating that the SHFV cell surface receptor is a protein. Phospholipases A2 and D had no effect on SHFV entry. Finally, treatment of cells with antibodies targeting CD163, a cell surface molecule identified as an entry factor for the SHFV-related porcine reproductive and respiratory syndrome virus, diminished SHFV replication, identifying CD163 as an important SHFV entry component. Simian hemorrhagic fever virus (SHFV) causes highly lethal disease in Asian macaques resembling human illness caused by Ebola or Lassa virus. However, little is known about SHFV's ecology and molecular biology and the mechanism by which it causes disease. The results of this study shed light on how SHFV enters its target cells. Using electron microscopy and inhibitors for various cellular pathways, we demonstrate that SHFV invades cells by low-pH-dependent, actin-independent

  15. Clathrin-Mediated Auxin Efflux and Maxima Regulate Hypocotyl Hook Formation and Light-Stimulated Hook Opening in Arabidopsis.

    Science.gov (United States)

    Yu, Qinqin; Zhang, Ying; Wang, Juan; Yan, Xu; Wang, Chao; Xu, Jian; Pan, Jianwei

    2016-01-04

    The establishment of auxin maxima by PIN-FORMED 3 (PIN3)- and AUXIN RESISTANT 1/LIKE AUX1 (LAX) 3 (AUX1/LAX3)-mediated auxin transport is essential for hook formation in Arabidopsis hypocotyls. Until now, however, the underlying regulatory mechanism has remained poorly understood. Here, we show that loss of function of clathrin light chain CLC2 and CLC3 genes enhanced auxin maxima and thereby hook curvature, alleviated the inhibitory effect of auxin overproduction on auxin maxima and hook curvature, and delayed blue light-stimulated auxin maxima reduction and hook opening. Moreover, pharmacological experiments revealed that auxin maxima formation and hook curvature in clc2 clc3 were sensitive to auxin efflux inhibitors 1-naphthylphthalamic acid and 2,3,5-triiodobenzoic acid but not to the auxin influx inhibitor 1-naphthoxyacetic acid. Live-cell imaging analysis further uncovered that loss of CLC2 and CLC3 function impaired PIN3 endocytosis and promoted its lateralization in the cortical cells but did not affect AUX1 localization. Taken together, these results suggest that clathrin regulates auxin maxima and thereby hook formation through modulating PIN3 localization and auxin efflux, providing a novel mechanism that integrates developmental signals and environmental cues to regulate plant skotomorphogenesis and photomorphogenesis. Copyright © 2016 The Author. Published by Elsevier Inc. All rights reserved.

  16. Are Independent Probes Truly Independent?

    Science.gov (United States)

    Camp, Gino; Pecher, Diane; Schmidt, Henk G.; Zeelenberg, Rene

    2009-01-01

    The independent cue technique has been developed to test traditional interference theories against inhibition theories of forgetting. In the present study, the authors tested the critical criterion for the independence of independent cues: Studied cues not presented during test (and unrelated to test cues) should not contribute to the retrieval…

  17. Architecture of clathrin fullerene cages reflects a geometric constraint--the head-to-tail exclusion rule--and a preference for asymmetry.

    Science.gov (United States)

    Schein, Stan

    2009-03-27

    Fullerene cages have n trivalent vertices, 12 pentagonal faces, and (n-20)/2 hexagonal faces. The smallest cage in which all of the pentagons are surrounded by hexagons and thus isolated from each other has 60 vertices and is shaped like a soccer ball. The protein clathrin self-assembles into fullerene cages of a variety of sizes and shapes, including smaller ones with adjacent pentagons as well as larger ones, but the variety is limited. To explain the range of clathrin architecture and how these fullerene cages self-assemble, we proposed a hypothesis, the "head-to-tail exclusion rule" (the "Rule"). Of the 5769 small clathrin cage isomers with n< or =60 vertices and adjacent pentagons, the Rule permits just 15, three identified in 1976 and 12 others. A "weak version" of the Rule permits another 99. Based on cryo-electron tomography, Cheng et al. reported six raw clathrin fullerene cages. One was among the three identified in 1976. Here, (1) we identify the remaining five. (2) Four are new and are among the 12 others permitted by the Rule. (3) One, also new, is among the 99 weak version cages. (4) Of particular note, none of the remaining 5565 excluded cages has been identified. These findings provide powerful experimental confirmation of the Rule and the principle on which it is based. (5) Surprisingly, the newly identified clathrin cages are among the least symmetric of those permitted. (6) By devising a method for counting assembly paths, (7) we show that asymmetric cages can be assembled by larger numbers of paths, thus providing a kinetic explanation for the prevalence of asymmetric cages. (8) Finally, we show that operation during cage growth of the Rule greatly increases the likelihood of producing a closed fullerene cage, specifically one of those permitted, but efficient assembly still appears to require internal remodeling.

  18. Caenorhabditis elegans reveals a FxNPxY-independent low-density lipoprotein receptor internalization mechanism mediated by epsin1

    Science.gov (United States)

    Kang, Yuan-Lin; Yochem, John; Bell, Leslie; Sorensen, Erika B.; Chen, Lihsia; Conner, Sean D.

    2013-01-01

    Low-density lipoprotein receptor (LDLR) internalization clears cholesterol-laden LDL particles from circulation in humans. Defects in clathrin-dependent LDLR endocytosis promote elevated serum cholesterol levels and can lead to atherosclerosis. However, our understanding of the mechanisms that control LDLR uptake remains incomplete. To identify factors critical to LDLR uptake, we pursued a genome-wide RNA interference screen using Caenorhabditis elegans LRP-1/megalin as a model for LDLR transport. In doing so, we discovered an unanticipated requirement for the clathrin-binding endocytic adaptor epsin1 in LDLR endocytosis. Epsin1 depletion reduced LDLR internalization rates in mammalian cells, similar to the reduction observed following clathrin depletion. Genetic and biochemical analyses of epsin in C. elegans and mammalian cells uncovered a requirement for the ubiquitin-interaction motif (UIM) as critical for receptor transport. As the epsin UIM promotes the internalization of some ubiquitinated receptors, we predicted LDLR ubiquitination as necessary for endocytosis. However, engineered ubiquitination-impaired LDLR mutants showed modest internalization defects that were further enhanced with epsin1 depletion, demonstrating epsin1-mediated LDLR endocytosis is independent of receptor ubiquitination. Finally, we provide evidence that epsin1-mediated LDLR uptake occurs independently of either of the two documented internalization motifs (FxNPxY or HIC) encoded within the LDLR cytoplasmic tail, indicating an additional internalization mechanism for LDLR. PMID:23242996

  19. Herpes simplex virus internalization into epithelial cells requires Na+/H+ exchangers and p21-activated kinases but neither clathrin- nor caveolin-mediated endocytosis.

    Science.gov (United States)

    Devadas, Deepika; Koithan, Thalea; Diestel, Randi; Prank, Ute; Sodeik, Beate; Döhner, Katinka

    2014-11-01

    Herpes simplex virus 1 (HSV-1) is an alphaherpesvirus that has been reported to infect some epithelial cell types by fusion at the plasma membrane but others by endocytosis. To determine the molecular mechanisms of productive HSV-1 cell entry, we perturbed key endocytosis host factors using specific inhibitors, RNA interference (RNAi), or overexpression of dominant negative proteins and investigated their effects on HSV-1 infection in the permissive epithelial cell lines Vero, HeLa, HEp-2, and PtK2. HSV-1 internalization required neither endosomal acidification nor clathrin- or caveolin-mediated endocytosis. In contrast, HSV-1 gene expression and internalization were significantly reduced after treatment with 5-(N-ethyl-N-isopropyl)amiloride (EIPA). EIPA blocks the activity of Na(+)/H(+) exchangers, which are plasma membrane proteins implicated in all forms of macropinocytosis. HSV-1 internalization furthermore required the function of p21-activated kinases that contribute to macropinosome formation. However, in contrast to some forms of macropinocytosis, HSV-1 did not enlist the activities of protein kinase C (PKC), tyrosine kinases, C-terminal binding protein 1, or dynamin to activate its internalization. These data suggest that HSV-1 depends on Na(+)/H(+) exchangers and p21-activated kinases either for macropinocytosis or for local actin rearrangements required for fusion at the plasma membrane or subsequent passage through the actin cortex underneath the plasma membrane. After initial replication in epithelial cells, herpes simplex viruses (HSVs) establish latent infections in neurons innervating these regions. Upon primary infection and reactivation from latency, HSVs cause many human skin and neurological diseases, particularly in immunocompromised hosts, despite the availability of effective antiviral drugs. Many viruses use macropinocytosis for virus internalization, and many host factors mediating this entry route have been identified, although the

  20. Independent preferences

    DEFF Research Database (Denmark)

    Vind, Karl

    1991-01-01

    A simple mathematical result characterizing a subset of a product set is proved and used to obtain additive representations of preferences. The additivity consequences of independence assumptions are obtained for preferences which are not total or transitive. This means that most of the economic ...... theory based on additive preferences - expected utility, discounted utility - has been generalized to preferences which are not total or transitive. Other economic applications of the theorem are given...

  1. Phospho-dependent binding of the clathrin AP2 adaptor complex to GABAA receptors regulates the efficacy of inhibitory synaptic transmission

    OpenAIRE

    Kittler, Josef T.; Chen, Guojun; Honing, Stephan; Bogdanov, Yury; McAinsh, Kristina; Arancibia-Carcamo, I. Lorena; Jovanovic, Jasmina N.; Pangalos, Menelas N.; Haucke, Volker; Yan, Zhen; Moss, Stephen J.

    2005-01-01

    The efficacy of synaptic inhibition depends on the number of γ-aminobutyric acid type A receptors (GABAARs) expressed on the cell surface of neurons. The clathrin adaptor protein 2 (AP2) complex is a critical regulator of GABAAR endocytosis and, hence, surface receptor number. Here, we identify a previously uncharacterized atypical AP2 binding motif conserved within the intracellular domains of all GABAAR β subunit isoforms. This AP2 binding motif (KTHLRRRSSQLK in the β3 subunit) incorporates...

  2. C-terminal of human histamine H1 receptors regulates their agonist-induced clathrin-mediated internalization and G-protein signaling.

    Science.gov (United States)

    Hishinuma, Shigeru; Nozawa, Hiroki; Akatsu, Chizuru; Shoji, Masaru

    2016-11-01

    It has been suggested that the agonist-induced internalization of G-protein-coupled receptors from the cell surface into intracellular compartments regulates cellular responsiveness. We previously reported that G q/11 -protein-coupled human histamine H 1 receptors internalized via clathrin-dependent mechanisms upon stimulation with histamine. However, the molecular determinants of H 1 receptors responsible for agonist-induced internalization remain unclear. In this study, we evaluated the roles of the intracellular C-terminal of human histamine H 1 receptors tagged with hemagglutinin (HA) at the N-terminal in histamine-induced internalization in Chinese hamster ovary cells. The histamine-induced internalization was evaluated by the receptor binding assay with [ 3 H]mepyramine and confocal immunofluorescence microscopy with an anti-HA antibody. We found that histamine-induced internalization was inhibited under hypertonic conditions or by pitstop, a clathrin terminal domain inhibitor, but not by filipin or nystatin, disruptors of the caveolar structure and function. The histamine-induced internalization was also inhibited by truncation of a single amino acid, Ser487, located at the end of the intracellular C-terminal of H 1 receptors, but not by its mutation to alanine. In contrast, the receptor-G-protein coupling, which was evaluated by histamine-induced accumulation of [ 3 H]inositol phosphates, was potentiated by truncation of Ser487, but was lost by its mutation to alanine. These results suggest that the intracellular C-terminal of human H 1 receptors, which only comprises 17 amino acids (Cys471-Ser487), plays crucial roles in both clathrin-dependent internalization of H 1 receptors and G-protein signaling, in which truncation of Ser487 and its mutation to alanine are revealed to result in biased signaling toward activation of G-proteins and clathrin-mediated internalization, respectively. © 2016 International Society for Neurochemistry.

  3. Protein kinase A-induced internalization of Slack channels from the neuronal membrane occurs by adaptor protein-2/clathrin-mediated endocytosis.

    Science.gov (United States)

    Gururaj, Sushmitha; Evely, Katherine M; Pryce, Kerri D; Li, Jun; Qu, Jun; Bhattacharjee, Arin

    2017-11-24

    The sodium-activated potassium (K Na ) channel Kcnt1 (Slack) is abundantly expressed in nociceptor (pain-sensing) neurons of the dorsal root ganglion (DRG), where they transmit the large outward conductance I KNa and arbitrate membrane excitability. Slack channel expression at the DRG membrane is necessary for their characteristic firing accommodation during maintained stimulation, and reduced membrane channel density causes hyperexcitability. We have previously shown that in a pro-inflammatory state, a decrease in membrane channel expression leading to reduced Slack-mediated I KNa expression underlies DRG neuronal sensitization. An important component of the inflammatory milieu, PKA internalizes Slack channels from the DRG membrane, reduces I KNa , and produces DRG neuronal hyperexcitability when activated in cultured primary DRG neurons. Here, we show that this PKA-induced retrograde trafficking of Slack channels also occurs in intact spinal cord slices and that it is carried out by adaptor protein-2 (AP-2) via clathrin-mediated endocytosis. We provide mass spectrometric and biochemical evidence of an association of native neuronal AP-2 adaptor proteins with Slack channels, facilitated by a dileucine motif housed in the cytoplasmic Slack C terminus that binds AP-2. By creating a competitive peptide blocker of AP-2-Slack binding, we demonstrated that this interaction is essential for clathrin recruitment to the DRG membrane, Slack channel endocytosis, and DRG neuronal hyperexcitability after PKA activation. Together, these findings uncover AP-2 and clathrin as players in Slack channel regulation. Given the significant role of Slack in nociceptive neuronal excitability, the AP-2 clathrin-mediated endocytosis trafficking mechanism may enable targeting of peripheral and possibly, central neuronal sensitization. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  4. A highly phosphorylated subpopulation of insulin-like growth factor II/mannose 6-phosphate receptors is concentrated in a clathrin-enriched plasma membrane fraction

    International Nuclear Information System (INIS)

    Corvera, S.; Folander, K.; Clairmont, K.B.; Czech, M.P.

    1988-01-01

    Insulin-like growth factor II (IGF-II)/mannose 6-phosphate (Man-6-P) receptors immunoprecipitated from purified plasma membranes of 32 P-labeled rat adipocytes are markedly heterogenous in their phosphorylation state. Approximately 80% of the plasma membrane receptors are solubilized in 1% (vol/vol) Triton X-100 and are phosphorylated on serine residues at a stoichiometry of ∼ 0.1-0.2 mol of phosphate per mol of receptor. In contrast, 15-20% of the receptors are Triton X-100-insoluble and are phosphorylated on serine and threonine residues at ∼ 4 or 5 mol of phosphate per mol of receptor. This Triton X-100-insoluble membrane subfraction contains only 5% of the total plasma membrane protein and yet contains all of the clathrin heavy chain associated with plasma membrane. Based on the relative yields of protein in the detergent-insoluble material, IGF-II/Man-6-P receptors are concentrated ∼ 3-fold in this clathrin-enriched subfraction. Taken together, these results indicate that insulin decreases the phosphorylation state of a highly phosphorylated subpopulation of IGF-II/Man-6-P receptors on the plasma membrane. In addition, insulin action may prevent the concentration of these receptors in a clathrin-enriched membrane subfraction

  5. Cellular entry of G3.5 poly (amido amine) dendrimers by clathrin- and dynamin-dependent endocytosis promotes tight junctional opening in intestinal epithelia.

    Science.gov (United States)

    Goldberg, Deborah S; Ghandehari, Hamidreza; Swaan, Peter W

    2010-08-01

    This study investigates the mechanisms of G3.5 poly (amido amine) dendrimer cellular uptake, intracellular trafficking, transepithelial transport and tight junction modulation in Caco-2 cells in the context of oral drug delivery. Chemical inhibitors blocking clathrin-, caveolin- and dynamin-dependent endocytosis pathways were used to investigate the mechanisms of dendrimer cellular uptake and transport across Caco-2 cells using flow cytometry and confocal microscopy. Dendrimer cellular uptake was found to be dynamin-dependent and was reduced by both clathrin and caveolin endocytosis inhibitors, while transepithelial transport was only dependent on dynamin- and clathrin-mediated endocytosis. Dendrimers were quickly trafficked to the lysosomes after 15 min of incubation and showed increased endosomal accumulation at later time points, suggesting saturation of this pathway. Dendrimers were unable to open tight junctions in cell monolayers treated with dynasore, a selective inhibitor of dynamin, confirming that dendrimer internalization promotes tight junction modulation. G3.5 PAMAM dendrimers take advantage of several receptor-mediated endocytosis pathways for cellular entry in Caco-2 cells. Dendrimer internalization by dynamin-dependent mechanisms promotes tight junction opening, suggesting that dendrimers act on intracellular cytoskeletal proteins to modulate tight junctions, thus catalyzing their own transport via the paracellular route.

  6. Independent Directors

    DEFF Research Database (Denmark)

    Ringe, Wolf-Georg

    2013-01-01

    This paper re-evaluates the corporate governance concept of ‘board independence’ against the disappointing experiences during the 2007-08 financial crisis. Independent or outside directors had long been seen as an essential tool to improve the monitoring role of the board. Yet the crisis revealed...... that they did not prevent firms' excessive risk taking; further, these directors sometimes showed serious deficits in understanding the business they were supposed to control, and remained passive in addressing structural problems. A closer look reveals that under the surface of seemingly unanimous consensus...

  7. Mesenchymal Stem Cells Inhibit Transmission of α-Synuclein by Modulating Clathrin-Mediated Endocytosis in a Parkinsonian Model

    Directory of Open Access Journals (Sweden)

    Se Hee Oh

    2016-02-01

    Full Text Available Ample evidence suggests that α-synuclein is released from cells and propagated from one area of the brain to others via cell-to-cell transmission. In terms of their prion-like behavior, α-synuclein propagation plays key roles in the pathogenesis and progression of α-synucleinopathies. Using α-synuclein-enriched models, we show that mesenchymal stem cells (MSCs inhibited α-synuclein transmission by blocking the clathrin-mediated endocytosis of extracellular α-synuclein via modulation of the interaction with N-methyl-D-aspartate receptors, which led to a prosurvival effect on cortical and dopaminergic neurons with functional improvement of motor deficits in α-synuclein-enriched models. Furthermore, we identify that galectin-1, a soluble factor derived from MSCs, played an important role in the transmission control of aggregated α-synuclein in these models. The present data indicated that MSCs exert neuroprotective properties through inhibition of extracellular α-synuclein transmission, suggesting that the property of MSCs may act as a disease-modifying therapy in subjects with α-synucleinopathies.

  8. Clathrin-mediated endocytosis and transcytosis of enterotoxigenic Escherichia coli F4 fimbriae in porcine intestinal epithelial cells.

    Science.gov (United States)

    Rasschaert, Kristien; Devriendt, Bert; Favoreel, Herman; Goddeeris, Bruno M; Cox, Eric

    2010-10-15

    Enterotoxigenic Escherichia coli (ETEC) cause severe diarrhea in neonatal and recently weaned piglets. Previously, we demonstrated that oral immunization of F4 receptor positive piglets with purified F4 fimbriae induces a protective F4-specific intestinal immune response. However, in F4 receptor negative animals no F4-specific immune response can be elicited, indicating that the induction of an F4-specific mucosal immune response upon oral immunisation is receptor-dependent. Although F4 fimbriae undergo transcytosis across the intestinal epithelium in vivo, the endocytosis pathways used remain unknown. In the present study, we characterized the internalization of F4 fimbriae in the porcine intestinal epithelial cell line IPEC-J2. The results in the present study demonstrate that F4 fimbriae are internalized through a clathrin-dependent pathway. Furthermore, our results suggest that F4 fimbriae are transcytosed across differentiated IPEC-J2 cells. This receptor-dependent transcytosis of F4 fimbriae may explain the immunogenicity of these fimbriae upon oral administration in vivo. (c) 2010 Elsevier B.V. All rights reserved.

  9. Peptide aptamers as new tools to modulate clathrin-mediated internalisation — inhibition of MT1-MMP internalisation

    Directory of Open Access Journals (Sweden)

    Ferrigno Paul

    2010-07-01

    Full Text Available Abstract Background Peptide aptamers are combinatorial protein reagents that bind to targets with a high specificity and a strong affinity thus providing a molecular tool kit for modulating the function of their targets in vivo. Results Here we report the isolation of a peptide aptamer named swiggle that interacts with the very short (21 amino acid long intracellular domain of membrane type 1-metalloproteinase (MT1-MMP, a key cell surface protease involved in numerous and crucial physiological and pathological cellular events. Expression of swiggle in mammalian cells was found to increase the cell surface expression of MT1-MMP by impairing its internalisation. Swiggle interacts with the LLY573 internalisation motif of MT1-MMP intracellular domain, thus disrupting the interaction with the μ2 subunit of the AP-2 internalisation complex required for endocytosis of the protease. Interestingly, swiggle-mediated inhibition of MT1-MMP clathrin-mediated internalisation was also found to promote MT1-MMP-mediated cell migration. Conclusions Taken together, our results provide further evidence that peptide aptamers can be used to dissect molecular events mediated by individual protein domains, in contrast to the pleiotropic effects of RNA interference techniques.

  10. Peptide aptamers as new tools to modulate clathrin-mediated internalisation--inhibition of MT1-MMP internalisation.

    Science.gov (United States)

    Wickramasinghe, Rochana D; Ko Ferrigno, Paul; Roghi, Christian

    2010-07-23

    Peptide aptamers are combinatorial protein reagents that bind to targets with a high specificity and a strong affinity thus providing a molecular tool kit for modulating the function of their targets in vivo. Here we report the isolation of a peptide aptamer named swiggle that interacts with the very short (21 amino acid long) intracellular domain of membrane type 1-metalloproteinase (MT1-MMP), a key cell surface protease involved in numerous and crucial physiological and pathological cellular events. Expression of swiggle in mammalian cells was found to increase the cell surface expression of MT1-MMP by impairing its internalisation. Swiggle interacts with the LLY573 internalisation motif of MT1-MMP intracellular domain, thus disrupting the interaction with the mu2 subunit of the AP-2 internalisation complex required for endocytosis of the protease. Interestingly, swiggle-mediated inhibition of MT1-MMP clathrin-mediated internalisation was also found to promote MT1-MMP-mediated cell migration. Taken together, our results provide further evidence that peptide aptamers can be used to dissect molecular events mediated by individual protein domains, in contrast to the pleiotropic effects of RNA interference techniques.

  11. Distinct CPT-induced deaths in lung cancer cells caused by clathrin-mediated internalization of CP micelles

    Science.gov (United States)

    Liu, Yu-Sheng; Cheng, Ru-You; Lo, Yu-Lun; Hsu, Chin; Chen, Su-Hwei; Chiu, Chien-Chih; Wang, Li-Fang

    2016-02-01

    We previously synthesized a chondroitin sulfate-graft-poly(ε-caprolactone) copolymer (H-CP) with a high content of poly(ε-caprolactone) (18.7 mol%), which self-assembled in water into a rod-like micelle to encapsulate hydrophobic camptothecin (CPT) in the core (micelle/CPT) for tumor-targeted drug delivery. As a result of the recognition of the micelle by CD44, the micelle/CPT entered CRL-5802 cells efficiently and released CPT efficaciously, resulting in higher tumor suppression than commercial CPT-11. In this study, H1299 cells were found to have a higher CD44 expression than CRL-5802 cells. However, the lower CD44-expressing CRL-5802 cells had a higher percentage of cell death and higher cellular uptake of the micelle/CPT than the higher CD44-expressing H1299 cells. Examination of the internalization pathway of the micelle/CPT in the presence of different endocytic chemical inhibitors showed that the CRL-5802 cells involved clathrin-mediated endocytosis, which was not found in the H1299 cells. Analysis of the cell cycle of the two cell lines exposed to the micelle/CPT revealed that the CRL-5802 cells arrested mainly in the S phase and the H1299 cells arrested mainly in the G2-M phase. A consistent result was also found in the evaluation of γ-H2AX expression, which was about three-fold higher in the CRL-5802 cells than in the H1299 cells. A near-infrared dye, IR780, was encapsulated into the micelle to observe the in vivo biodistribution of the micelle/IR780 in tumor-bearing mice. The CRL-5802 tumor showed a higher fluorescence intensity than the H1299 tumor at any tracing time after 1 h. Thus we tentatively concluded that CRL-5802 cells utilized the clathrin-mediated internalization pathway and arrested in the S phase on exposure to the micelle/CPT; all are possible reasons for the better therapeutic outcome in CRL-5802 cells than in H1299 cells.We previously synthesized a chondroitin sulfate-graft-poly(ε-caprolactone) copolymer (H-CP) with a high content of

  12. Role of adaptor proteins and clathrin in the trafficking of human kidney anion exchanger 1 (kAE1) to the cell surface.

    Science.gov (United States)

    Junking, Mutita; Sawasdee, Nunghathai; Duangtum, Natapol; Cheunsuchon, Boonyarit; Limjindaporn, Thawornchai; Yenchitsomanus, Pa-thai

    2014-07-01

    Kidney anion exchanger 1 (kAE1) plays an important role in acid-base homeostasis by mediating chloride/bicarbornate (Cl-/HCO3-) exchange at the basolateral membrane of α-intercalated cells in the distal nephron. Impaired intracellular trafficking of kAE1 caused by mutations of SLC4A1 encoding kAE1 results in kidney disease - distal renal tubular acidosis (dRTA). However, it is not known how the intracellular sorting and trafficking of kAE1 from trans-Golgi network (TGN) to the basolateral membrane occurs. Here, we studied the role of basolateral-related sorting proteins, including the mu1 subunit of adaptor protein (AP) complexes, clathrin and protein kinase D, on kAE1 trafficking in polarized and non-polarized kidney cells. By using RNA interference, co-immunoprecipitation, yellow fluorescent protein-based protein fragment complementation assays and immunofluorescence staining, we demonstrated that AP-1 mu1A, AP-3 mu1, AP-4 mu1 and clathrin (but not AP-1 mu1B, PKD1 or PKD2) play crucial roles in intracellular sorting and trafficking of kAE1. We also demonstrated colocalization of kAE1 and basolateral-related sorting proteins in human kidney tissues by double immunofluorescence staining. These findings indicate that AP-1 mu1A, AP-3 mu1, AP-4 mu1 and clathrin are required for kAE1 sorting and trafficking from TGN to the basolateral membrane of acid-secreting α-intercalated cells. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. The AP2 clathrin adaptor protein complex regulates the abundance of GLR-1 glutamate receptors in the ventral nerve cord of Caenorhabditis elegans.

    Science.gov (United States)

    Garafalo, Steven D; Luth, Eric S; Moss, Benjamin J; Monteiro, Michael I; Malkin, Emily; Juo, Peter

    2015-05-15

    Regulation of glutamate receptor (GluR) abundance at synapses by clathrin-mediated endocytosis can control synaptic strength and plasticity. We take advantage of viable, null mutations in subunits of the clathrin adaptor protein 2 (AP2) complex in Caenorhabditis elegans to characterize the in vivo role of AP2 in GluR trafficking. In contrast to our predictions for an endocytic adaptor, we found that levels of the GluR GLR-1 are decreased at synapses in the ventral nerve cord (VNC) of animals with mutations in the AP2 subunits APM-2/μ2, APA-2/α, or APS-2/σ2. Rescue experiments indicate that APM-2/μ2 functions in glr-1-expressing interneurons and the mature nervous system to promote GLR-1 levels in the VNC. Genetic analyses suggest that APM-2/μ2 acts upstream of GLR-1 endocytosis in the VNC. Consistent with this, GLR-1 accumulates in cell bodies of apm-2 mutants. However, GLR-1 does not appear to accumulate at the plasma membrane of the cell body as expected, but instead accumulates in intracellular compartments including Syntaxin-13- and RAB-14-labeled endosomes. This study reveals a novel role for the AP2 clathrin adaptor in promoting the abundance of GluRs at synapses in vivo, and implicates AP2 in the regulation of GluR trafficking at an early step in the secretory pathway. © 2015 Garafalo et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  14. Size-dependent internalisation of folate-decorated nanoparticles via the pathways of clathrin and caveolae-mediated endocytosis in ARPE-19 cells.

    Science.gov (United States)

    Langston Suen, Wai-Leung; Chau, Ying

    2014-04-01

    We aim to quantify the effect of size and degree of folate loading of folate-decorated polymeric nanoparticles (NPs) on the kinetics of cellular uptake and the selection of endocytic pathways in retinal pigment epithelium (RPE) cells. In this study, methoxy-poly(ethylene glycol)-b-polycaprolactone (mPEG-b-PCL) and folate-functionalized PEG-b-PCL were synthesized for assembling into nanoparticles with sizes ranging from 50 nm to 250 nm. These nanoparticles were internalized into ARPE-19 (human RPE cell line) via receptor-mediated endocytosis. A two-step endocytosis process mathematical model was adopted to quantify binding affinity and uptake kinetics of nanoparticles in RPE cells in uptake and inhibition studies. Nanoparticles with 100% folate loading have highest binding affinity and uptake rate in RPE cells. Maximum uptake rate (Vmax) of nanoparticles increased as the size of particles decreased from 250 nm to 50 nm. Endocytic pathway study was studied by using chlorpromazine and methyl-β-cyclodextran (MβCD), which are clathrin- and caveolae-mediated endocytosis inhibitors, respectively. Both chlorpromazine and MβCD inhibited the uptake of folate-decorated nanoparticles. Inhibition constant (Ki) and maximum uptake rate (Vmax) revealed that 50 nm and 120 nm folate-decorated nanoparticles were found to be internalized via both clathrin- and caveolae-mediated endocytosis. The 250 nm folate-decorated nanoparticles, however, were only internalized via caveolae-mediated pathway. Increased uptake rate of folate-decorated NPs into RPE cells is observed with increasing degree of folate modification. These NPs utilize both clathrin- and caveolae-mediated receptor-mediated endocytosis pathways to enter RPE cells upon size variation. The 50 nm NPs are internalized the fastest, with clathrin-mediated endocytosis as the preferred route. Uptake of 250 nm particles is the slowest and is dominated by caveolae-mediated endocytosis. © 2013 Royal Pharmaceutical

  15. Adaptor protein complex 2-mediated, clathrin-dependent endocytosis, and related gene activities, are a prominent feature during maturation stage amelogenesis.

    Science.gov (United States)

    Lacruz, Rodrigo S; Brookes, Steven J; Wen, Xin; Jimenez, Jaime M; Vikman, Susanna; Hu, Ping; White, Shane N; Lyngstadaas, S Petter; Okamoto, Curtis T; Smith, Charles E; Paine, Michael L

    2013-03-01

    Molecular events defining enamel matrix removal during amelogenesis are poorly understood. Early reports have suggested that adaptor proteins (AP) participate in ameloblast-mediated endocytosis. Enamel formation involves the secretory and maturation stages, with an increase in resorptive function during the latter. Here, using real-time PCR, we show that the expression of clathrin and adaptor protein subunits are upregulated in maturation stage rodent enamel organ cells. AP complex 2 (AP-2) is the most upregulated of the four distinct adaptor protein complexes. Immunolocalization confirms the presence of AP-2 and clathrin in ameloblasts, with strongest reactivity at the apical pole. These data suggest that the resorptive functions of enamel cells involve AP-2 mediated, clathrin-dependent endocytosis, thus implying the likelihood of specific membrane-bound receptor(s) of enamel matrix protein debris. The mRNA expression of other endocytosis-related gene products is also upregulated during maturation including: lysosomal-associated membrane protein 1 (Lamp1); cluster of differentiation 63 and 68 (Cd63 and Cd68); ATPase, H(+) transporting, lysosomal V0 subunit D2 (Atp6v0d2); ATPase, H(+) transporting, lysosomal V1 subunit B2 (Atp6v1b2); chloride channel, voltage-sensitive 7 (Clcn7); and cathepsin K (Ctsk). Immunohistologic data confirms the expression of a number of these proteins in maturation stage ameloblasts. The enamel of Cd63-null mice was also examined. Despite increased mRNA and protein expression in the enamel organ during maturation, the enamel of Cd63-null mice appeared normal. This may suggest inherent functional redundancies between Cd63 and related gene products, such as Lamp1 and Cd68. Ameloblast-like LS8 cells treated with the enamel matrix protein complex Emdogain showed upregulation of AP-2 and clathrin subunits, further supporting the existence of a membrane-bound receptor-regulated pathway for the endocytosis of enamel matrix proteins. These data

  16. Adaptor Protein Complex 2 (AP-2) Mediated, Clathrin Dependent Endocytosis, And Related Gene Activities, Are A Prominent Feature During Maturation Stage Amelogenesis

    Science.gov (United States)

    LACRUZ, Rodrigo S.; BROOKES, Steven J.; WEN, Xin; JIMENEZ, Jaime M.; VIKMAN, Susanna; HU, Ping; WHITE, Shane N.; LYNGSTADAAS, S. Petter; OKAMOTO, Curtis T.; SMITH, Charles E.; PAINE, Michael L.

    2012-01-01

    Molecular events defining enamel matrix removal during amelogenesis are poorly understood. Early reports have suggested that adaptor proteins (AP) participate in ameloblast-mediated endocytosis. Enamel formation involves the secretory and maturation stages, with an increase in resorptive function during the latter. Here, using real time PCR, we show that the expression of clathrin and adaptor protein subunits are up-regulated in maturation stage rodent enamel organ cells. AP-2 is the most up-regulated of the four distinct adaptor protein complexes. Immunolocalization confirms the presence of AP-2 and clathrin in ameloblasts with strongest reactivity at the apical pole. These data suggest that the resorptive functions of enamel cells involve AP-2 mediated, clathrin dependent endocytosis, thus implying the likelihood of a specific membrane-bound receptor(s) of enamel matrix protein debris. The mRNA expression of other endocytosis-related gene products is also up-regulated during maturation including: lysosomal-associated membrane protein 1 (Lamp1), cluster of differentiation 63 and 68 (Cd63 and Cd68), ATPase, H+ transporting, lysosomal V0 subunit D2 (Atp6v0d2), ATPase, H+ transporting, lysosomal V1 subunit B2 (Atp6v1b2), chloride channel, voltage-sensitive 7 (Clcn7) and cathepsin K (Ctsk). Immunohistological data confirms the expression of a number of these proteins in maturation stage ameloblasts. The enamel of Cd63-null mice was also examined. Despite increased mRNA and protein expression in the enamel organ during maturation, the enamel of Cd63-null mice appeared normal. This may suggest inherent functional redundancies between Cd63 and related gene products, such as Lamp1 and Cd68. Ameloblast-like LS8 cells treated with the enamel matrix protein complex Emdogain® showed up-regulation of AP-2 and clathrin subunits, further supporting the existence of a membrane-bound receptor regulated pathway for the endocytosis of enamel matrix proteins. These data together

  17. Perfluorooctanoic acid affects endocytosis involving clathrin light chain A and microRNA-133b-3p in mouse testes

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Yin; Wang, Jianshe [Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101 (China); Guo, Xuejiang [State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, PR China. (China); Yan, Shengmin [Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101 (China); Dai, Jiayin, E-mail: daijy@ioz.ac.cn [Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101 (China)

    2017-03-01

    Perfluorooctanoic acid (PFOA) is an abundant perfluoroalkyl substance widely applied in industrial and consumer products. Among its potential health hazards, testicular toxicity is of major concern. To explore the potential effect of miRNA on post-translational regulation after PFOA exposure, changes in miRNAs were detected via miRNA array. Seventeen miRNAs were differentially expressed (eight upregulated, nine downregulated) in male mouse testes after exposure to 5 mg/kg/d of PFOA for 28 d (> 1.5-fold and P < 0.05 compared with the control). Eight of these miRNAs were further selected for TaqMan qPCR analysis. Proteomic profile analysis indicated that many changed proteins after PFOA treatment, including intersectin 1 (ITSN1), serine protease inhibitor A3K (Serpina3k), and apolipoprotein a1 (APOA1), were involved in endocytosis and blood-testis barrier (BTB) processes. These changes were further verified by immunohistochemical and Western blot analyses. Endocytosis-related genes were selected for qPCR analysis, with many found to be significantly changed after PFOA treatment, including epidermal growth factor receptor pathway substrate 8 (Eps8), Eps15, cortactin, cofilin, espin, vinculin, and zyxin. We further predicted the potential interaction between changed miRNAs and proteins, which indicated that miRNAs might play a role in the post-translational regulation of gene expression after PFOA treatment in mouse testes. Among them, miR-133b-3p/clathrin light chain A (CLTA) was selected and verified in vitro by transfection and luciferase activity assay. Results showed that PFOA exposure affects endocytosis in mouse testes and that CLTA is a potential target of miR-133b-3p. - Highlights: • Endocytosis and blood-testis barrier proteins were changed after PFOA exposure. • Seventeen miRNAs were differentially expressed in testes after PFOA exposure. • MiRNAs might play a role in gene regulation in testes after PFOA exposure.CLTA is a potential target of miR-133b

  18. Perfluorooctanoic acid affects endocytosis involving clathrin light chain A and microRNA-133b-3p in mouse testes

    International Nuclear Information System (INIS)

    Lu, Yin; Wang, Jianshe; Guo, Xuejiang; Yan, Shengmin; Dai, Jiayin

    2017-01-01

    Perfluorooctanoic acid (PFOA) is an abundant perfluoroalkyl substance widely applied in industrial and consumer products. Among its potential health hazards, testicular toxicity is of major concern. To explore the potential effect of miRNA on post-translational regulation after PFOA exposure, changes in miRNAs were detected via miRNA array. Seventeen miRNAs were differentially expressed (eight upregulated, nine downregulated) in male mouse testes after exposure to 5 mg/kg/d of PFOA for 28 d (> 1.5-fold and P < 0.05 compared with the control). Eight of these miRNAs were further selected for TaqMan qPCR analysis. Proteomic profile analysis indicated that many changed proteins after PFOA treatment, including intersectin 1 (ITSN1), serine protease inhibitor A3K (Serpina3k), and apolipoprotein a1 (APOA1), were involved in endocytosis and blood-testis barrier (BTB) processes. These changes were further verified by immunohistochemical and Western blot analyses. Endocytosis-related genes were selected for qPCR analysis, with many found to be significantly changed after PFOA treatment, including epidermal growth factor receptor pathway substrate 8 (Eps8), Eps15, cortactin, cofilin, espin, vinculin, and zyxin. We further predicted the potential interaction between changed miRNAs and proteins, which indicated that miRNAs might play a role in the post-translational regulation of gene expression after PFOA treatment in mouse testes. Among them, miR-133b-3p/clathrin light chain A (CLTA) was selected and verified in vitro by transfection and luciferase activity assay. Results showed that PFOA exposure affects endocytosis in mouse testes and that CLTA is a potential target of miR-133b-3p. - Highlights: • Endocytosis and blood-testis barrier proteins were changed after PFOA exposure. • Seventeen miRNAs were differentially expressed in testes after PFOA exposure. • MiRNAs might play a role in gene regulation in testes after PFOA exposure.CLTA is a potential target of miR-133b

  19. Clathrin-dependent internalization of the angiotensin II AT₁A receptor links receptor internalization to COX-2 protein expression in rat aortic vascular smooth muscle cells.

    Science.gov (United States)

    Morinelli, Thomas A; Walker, Linda P; Velez, Juan Carlos Q; Ullian, Michael E

    2015-02-05

    The major effects of Angiotensin II (AngII) in vascular tissue are mediated by AngII AT1A receptor activation. Certain effects initiated by AT1A receptor activation require receptor internalization. In rat aortic vascular smooth muscle cells (RASMC), AngII stimulates cyclooxygenase 2 protein expression. We have previously shown this is mediated by β-arrestin-dependent receptor internalization and NF-κB activation. In this study, a specific inhibitor of clathrin-mediated endocytosis (CME), pitstop-2, was used to test the hypothesis that clathrin-dependent internalization of activated AT1A receptor mediates NF-κB activation and subsequent cyclooxygenase 2 expression. Radioligand binding assays, real time qt-PCR and immunoblotting were used to document the effects of pitstop-2 on AngII binding and signaling in RASMC. Laser scanning confocal microscopy (LSCM) was used to image pitstop-2׳s effects on AT1 receptor/GFP internalization in HEK-293 cells and p65 NF-κB nuclear localization in RASMC. Pitstop-2 significantly inhibited internalization of AT1A receptor (44.7% ± 3.1% Control vs. 13.2% ± 8.3% Pitstop-2; n=3) as determined by radioligand binding studies in RASMC. Studies utilizing AT1A receptor/GFP expressed in HEK 293 cells and LSCM confirmed these findings. Pitstop-2 significantly inhibited AngII-induced p65 NF-κB phosphorylation and nuclear localization, COX-2 message and protein expression in RASMC without altering activation of p42/44 ERK or TNFα signaling. Pitstop-2, a specific inhibitor of clathrin-mediated endocytosis, confirms that internalization of activated AT1A receptor mediates AngII activation of cyclooxygenase 2 expression in RASMC. These data provide support for additional intracellular signaling pathways activated through β-arrestin mediated internalization of G protein-coupled receptors, such as AT1A receptors. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Host cell virus entry mediated by Australian bat lyssavirus G envelope glycoprotein occurs through a clathrin-mediated endocytic pathway that requires actin and Rab5.

    Science.gov (United States)

    Weir, Dawn L; Laing, Eric D; Smith, Ina L; Wang, Lin-Fa; Broder, Christopher C

    2014-02-27

    Australian bat lyssavirus (ABLV), a rhabdovirus of the genus Lyssavirus which circulates in both pteropid fruit bats and insectivorous bats in mainland Australia, has caused three fatal human infections, the most recent in February 2013, manifested as acute neurological disease indistinguishable from clinical rabies. Rhabdoviruses infect host cells through receptor-mediated endocytosis and subsequent pH-dependent fusion mediated by their single envelope glycoprotein (G), but the specific host factors and pathways involved in ABLV entry have not been determined. ABLV internalization into HEK293T cells was examined using maxGFP-encoding recombinant vesicular stomatitis viruses (rVSV) that express ABLV G glycoproteins. A combination of chemical and molecular approaches was used to investigate the contribution of different endocytic pathways to ABLV entry. Dominant negative Rab GTPases were used to identify the endosomal compartment utilized by ABLV to gain entry into the host cell cytosol. Here we show that ABLV G-mediated entry into HEK293T cells was significantly inhibited by the dynamin-specific inhibitor dynasore, chlorpromazine, a drug that blocks clathrin-mediated endocytosis, and the actin depolymerizing drug latrunculin B. Over expression of dominant negative mutants of Eps15 and Rab5 also significantly reduced ABLV G-mediated entry into HEK293T cells. Chemical inhibitors of caveolae-dependent endocytosis and macropinocytosis and dominant negative mutants of Rab7 and Rab11 had no effect on ABLV entry. The predominant pathway utilized by ABLV for internalization into HEK293T cells is clathrin-and actin-dependent. The requirement of Rab5 for productive infection indicates that ABLV G-mediated fusion occurs within the early endosome compartment.

  1. Independence and Product Systems

    OpenAIRE

    Skeide, Michael

    2003-01-01

    Starting from elementary considerations about independence and Markov processes in classical probability we arrive at the new concept of conditional monotone independence (or operator-valued monotone independence). With the help of product systems of Hilbert modules we show that monotone conditional independence arises naturally in dilation theory.

  2. Poly-lactic acid nanoparticles (PLA-NP) promote physiological modifications in lung epithelial cells and are internalized by clathrin-coated pits and lipid rafts.

    Science.gov (United States)

    da Luz, Camila Macedo; Boyles, Matthew Samuel Powys; Falagan-Lotsch, Priscila; Pereira, Mariana Rodrigues; Tutumi, Henrique Rudolf; de Oliveira Santos, Eidy; Martins, Nathalia Balthazar; Himly, Martin; Sommer, Aniela; Foissner, Ilse; Duschl, Albert; Granjeiro, José Mauro; Leite, Paulo Emílio Corrêa

    2017-01-31

    Poly-lactic acid nanoparticles (PLA-NP) are a type of polymeric NP, frequently used as nanomedicines, which have advantages over metallic NP such as the ability to maintain therapeutic drug levels for sustained periods of time. Despite PLA-NP being considered biocompatible, data concerning alterations in cellular physiology are scarce. We conducted an extensive evaluation of PLA-NP biocompatibility in human lung epithelial A549 cells using high throughput screening and more complex methodologies. These included measurements of cytotoxicity, cell viability, immunomodulatory potential, and effects upon the cells' proteome. We used non- and green-fluorescent PLA-NP with 63 and 66 nm diameters, respectively. Cells were exposed with concentrations of 2, 20, 100 and 200 µg/mL, for 24, 48 and 72 h, in most experiments. Moreover, possible endocytic mechanisms of internalization of PLA-NP were investigated, such as those involving caveolae, lipid rafts, macropinocytosis and clathrin-coated pits. Cell viability and proliferation were not altered in response to PLA-NP. Multiplex analysis of secreted mediators revealed a low-level reduction of IL-12p70 and vascular epidermal growth factor (VEGF) in response to PLA-NP, while all other mediators assessed were unaffected. However, changes to the cells' proteome were observed in response to PLA-NP, and, additionally, the cellular stress marker miR155 was found to reduce. In dual exposures of staurosporine (STS) with PLA-NP, PLA-NP enhanced susceptibility to STS-induced cell death. Finally, PLA-NP were rapidly internalized in association with clathrin-coated pits, and, to a lesser extent, with lipid rafts. These data demonstrate that PLA-NP are internalized and, in general, tolerated by A549 cells, with no cytotoxicity and no secretion of pro-inflammatory mediators. However, PLA-NP exposure may induce modification of biological functions of A549 cells, which should be considered when designing drug delivery systems. Moreover

  3. Are Independent Fiscal Institutions Really Independent?

    Directory of Open Access Journals (Sweden)

    Slawomir Franek

    2015-08-01

    Full Text Available In the last decade the number of independent fiscal institutions (known also as fiscal councils has tripled. They play an important oversight role over fiscal policy-making in democratic societies, especially as they seek to restore public finance stability in the wake of the recent financial crisis. Although common functions of such institutions include a role in analysis of fiscal policy, forecasting, monitoring compliance with fiscal rules or costing of spending proposals, their roles, resources and structures vary considerably across countries. The aim of the article is to determine the degree of independence of such institutions based on the analysis of the independence index of independent fiscal institutions. The analysis of this index values may be useful to determine the relations between the degree of independence of fiscal councils and fiscal performance of particular countries. The data used to calculate the index values will be derived from European Commission and IMF, which collect sets of information about characteristics of activity of fiscal councils.

  4. Central Bank independence

    Directory of Open Access Journals (Sweden)

    Vasile DEDU

    2012-08-01

    Full Text Available In this paper we present the key aspects regarding central bank’s independence. Most economists consider that the factor which positively influences the efficiency of monetary policy measures is the high independence of the central bank. We determined that the National Bank of Romania (NBR has a high degree of independence. NBR has both goal and instrument independence. We also consider that the hike of NBR’s independence played an important role in the significant disinflation process, as headline inflation dropped inside the targeted band of 3% ± 1 percentage point recently.

  5. Phospho-dependent binding of the clathrin AP2 adaptor complex to GABAA receptors regulates the efficacy of inhibitory synaptic transmission.

    Science.gov (United States)

    Kittler, Josef T; Chen, Guojun; Honing, Stephan; Bogdanov, Yury; McAinsh, Kristina; Arancibia-Carcamo, I Lorena; Jovanovic, Jasmina N; Pangalos, Menelas N; Haucke, Volker; Yan, Zhen; Moss, Stephen J

    2005-10-11

    The efficacy of synaptic inhibition depends on the number of gamma-aminobutyric acid type A receptors (GABA(A)Rs) expressed on the cell surface of neurons. The clathrin adaptor protein 2 (AP2) complex is a critical regulator of GABA(A)R endocytosis and, hence, surface receptor number. Here, we identify a previously uncharacterized atypical AP2 binding motif conserved within the intracellular domains of all GABA(A)R beta subunit isoforms. This AP2 binding motif (KTHLRRRSSQLK in the beta3 subunit) incorporates the major sites of serine phosphorylation within receptor beta subunits, and phosphorylation within this site inhibits AP2 binding. Furthermore, by using surface plasmon resonance, we establish that a peptide (pepbeta3) corresponding to the AP2 binding motif in the GABA(A)R beta3 subunit binds to AP2 with high affinity only when dephosphorylated. Moreover, the pepbeta3 peptide, but not its phosphorylated equivalent (pepbeta3-phos), enhanced the amplitude of miniature inhibitory synaptic current and whole cell GABA(A)R current. These effects of pepbeta3 on GABA(A)R current were occluded by inhibitors of dynamin-dependent endocytosis supporting an action of pepbeta3 on GABA(A)R endocytosis. Therefore phospho-dependent regulation of AP2 binding to GABA(A)Rs provides a mechanism to specify receptor cell surface number and the efficacy of inhibitory synaptic transmission.

  6. Organizing Independent Student Work

    Directory of Open Access Journals (Sweden)

    Zhadyra T. Zhumasheva

    2015-03-01

    Full Text Available This article addresses issues in organizing independent student work. The author defines the term “independence”, discusses the concepts of independent learner work and independent learner work under the guidance of an instructor, proposes a classification of assignments to be done independently, and provides methodological recommendations as to the organization of independent student work. The article discusses the need for turning the student from a passive consumer of knowledge into an active creator of it, capable of formulating a problem, analyzing the ways of solving it, coming up with an optimum outcome, and proving its correctness. The preparation of highly qualified human resources is the primary condition for boosting Kazakhstan’s competitiveness. Independent student work is a means of fostering the professional competence of future specialists. The primary form of self-education is independent work.

  7. Accounting for Independent Schools.

    Science.gov (United States)

    Sonenstein, Burton

    The diversity of independent schools in size, function, and mode of operation has resulted in a considerable variety of accounting principles and practices. This lack of uniformity has tended to make understanding, evaluation, and comparison of independent schools' financial statements a difficult and sometimes impossible task. This manual has…

  8. Probabilistic conditional independence structures

    CERN Document Server

    Studeny, Milan

    2005-01-01

    Probabilistic Conditional Independence Structures provides the mathematical description of probabilistic conditional independence structures; the author uses non-graphical methods of their description, and takes an algebraic approach.The monograph presents the methods of structural imsets and supermodular functions, and deals with independence implication and equivalence of structural imsets.Motivation, mathematical foundations and areas of application are included, and a rough overview of graphical methods is also given.In particular, the author has been careful to use suitable terminology, and presents the work so that it will be understood by both statisticians, and by researchers in artificial intelligence.The necessary elementary mathematical notions are recalled in an appendix.

  9. Independent technical review, handbook

    International Nuclear Information System (INIS)

    1994-02-01

    Purpose Provide an independent engineering review of the major projects being funded by the Department of Energy, Office of Environmental Restoration and Waste Management. The independent engineering review will address questions of whether the engineering practice is sufficiently developed to a point where a major project can be executed without significant technical problems. The independent review will focus on questions related to: (1) Adequacy of development of the technical base of understanding; (2) Status of development and availability of technology among the various alternatives; (3) Status and availability of the industrial infrastructure to support project design, equipment fabrication, facility construction, and process and program/project operation; (4) Adequacy of the design effort to provide a sound foundation to support execution of project; (5) Ability of the organization to fully integrate the system, and direct, manage, and control the execution of a complex major project

  10. Independent technical review, handbook

    Energy Technology Data Exchange (ETDEWEB)

    1994-02-01

    Purpose Provide an independent engineering review of the major projects being funded by the Department of Energy, Office of Environmental Restoration and Waste Management. The independent engineering review will address questions of whether the engineering practice is sufficiently developed to a point where a major project can be executed without significant technical problems. The independent review will focus on questions related to: (1) Adequacy of development of the technical base of understanding; (2) Status of development and availability of technology among the various alternatives; (3) Status and availability of the industrial infrastructure to support project design, equipment fabrication, facility construction, and process and program/project operation; (4) Adequacy of the design effort to provide a sound foundation to support execution of project; (5) Ability of the organization to fully integrate the system, and direct, manage, and control the execution of a complex major project.

  11. Model-Independent Diffs

    DEFF Research Database (Denmark)

    Könemann, Patrick

    just contain a list of strings, one for each line, whereas the structure of models is defined by their meta models. There are tools available which are able to compute the diff between two models, e.g. RSA or EMF Compare. However, their diff is not model-independent, i.e. it refers to the models...

  12. All Those Independent Variables.

    Science.gov (United States)

    Meacham, Merle L.

    This paper presents a case study of a sixth grade remedial math class which illustrates the thesis that only the "experimental attitude," not the "experimental method," is appropriate in the classroom. The thesis is based on the fact that too many independent variables exist in a classroom situation to allow precise measurement. The case study…

  13. Bayesian Independent Component Analysis

    DEFF Research Database (Denmark)

    Winther, Ole; Petersen, Kaare Brandt

    2007-01-01

    In this paper we present an empirical Bayesian framework for independent component analysis. The framework provides estimates of the sources, the mixing matrix and the noise parameters, and is flexible with respect to choice of source prior and the number of sources and sensors. Inside the engine...

  14. Independent safety organization

    International Nuclear Information System (INIS)

    Kato, W.Y.; Weinstock, E.V.; Carew, J.F.; Cerbone, R.J.; Guppy, J.G.; Hall, R.E.; Taylor, J.H.

    1985-01-01

    Brookhaven National Laboratory has conducted a study on the need and feasibility of an independent organization to investigate significant safety events for the Office for Analysis and Evaluation of Operational Data, USNRC. The study consists of three parts: the need for an independent organization to investigate significant safety events, alternative organizations to conduct investigations, and legislative requirements. The determination of need was investigated by reviewing current NRC investigation practices, comparing aviation and nuclear industry practices, and interviewing a spectrum of representatives from the nuclear industry, the regulatory agency, and the public sector. The advantages and disadvantages of alternative independent organizations were studied, namely, an Office of Nuclear Safety headed by a director reporting to the Executive Director for Operations (EDO) of NRC; an Office of Nuclear Safety headed by a director reporting to the NRC Commissioners; a multi-member NTSB-type Nuclear Safety Board independent of the NRC. The costs associated with operating a Nuclear Safety Board were also included in the study. The legislative requirements, both new authority and changes to the existing NRC legislative authority, were studied. 134 references

  15. Quantum independent increment processes

    CERN Document Server

    Franz, Uwe

    2005-01-01

    This volume is the first of two volumes containing the revised and completed notes lectures given at the school "Quantum Independent Increment Processes: Structure and Applications to Physics". This school was held at the Alfried-Krupp-Wissenschaftskolleg in Greifswald during the period March 9 – 22, 2003, and supported by the Volkswagen Foundation. The school gave an introduction to current research on quantum independent increment processes aimed at graduate students and non-specialists working in classical and quantum probability, operator algebras, and mathematical physics. The present first volume contains the following lectures: "Lévy Processes in Euclidean Spaces and Groups" by David Applebaum, "Locally Compact Quantum Groups" by Johan Kustermans, "Quantum Stochastic Analysis" by J. Martin Lindsay, and "Dilations, Cocycles and Product Systems" by B.V. Rajarama Bhat.

  16. Quantum independent increment processes

    CERN Document Server

    Franz, Uwe

    2006-01-01

    This is the second of two volumes containing the revised and completed notes of lectures given at the school "Quantum Independent Increment Processes: Structure and Applications to Physics". This school was held at the Alfried-Krupp-Wissenschaftskolleg in Greifswald in March, 2003, and supported by the Volkswagen Foundation. The school gave an introduction to current research on quantum independent increment processes aimed at graduate students and non-specialists working in classical and quantum probability, operator algebras, and mathematical physics. The present second volume contains the following lectures: "Random Walks on Finite Quantum Groups" by Uwe Franz and Rolf Gohm, "Quantum Markov Processes and Applications in Physics" by Burkhard Kümmerer, Classical and Free Infinite Divisibility and Lévy Processes" by Ole E. Barndorff-Nielsen, Steen Thorbjornsen, and "Lévy Processes on Quantum Groups and Dual Groups" by Uwe Franz.

  17. Independent random sampling methods

    CERN Document Server

    Martino, Luca; Míguez, Joaquín

    2018-01-01

    This book systematically addresses the design and analysis of efficient techniques for independent random sampling. Both general-purpose approaches, which can be used to generate samples from arbitrary probability distributions, and tailored techniques, designed to efficiently address common real-world practical problems, are introduced and discussed in detail. In turn, the monograph presents fundamental results and methodologies in the field, elaborating and developing them into the latest techniques. The theory and methods are illustrated with a varied collection of examples, which are discussed in detail in the text and supplemented with ready-to-run computer code. The main problem addressed in the book is how to generate independent random samples from an arbitrary probability distribution with the weakest possible constraints or assumptions in a form suitable for practical implementation. The authors review the fundamental results and methods in the field, address the latest methods, and emphasize the li...

  18. International exploration by independents

    International Nuclear Information System (INIS)

    Bertagne, R.G.

    1991-01-01

    Recent industry trends indicate that the smaller US independents are looking at foreign exploration opportunities as one of the alternatives for growth in the new age of exploration. It is usually accepted that foreign finding costs per barrel are substantially lower than domestic because of the large reserve potential of international plays. To get involved overseas requires, however, an adaptation to different cultural, financial, legal, operational, and political conditions. Generally foreign exploration proceeds at a slower pace than domestic because concessions are granted by the government, or are explored in partnership with the national oil company. First, a mid- to long-term strategy, tailored to the goals and the financial capabilities of the company, must be prepared; it must be followed by an ongoing evaluation of quality prospects in various sedimentary basins, and a careful planning and conduct of the operations. To successfully explore overseas also requires the presence on the team of a minimum number of explorationists and engineers thoroughly familiar with the various exploratory and operational aspects of foreign work, having had a considerable amount of onsite experience in various geographical and climatic environments. Independents that are best suited for foreign expansion are those that have been financially successful domestically, and have a good discovery track record. When properly approached foreign exploration is well within the reach of smaller US independents and presents essentially no greater risk than domestic exploration; the reward, however, can be much larger and can catapult the company into the big leagues

  19. International exploration by independent

    International Nuclear Information System (INIS)

    Bertragne, R.G.

    1992-01-01

    Recent industry trends indicate that the smaller U.S. independents are looking at foreign exploration opportunities as one of the alternatives for growth in the new age of exploration. Foreign finding costs per barrel usually are accepted to be substantially lower than domestic costs because of the large reserve potential of international plays. To get involved in overseas exploration, however, requires the explorationist to adapt to different cultural, financial, legal, operational, and political conditions. Generally, foreign exploration proceeds at a slower pace than domestic exploration because concessions are granted by a country's government, or are explored in partnership with a national oil company. First, the explorationist must prepare a mid- to long-term strategy, tailored to the goals and the financial capabilities of the company; next, is an ongoing evaluation of quality prospects in various sedimentary basins, and careful planning and conduct of the operations. To successfully explore overseas also requires the presence of a minimum number of explorationists and engineers thoroughly familiar with the various exploratory and operational aspects of foreign work. Ideally, these team members will have had a considerable amount of on-site experience in various countries and climates. Independents best suited for foreign expansion are those who have been financially successful in domestic exploration. When properly approached, foreign exploration is well within the reach of smaller U.S. independents, and presents essentially no greater risk than domestic exploration; however, the reward can be much larger and can catapult the company into the 'big leagues.'

  20. Agent independent task planning

    Science.gov (United States)

    Davis, William S.

    1990-01-01

    Agent-Independent Planning is a technique that allows the construction of activity plans without regard to the agent that will perform them. Once generated, a plan is then validated and translated into instructions for a particular agent, whether a robot, crewmember, or software-based control system. Because Space Station Freedom (SSF) is planned for orbital operations for approximately thirty years, it will almost certainly experience numerous enhancements and upgrades, including upgrades in robotic manipulators. Agent-Independent Planning provides the capability to construct plans for SSF operations, independent of specific robotic systems, by combining techniques of object oriented modeling, nonlinear planning and temporal logic. Since a plan is validated using the physical and functional models of a particular agent, new robotic systems can be developed and integrated with existing operations in a robust manner. This technique also provides the capability to generate plans for crewmembers with varying skill levels, and later apply these same plans to more sophisticated robotic manipulators made available by evolutions in technology.

  1. International exploration by independents

    International Nuclear Information System (INIS)

    Bertagne, R.G.

    1992-01-01

    Recent industry trends indicate that the smaller U.S. independents are looking at foreign exploration opportunities as one of the alternatives for growth in the new age of exploration. The problems of communications and logistics caused by different cultures and by geographic distances must be carefully evaluated. A mid-term to long-term strategy tailored to the goals and the financial capabilities of the company should be prepared and followed by a careful planning of the operations. This paper addresses some aspects of foreign exploration that should be considered before an independent venture into the foreign field. It also provides some guidelines for conducting successful overseas operations. When properly assessed, foreign exploration is well within the reach of smaller U.S. independents and presents no greater risk than domestic exploration; the rewards, however, can be much larger. Furthermore, the Oil and Gas Journal surveys of the 300 largest U.S. petroleum companies show that companies with a consistent foreign exploration policy have fared better financially during difficult times

  2. Dissecting Bacterial Cell Wall Entry and Signaling in Eukaryotic Cells: an Actin-Dependent Pathway Parallels Platelet-Activating Factor Receptor-Mediated Endocytosis.

    Science.gov (United States)

    Loh, Lip Nam; Gao, Geli; Tuomanen, Elaine I

    2017-01-03

    The Gram-positive bacterial cell wall (CW) peptidoglycan-teichoic acid complex is released into the host environment during bacterial metabolism or death. It is a highly inflammatory Toll-like receptor 2 (TLR2) ligand, and previous in vivo studies have demonstrated its ability to recapitulate pathological features of pneumonia and meningitis. We report that an actin-dependent pathway is involved in the internalization of the CW by epithelial and endothelial cells, in addition to the previously described platelet-activating factor receptor (PAFr)-dependent uptake pathway. Unlike the PAFr-dependent pathway, which is mediated by clathrin and dynamin and does not lead to signaling, the alternative pathway is sensitive to 5-(N-ethyl-N-isopropyl) amiloride (EIPA) and engenders Rac1, Cdc42, and phosphatidylinositol 3-kinase (PI3K) signaling. Upon internalization by this macropinocytosis-like pathway, CW is trafficked to lysosomes. Intracellular CW trafficking is more complex than previously recognized and suggests multiple points of interaction with and without innate immune signaling. Streptococcus pneumoniae is a major human pathogen infecting the respiratory tract and brain. It is an established model organism for understanding how infection injures the host. During infection or bacterial growth, bacteria shed their cell wall (CW) into the host environment and trigger inflammation. A previous study has shown that CW enters and crosses cell barriers by interacting with a receptor on the surfaces of host cells, termed platelet-activating factor receptor (PAFr). In the present study, by using cells that are depleted of PAFr, we identified a second pathway with features of macropinocytosis, which is a receptor-independent fluid uptake mechanism by cells. Each pathway contributes approximately the same amount of cell wall trafficking, but the PAFr pathway is silent, while the new pathway appears to contribute to the host inflammatory response to CW insult. Copyright © 2017

  3. Independence in appearance

    DEFF Research Database (Denmark)

    Warming-Rasmussen, Bent; Quick, Reiner; Liempd, Dennis van

    2011-01-01

    In the wake of the financial crisis, the EU Commission has published a Green Paper on the future role of the audit function in Europe. The Green Paper lists a number of proposals for tighter rules for audits and auditors in order to contribute to stabilizing the financial system. The present...... article presents research contributions to the question whether the auditor is to continue to provide both audit and non-audit services (NAS) to an audit client. Research results show that this double function for the same audit client is a problem for stakeholders' confidence in auditor independence...

  4. The importance of board independence

    NARCIS (Netherlands)

    Zijl, N.J.M.

    2012-01-01

    Although the attributed importance of board independence is high, a clear definition of independence does not exist. Furthermore, the aim and consequences of independence are the subject of discussion and empirical evidence about the impact of independence is weak and disputable. Despite this lack

  5. Autonomy, Independence, Inclusion

    Directory of Open Access Journals (Sweden)

    Filippo Angelucci

    2015-04-01

    Full Text Available The living environment must not only meet the primary needs of living, but also the expectations of improvement of life and social relations and people’s work. The need for a living environment that responds to the needs of users with their different abilities, outside of standardizations, is increasingly felt as autonomy, independence and well-being are the result of real usability and adaptability of the spaces. The project to improve the inclusivity of living space and to promote the rehabilitation of fragile users need to be characterized as an interdisciplinary process in which the integration of specialized contributions leads to adaptive customization of space solutions and technological that evolve with the changing needs, functional capacities and abilities of individuals.

  6. Lessons from independence

    International Nuclear Information System (INIS)

    Hauptfuhrer, R.R.

    1990-01-01

    The recent history of Oryx provides invaluable lessons for those who plan future energy strategies, relates the author of this paper. When Oryx became an independent oil and gas company, its reserves were declining, its stock was selling below asset values, and the price of oil seemed stuck below $15 per barrel. The message from Oryx management to Oryx employees was: We are in charge of our own destiny. We are about to create our own future. Oryx had developed a new, positive corporate culture and the corporate credit required for growth. This paper points to two basic principles that have guided the metamorphosis in Oryx's performance. The first objective was to improve operational efficiency and to identify the right performance indicators to measure this improvement. It states that the most critical performance indicator for an exploration and production company must be replacement and expansion of reserves at a competitive replacement cost. Oryx has cut its finding costs from $12 to $5 per barrel, while the BP acquisition provided proven reserves at a cost of only $4 per barrel. Another performance indicator measures Oryx's standing in the financial markets

  7. Independents' group posts loss

    International Nuclear Information System (INIS)

    Sanders, V.; Price, R.B.

    1992-01-01

    Low oil gas prices and special charges caused the group of 50 U.S. independent producers Oil and Gas Journal tracks to post a combined loss in first half 1992. The group logged a net loss of $53 million in the first half compared with net earnings of $354 million in first half 1991, when higher oil prices during the Persian Gulf crisis buoyed earnings in spite of crude oil and natural gas production declines. The combined loss in the first half follows a 45% drop in the group's earnings in 1991 and compares with the OGJ group of integrated oil companies whose first half 1992 income fell 47% from the prior year. Special charges, generally related to asset writedowns, accounted for most of the almost $560 million in losses posted by about the third of the group. Nerco Oil and Gas Inc., Vancouver, Wash., alone accounted for almost half that total with charges related to an asset writedown of $238 million in the first quarter. Despite the poor first half performance, the outlook is bright for sharply improved group earnings in the second half, assuming reasonably healthy oil and gas prices and increased production resulting from acquisitions and in response to those prices

  8. PPARγ-Independent Mechanism

    Directory of Open Access Journals (Sweden)

    Christopher M. Hogan

    2011-01-01

    Full Text Available Acute and chronic lung inflammation is associated with numerous important disease pathologies including asthma, chronic obstructive pulmonary disease and silicosis. Lung fibroblasts are a novel and important target of anti-inflammatory therapy, as they orchestrate, respond to, and amplify inflammatory cascades and are the key cell in the pathogenesis of lung fibrosis. Peroxisome proliferator-activated receptor gamma (PPARγ ligands are small molecules that induce anti-inflammatory responses in a variety of tissues. Here, we report for the first time that PPARγ ligands have potent anti-inflammatory effects on human lung fibroblasts. 2-cyano-3, 12-dioxoolean-1, 9-dien-28-oic acid (CDDO and 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2 inhibit production of the inflammatory mediators interleukin-6 (IL-6, monocyte chemoattractant protein-1 (MCP-1, COX-2, and prostaglandin (PGE2 in primary human lung fibroblasts stimulated with either IL-1β or silica. The anti-inflammatory properties of these molecules are not blocked by the PPARγ antagonist GW9662 and thus are largely PPARγ independent. However, they are dependent on the presence of an electrophilic carbon. CDDO and 15d-PGJ2, but not rosiglitazone, inhibited NF-κB activity. These results demonstrate that CDDO and 15d-PGJ2 are potent attenuators of proinflammatory responses in lung fibroblasts and suggest that these molecules should be explored as the basis for novel, targeted anti-inflammatory therapies in the lung and other organs.

  9. Commonwealth of (Independent States

    Directory of Open Access Journals (Sweden)

    Vrućinić Dušan

    2013-01-01

    Full Text Available Following the stages from the establishment itself to the present day of the functioning of such a specific regional organization as the Commonwealth of Independent States (CIS, the article seeks to further explain the meaning of its existence, efficiency and functioning. The CIS was created in order to make the dissolution of a major world super-power, which throughout the 20th century together with the USA defined the bipolar world, as painless as possible, especially for the new countries and its nationally and ethnically diverse population. During the early years after the dissolution of the USSR, the CIS played a major role in a more flexible and less severe dissolution of the Soviet empire, alleviating the consequences for its people. A more efficient functioning among the republics in all fields was also one of the tasks of the Commonwealth, to which it was devoted to the extent which was permitted by the then, not too favourable circumstances. Difficult years of economic crisis did not allow the CIS to mutually integrate its members as much as possible on the economy level. Thanks to the economic recovery of the post-Soviet states in the early 21st century, the Commonwealth has also been transformed, reformed, and renewed, and all this in order to achieve better and more fruitful cooperation between the members. The CIS may serve as a proper example of how the former Soviet Union states are inextricably linked by social, security-political, economic, cultural, communication-transport, and other ties, thanks to the centuries-long existence of the peoples of these states in this area, despite both internal and external factors which occasionally, but temporarily halt the post-Soviet integration. Mathematically expressed, the CIS members are naturally predisposed, to be reciprocally depended on each other, just as they also have the capacity for successful cooperation in the future times and epochs brought on by the modern world.

  10. Media independence and dividend policy

    DEFF Research Database (Denmark)

    Farooq, Omar; Dandoune, Salma

    2012-01-01

    independence and dividend policies in emerging markets. Using a dataset from twenty three emerging markets, we show a significantly negative relationship between dividend policies (payout ratio and decision to pay dividend) and media independence. We argue that independent media reduces information asymmetries...... for stock market participants. Consequently, stock market participants in emerging markets with more independent media do not demand as high and as much dividends as their counterparts in emerging markets with less independent media. We also show that press independence is more important in defining......Can media pressurize managers to disgorge excess cash to shareholders? Do firms in countries with more independent media follow different dividend policies than firms with less independent media? This paper seeks to answer these questions and aims to document the relationship between media...

  11. Boards: Independent and Committed Directors?

    OpenAIRE

    Christophe Volonté

    2011-01-01

    Regulators, proxy advisors and shareholders are regularly calling for independent directors. However, at the same time, independent directors commonly engage in numerous outside activities potentially reducing their time and commitment with the particular firm. Using Tobin's Q as an approximation of market valuation and controlling for endogeneity, our empirical analysis reveals that neither is independence positively related to firm performance nor are outside activities negatively related t...

  12. Independent component analysis: recent advances

    OpenAIRE

    Hyv?rinen, Aapo

    2013-01-01

    Independent component analysis is a probabilistic method for learning a linear transform of a random vector. The goal is to find components that are maximally independent and non-Gaussian (non-normal). Its fundamental difference to classical multi-variate statistical methods is in the assumption of non-Gaussianity, which enables the identification of original, underlying components, in contrast to classical methods. The basic theory of independent component analysis was mainly developed in th...

  13. On independence in risk communication

    International Nuclear Information System (INIS)

    Lacronique, J. F.

    2006-01-01

    The term 'independence' is a common key word used by almost all stake holders in the field of nuclear safety regulation. The intention is to persuade the public that it can have more confidence and trust in the persons in charge, if their competence and judgment cannot be altered by any kind of political issue or personal interest. However, it is possible to discuss the reality of this claimed quality: how is it possible to verify that the organization that claim 'independence' really respect it? National expertise Institutions can show that they are independent from the industry, but can they claim total independence from the government? NGO have build a large part of their constituency on 'independence' from industry and governments, but are they independent from the ideological forces -sometimes very powerful - that support them? How can we achieve to make this noble word really meaningful? We will show through different examples, that 'independence' is by definition a fragile and versatile challenge, rather than a durable label. It has to be refreshed regularly and thoroughly. Risk communication, in that context, must respect principles which will build independence as a solid asset, and keep a certain distance with mere marketing purposes or candid wishful thinking

  14. Defining and Selecting Independent Directors

    Directory of Open Access Journals (Sweden)

    Eric Pichet

    2017-10-01

    Full Text Available Drawing from the Enlightened Shareholder Theory that the author first developed in 2011, this theoretical paper with practical and normative ambitions achieves a better definition of independent director, while improving the understanding of the roles he fulfils on boards of directors. The first part defines constructs like firms, Governance system and Corporate governance, offering a clear distinction between the latter two concepts before explaining the four main missions of a board. The second part defines the ideal independent director by outlining the objective qualities that are necessary and adding those subjective aspects that have turned this into a veritable profession. The third part defines the ideal process for selecting independent directors, based on nominating committees that should themselves be independent. It also includes ways of assessing directors who are currently in function, as well as modalities for renewing their mandates. The paper’s conclusion presents the Paradox of the Independent Director.

  15. Logical independence and quantum randomness

    International Nuclear Information System (INIS)

    Paterek, T; Kofler, J; Aspelmeyer, M; Zeilinger, A; Brukner, C; Prevedel, R; Klimek, P

    2010-01-01

    We propose a link between logical independence and quantum physics. We demonstrate that quantum systems in the eigenstates of Pauli group operators are capable of encoding mathematical axioms and show that Pauli group quantum measurements are capable of revealing whether or not a given proposition is logically dependent on the axiomatic system. Whenever a mathematical proposition is logically independent of the axioms encoded in the measured state, the measurement associated with the proposition gives random outcomes. This allows for an experimental test of logical independence. Conversely, it also allows for an explanation of the probabilities of random outcomes observed in Pauli group measurements from logical independence without invoking quantum theory. The axiomatic systems we study can be completed and are therefore not subject to Goedel's incompleteness theorem.

  16. Logical independence and quantum randomness

    Energy Technology Data Exchange (ETDEWEB)

    Paterek, T; Kofler, J; Aspelmeyer, M; Zeilinger, A; Brukner, C [Institute for Quantum Optics and Quantum Information, Austrian Academy of Sciences, Boltzmanngasse 3, A-1090 Vienna (Austria); Prevedel, R; Klimek, P [Faculty of Physics, University of Vienna, Boltzmanngasse 5, A-1090 Vienna (Austria)], E-mail: tomasz.paterek@univie.ac.at

    2010-01-15

    We propose a link between logical independence and quantum physics. We demonstrate that quantum systems in the eigenstates of Pauli group operators are capable of encoding mathematical axioms and show that Pauli group quantum measurements are capable of revealing whether or not a given proposition is logically dependent on the axiomatic system. Whenever a mathematical proposition is logically independent of the axioms encoded in the measured state, the measurement associated with the proposition gives random outcomes. This allows for an experimental test of logical independence. Conversely, it also allows for an explanation of the probabilities of random outcomes observed in Pauli group measurements from logical independence without invoking quantum theory. The axiomatic systems we study can be completed and are therefore not subject to Goedel's incompleteness theorem.

  17. Algae: America's Pathway to Independence

    National Research Council Canada - National Science Library

    Custer, James

    2007-01-01

    .... Oil dependency is an unacceptable risk to U.S. national strategy. This paper advocates independence from foreign oil by converting the national transportation fleet to biodiesel derived from algae...

  18. Independent production and Poisson distribution

    International Nuclear Information System (INIS)

    Golokhvastov, A.I.

    1994-01-01

    The well-known statement of factorization of inclusive cross-sections in case of independent production of particles (or clusters, jets etc.) and the conclusion of Poisson distribution over their multiplicity arising from it do not follow from the probability theory in any way. Using accurately the theorem of the product of independent probabilities, quite different equations are obtained and no consequences relative to multiplicity distributions are obtained. 11 refs

  19. Endocytosis of desmosomal plaques depends on intact actin filaments and leads to a nondegradative compartment

    DEFF Research Database (Denmark)

    Holm, Pernille K.; Hansen, Steen H.; Sandvig, Kirsten

    1993-01-01

    Cellebiologi, human epithelial cell line, growth inhibition, desmosomes, clathrin-independent endocytosis, cytoskeleton, nondegradative compartment......Cellebiologi, human epithelial cell line, growth inhibition, desmosomes, clathrin-independent endocytosis, cytoskeleton, nondegradative compartment...

  20. Food Independence of the Region

    Directory of Open Access Journals (Sweden)

    Vasiliy Vladimirovich Tyutyunik

    2016-06-01

    Full Text Available The article deals with such basic definitions as food security, food independence and food self- sufficiency of the region. The author shows the ambiguity problem of interpretations of these terms in the Russian legislation, which is especially evident in the transition from the national to the regional level. Using the example of legislative acts of some of the Russian Federation’s subjects the study demonstrates the incorrect use of mentioned terms. In author’s opinion, regional authorities in the Russian Federation must introduce amendments to the legislative documents concerning food security. To be more concrete, the regional authorities should either deny the goal of food independence for a particular region, or specify that the goal of reaching food independence for the region does not mean food self-sufficiency, but just import substitution on the regional level

  1. Supplying safety and energy independence

    International Nuclear Information System (INIS)

    Maillard, D.

    2001-03-01

    The french Observatory of the Energy wonders about the energy independence notion. Many risks are possible: physical, economical, geo-political, social and ecological risks. Because those risks are numerous, the answers for a supplying safety are also numerous. In this context the energy policy is a difficult art which the public opinion needs to be more and more aware. (A.L.B.)

  2. Independent Study Project, Topic: Topology.

    Science.gov (United States)

    Notre Dame High School, Easton, PA.

    Using this guide and the four popular books noted in it, a student, working independently, will learn about some of the classical ideas and problems of topology: the Meobius strip and Klein bottle, the four color problem, genus of a surface, networks, Euler's formula, and the Jordan Curve Theorem. The unit culminates in a project of the students'…

  3. Charge independence and charge symmetry

    Energy Technology Data Exchange (ETDEWEB)

    Miller, G A [Washington Univ., Seattle, WA (United States). Dept. of Physics; van Oers, W T.H. [Manitoba Univ., Winnipeg, MB (Canada). Dept. of Physics; [TRIUMF, Vancouver, BC (Canada)

    1994-09-01

    Charge independence and charge symmetry are approximate symmetries of nature, violated by the perturbing effects of the mass difference between up and down quarks and by electromagnetic interactions. The observations of the symmetry breaking effects in nuclear and particle physics and the implications of those effects are reviewed. (author). 145 refs., 3 tabs., 11 figs.

  4. Charge independence and charge symmetry

    International Nuclear Information System (INIS)

    Miller, G.A.

    1994-09-01

    Charge independence and charge symmetry are approximate symmetries of nature, violated by the perturbing effects of the mass difference between up and down quarks and by electromagnetic interactions. The observations of the symmetry breaking effects in nuclear and particle physics and the implications of those effects are reviewed. (author). 145 refs., 3 tabs., 11 figs

  5. The Regulatory Independence of FANR

    International Nuclear Information System (INIS)

    ALNuaimi, Fatema; Choi, Kwang Shik

    2012-01-01

    Regulatory independence is meant to provide a conservative system of policy making in order to comply with the problems that are forecasted upon the basis of assumptions. The Federal Authorization of Nuclear Regulation (FANR) is a regulatory commission that was formed to be regulatory body that governs the generation of nuclear power in United Arab Emirates. It was established under the UAE nuclear law (9/2009) as an independent regulatory body that was tasked with the regulation of all nuclear activities in the United Arab Emirates. As an independent body, FANR was tasked with ensuring that the regulation of the nuclear sector is done in effective and transparent manner to ensure its accountability to the people. Being independent, the regulatory body develops national nuclear regulations based on laid down safety standards by the International Atomic Energy Agency, ensuring that they are based on scientific and proven technologies The role of FANR is to ensure that the all corporations that undertake nuclear activities follow the laid down procedures and objectives and ensure safety measures are taken keenly to ensure the safety of the workers and the general public while at the same time ensuring the environment is free from nuclear radiations

  6. Characteristics of Independent Music Teachers

    Science.gov (United States)

    Upitis, Rena; Abrami, Philip C.; Brook, Julia; Boese, Karen; King, Matthew

    2017-01-01

    The purpose of the present study was to learn about the characteristics of independent music teachers, their beliefs about music teaching, and their studio practices. A self-report survey included questions about the teachers' (a) background experiences, (b) pedagogical approaches, (c) use of digital technologies, and (d) professional development…

  7. The Regulatory Independence of FANR

    Energy Technology Data Exchange (ETDEWEB)

    ALNuaimi, Fatema; Choi, Kwang Shik [Korea Advanced Institute of Science and Technology, Daejeon (Korea, Republic of)

    2012-05-15

    Regulatory independence is meant to provide a conservative system of policy making in order to comply with the problems that are forecasted upon the basis of assumptions. The Federal Authorization of Nuclear Regulation (FANR) is a regulatory commission that was formed to be regulatory body that governs the generation of nuclear power in United Arab Emirates. It was established under the UAE nuclear law (9/2009) as an independent regulatory body that was tasked with the regulation of all nuclear activities in the United Arab Emirates. As an independent body, FANR was tasked with ensuring that the regulation of the nuclear sector is done in effective and transparent manner to ensure its accountability to the people. Being independent, the regulatory body develops national nuclear regulations based on laid down safety standards by the International Atomic Energy Agency, ensuring that they are based on scientific and proven technologies The role of FANR is to ensure that the all corporations that undertake nuclear activities follow the laid down procedures and objectives and ensure safety measures are taken keenly to ensure the safety of the workers and the general public while at the same time ensuring the environment is free from nuclear radiations

  8. Field development finance for independents

    International Nuclear Information System (INIS)

    Whyatt, A.S.

    1995-01-01

    Worldwide, oil and gas reserves are in decline, and independents own relatively little of them, say 13 percent of the oil reserves and 22 percent of the gas reserves. Over the five years 1989-93, the oil reserves of majors declined by 4.5 percent, while those of independents rose 17 percent; each experienced a rise in gas reserves of 6-7 percent. Partly because of this gentle decline in world reserves, but much more because of the decline in oil and gas commodity prices, the value of the reserves, expressed in terms of future production, has been declining substantially. In 1993, when these data were last recorded, the discounted future net cash flows in the United States were 40 percent below their 1990 peak of $135 billion, and foreign net cash flows were 35 percent lower than the 1990 peak of $140 billion. (author)

  9. A definition of background independence

    International Nuclear Information System (INIS)

    Gryb, Sean

    2010-01-01

    We propose a definition for background (in)/dependence in dynamical theories of the evolution of configurations that have a continuous symmetry and test this definition on particle models and on gravity. Our definition draws from Barbour's best matching framework developed for the purpose of implementing spatial and temporal relationalism. Among other interesting theories, general relativity can be derived within this framework in novel ways. We study the detailed canonical structure of a wide range of best matching theories and show that their actions must have a local gauge symmetry. When gauge theory is derived in this way, we obtain at the same time a conceptual framework for distinguishing between background-dependent and -independent theories. Gauge invariant observables satisfying Kuchar's criterion are identified and, in simple cases, explicitly computed. We propose a procedure for inserting a global background time into temporally relational theories. Interestingly, using this procedure in general relativity leads to unimodular gravity.

  10. [Accreditation of Independent Ethics Committees].

    Science.gov (United States)

    Ramiro Avilés, Miguel A

    According to Law 14/2007 and Royal Decree 1090/2015, biomedical research must be assessed by an Research Ethics Committee (REC), which must be accredited as an Research ethics committee for clinical trials involving medicinal products (RECm) if the opinion is issued for a clinical trial involving medicinal products or clinical research with medical devices. The aim of this study is to ascertain how IEC and IECm accreditation is regulated. National and regional legislation governing biomedical research was analysed. No clearly-defined IEC or IECm accreditation procedures exist in the national or regional legislation. Independent Ethics Committees are vital for the development of basic or clinical biomedical research, and they must be accredited by an external body in order to safeguard their independence, multidisciplinary composition and review procedures. Copyright © 2016 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.

  11. RIPE [robot independent programming environment]: A robot independent programming environment

    International Nuclear Information System (INIS)

    Miller, D.J.; Lennox, R.C.

    1990-01-01

    Remote manual operations in radiation environments are typically performed very slowly. Sensor-based computer-controlled robots hold great promise for increasing the speed and safety of remote operations; however, the programming of robotic systems has proven to be expensive and difficult. Generalized approaches to robot programming that reuse available software modules and employ programming languages which are independent of the specific robotic and sensory devices being used are needed to speed software development and increase overall system reliability. This paper discusses the robot independent programming environment (RIPE) developed at Sandia National Laboratories (SNL). The RIPE is an object-oriented approach to robot system architectures; it is a software environment that facilitates rapid design and implementation of complex robot systems for diverse applications. An architecture based on hierarchies of distributed multiprocessors provides the computing platform for a layered programming structure that models applications using software objects. These objects are designed to support model-based automated programming of robotic and machining devices, real-time sensor-based control, error handling, and robust communication

  12. Independent EEG sources are dipolar.

    Directory of Open Access Journals (Sweden)

    Arnaud Delorme

    Full Text Available Independent component analysis (ICA and blind source separation (BSS methods are increasingly used to separate individual brain and non-brain source signals mixed by volume conduction in electroencephalographic (EEG and other electrophysiological recordings. We compared results of decomposing thirteen 71-channel human scalp EEG datasets by 22 ICA and BSS algorithms, assessing the pairwise mutual information (PMI in scalp channel pairs, the remaining PMI in component pairs, the overall mutual information reduction (MIR effected by each decomposition, and decomposition 'dipolarity' defined as the number of component scalp maps matching the projection of a single equivalent dipole with less than a given residual variance. The least well-performing algorithm was principal component analysis (PCA; best performing were AMICA and other likelihood/mutual information based ICA methods. Though these and other commonly-used decomposition methods returned many similar components, across 18 ICA/BSS algorithms mean dipolarity varied linearly with both MIR and with PMI remaining between the resulting component time courses, a result compatible with an interpretation of many maximally independent EEG components as being volume-conducted projections of partially-synchronous local cortical field activity within single compact cortical domains. To encourage further method comparisons, the data and software used to prepare the results have been made available (http://sccn.ucsd.edu/wiki/BSSComparison.

  13. On Judicial and Quasi-Judicial Independence

    NARCIS (Netherlands)

    Comtois, Suzanne; de Graaf, K.J.

    2013-01-01

    'Principles of judicial and quasi-judicial independence are fundamental to all democracies and yet, the notion of independence is still elusive. What is judicial and quasi-judicial independence and why is it important? From whom and what are the judiciary and other adjudicators to be independent? Is

  14. Worker flag. Independent Electrical Policy

    International Nuclear Information System (INIS)

    Bahen, D.

    2000-01-01

    This work analyses the initiative of privatization of the Mexican Electric Industry and also it is showed the incoherence of this mistaken proposal. Along the same line is analysed tthe situation of the National Electric Sector and the working process for the distinct types of electric generation just as the syndical and labor situations. In consequence it is proposed an Independent Electrical Policy, which includes the integration of the Nationalized Electric Industry, the syndical union and the Unique Collective Contract. The purpose of this work is to contribute to the success of the electrical and nuclear struggle always maintaining in rising position the red flag of the proletariat. The author considers that the privatization means mercantilization of the human necessities. The privatization is not inevitable at condition of to exercise consequently the political actions necessary through alternatives includes: the worker control of production, research, and the National Electric strike. (Author)

  15. Ergodic theory independence and dichotomies

    CERN Document Server

    Kerr, David

    2016-01-01

    This book provides an introduction to the ergodic theory and topological dynamics of actions of countable groups. It is organized around the theme of probabilistic and combinatorial independence, and highlights the complementary roles of the asymptotic and the perturbative in its comprehensive treatment of the core concepts of weak mixing, compactness, entropy, and amenability. The more advanced material includes Popa's cocycle superrigidity, the Furstenberg-Zimmer structure theorem, and sofic entropy. The structure of the book is designed to be flexible enough to serve a variety of readers. The discussion of dynamics is developed from scratch assuming some rudimentary functional analysis, measure theory, and topology, and parts of the text can be used as an introductory course. Researchers in ergodic theory and related areas will also find the book valuable as a reference.

  16. Chandra Independently Determines Hubble Constant

    Science.gov (United States)

    2006-08-01

    A critically important number that specifies the expansion rate of the Universe, the so-called Hubble constant, has been independently determined using NASA's Chandra X-ray Observatory. This new value matches recent measurements using other methods and extends their validity to greater distances, thus allowing astronomers to probe earlier epochs in the evolution of the Universe. "The reason this result is so significant is that we need the Hubble constant to tell us the size of the Universe, its age, and how much matter it contains," said Max Bonamente from the University of Alabama in Huntsville and NASA's Marshall Space Flight Center (MSFC) in Huntsville, Ala., lead author on the paper describing the results. "Astronomers absolutely need to trust this number because we use it for countless calculations." Illustration of Sunyaev-Zeldovich Effect Illustration of Sunyaev-Zeldovich Effect The Hubble constant is calculated by measuring the speed at which objects are moving away from us and dividing by their distance. Most of the previous attempts to determine the Hubble constant have involved using a multi-step, or distance ladder, approach in which the distance to nearby galaxies is used as the basis for determining greater distances. The most common approach has been to use a well-studied type of pulsating star known as a Cepheid variable, in conjunction with more distant supernovae to trace distances across the Universe. Scientists using this method and observations from the Hubble Space Telescope were able to measure the Hubble constant to within 10%. However, only independent checks would give them the confidence they desired, considering that much of our understanding of the Universe hangs in the balance. Chandra X-ray Image of MACS J1149.5+223 Chandra X-ray Image of MACS J1149.5+223 By combining X-ray data from Chandra with radio observations of galaxy clusters, the team determined the distances to 38 galaxy clusters ranging from 1.4 billion to 9.3 billion

  17. Testing Local Independence between Two Point Processes

    DEFF Research Database (Denmark)

    Allard, Denis; Brix, Anders; Chadæuf, Joël

    2001-01-01

    Independence test, Inhomogeneous point processes, Local test, Monte Carlo, Nonstationary, Rotations, Spatial pattern, Tiger bush......Independence test, Inhomogeneous point processes, Local test, Monte Carlo, Nonstationary, Rotations, Spatial pattern, Tiger bush...

  18. The Independent Payment Advisory Board.

    Science.gov (United States)

    Manchikanti, Laxmaiah; Falco, Frank J E; Singh, Vijay; Benyamin, Ramsin M; Hirsch, Joshua A

    2011-01-01

    The Independent Payment Advisory Board (IPAB) is a vastly powerful component of the president's health care reform law, with authority to issue recommendations to reduce the growth in Medicare spending, providing recommendations to be considered by Congress and implemented by the administration on a fast track basis. Ever since its inception, IPAB has been one of the most controversial issues of the Patient Protection and Affordable Care Act (ACA), even though the powers of IPAB are restricted and multiple sectors of health care have been protected in the law. IPAB works by recommending policies to Congress to help Medicare provide better care at a lower cost, which would include ideas on coordinating care, getting rid of waste in the system, providing incentives for best practices, and prioritizing primary care. Congress then has the power to accept or reject these recommendations. However, Congress faces extreme limitations, either to enact policies that achieve equivalent savings, or let the Secretary of Health and Human Services (HHS) follow IPAB's recommendations. IPAB has strong supporters and opponents, leading to arguments in favor of or against to the extreme of introducing legislation to repeal IPAB. The origins of IPAB are found in the ideology of the National Institute for Health and Clinical Excellence (NICE) and the impetus of exploring health care costs, even though IPAB's authority seems to be limited to Medicare only. The structure and operation of IPAB differs from Medicare and has been called the Medicare Payment Advisory Commission (MedPAC) on steroids. The board membership consists of 15 full-time members appointed by the president and confirmed by the Senate with options for recess appointments. The IPAB statute sets target growth rates for Medicare spending. The applicable percent for maximum savings appears to be 0.5% for year 2015, 1% for 2016, 1.25% for 2017, and 1.5% for 2018 and later. The IPAB Medicare proposal process involves

  19. Does firm performance affect board independence?

    Directory of Open Access Journals (Sweden)

    Yi Wang

    2010-07-01

    Full Text Available This paper seeks to shed some light on the antecedents of board independence. Specifically, it attempts to test the conceptual frameworks which make different predictions about the effect of firm performance on the level of board independence. The results provide support for the perspective that appointing more independent members to the boards may merely represent firms’ attempts to comply with institutional pressures. It is found that higher blockholder shareholdings lead to lower independence on the board, and audit and remuneration committees. Moreover, larger firms have relatively more independent directors sitting on nomination and remuneration committees.

  20. Autonomy and independence in language learning

    CERN Document Server

    Benson, Phil

    2014-01-01

    The topics of autonomy and independence play an increasingly important role in language education. They raise issues such as learners' responsibility for their own learning, and their right to determine the direction of their own learning, the skills which can be learned and applied in self-directed learning and capacity for independent learning and the extents to which this can be suppressed by institutional education. This volume offers new insights into the principles of autonomy and independence and the practices associated with them focusing on the area of EFL teaching. The editors' introduction provides the context and outlines the main issues involved in autonomy and independence. Later chapters discuss the social and political implications of autonomy and independence and their effects on educational structures. The consequences for the design of learner-centred materials and methods is discussed, together with an exploration of the practical ways of implementing autonomy and independence in language ...

  1. Calibration and Propagation of Uncertainty for Independence

    Energy Technology Data Exchange (ETDEWEB)

    Holland, Troy Michael [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Kress, Joel David [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Bhat, Kabekode Ghanasham [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2017-06-30

    This document reports on progress and methods for the calibration and uncertainty quantification of the Independence model developed at UT Austin. The Independence model is an advanced thermodynamic and process model framework for piperazine solutions as a high-performance CO2 capture solvent. Progress is presented in the framework of the CCSI standard basic data model inference framework. Recent work has largely focused on the thermodynamic submodels of Independence.

  2. Advanced practice nurses: starting an independent practice.

    Science.gov (United States)

    Lambert, V A; Lambert, C E

    1996-01-01

    Independent or private practice is the delivery of nursing services provided by nurses over which nurses have full control. With a changing healthcare system, nurses are in a prime position to negotiate the delivery of appropriate, acceptable, and cost-effective health care as independent practitioners. This article addresses the mission and goals of independent practice, community need, business structure of the practice, housing the practice, legal considerations, financing the practice, marketing issues, clientele, record keeping, and reimbursement.

  3. 12 CFR 564.5 - Appraiser independence.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 5 2010-01-01 2010-01-01 false Appraiser independence. 564.5 Section 564.5 Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY APPRAISALS § 564.5 Appraiser independence. (a) Staff appraisers. If an appraisal is prepared by a staff appraiser, that appraiser must be...

  4. Becoming independent through au pair migration

    DEFF Research Database (Denmark)

    Dalgas, Karina Märcher

    2015-01-01

    . This article argues that, despite this critique, au pairing does play an important formative role for young Filipinas because it opens up for experiences abroad that enable them to be recognised as independent adults in Philippine society. Rather than autonomy, however, au pairs define their independence...

  5. Uniqueness of time-independent electromagnetic fields

    DEFF Research Database (Denmark)

    Karlsson, Per W.

    1974-01-01

    As a comment on a recent paper by Steele, a more general uniqueness theorem for time-independent fields is mentioned. ©1974 American Institute of Physics......As a comment on a recent paper by Steele, a more general uniqueness theorem for time-independent fields is mentioned. ©1974 American Institute of Physics...

  6. Outer-2-independent domination in graphs

    Indian Academy of Sciences (India)

    independent dominating set of a graph is a set of vertices of such that every vertex of ()\\ has a neighbor in and the maximum vertex degree of the subgraph induced by ()\\ is at most one. The outer-2-independent domination ...

  7. An architecture for device independent interfacing

    International Nuclear Information System (INIS)

    Pace, D.M.

    1990-01-01

    Achieving device independence for software applications is required for all but a small number of critical real time applications. Device independence is achieved by establishing protocols and building protocol interpreters for the specific devices. Data structures containing pointers to functions provide a flexible architecture for implementing protocol translation. 3 refs., 5 figs

  8. Institutional independence and the constitutionality of legislation ...

    African Journals Online (AJOL)

    The test for determining whether judicial independence is safeguarded is an objective one based on public confidence in the structure of the court and the ... in the analysis of the application of the principles of judicial independence to specific legislative schemes where the structure of the tribunal thereby established had ...

  9. 48 CFR 3.103 - Independent pricing.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Independent pricing. 3.103 Section 3.103 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION GENERAL IMPROPER BUSINESS PRACTICES AND PERSONAL CONFLICTS OF INTEREST Safeguards 3.103 Independent pricing. ...

  10. Accounting for Independent Schools. Second Edition.

    Science.gov (United States)

    National Association of Independent Schools, Boston, MA.

    This is a thoroughly revised edition of the 1969 publication, "Accounting for Independent Schools," a guide that attempted to codify basic accounting principles and practices for specific application to independent schools. The focus of the second edition is more on refining practices than on initiating them, and more on extending the managerial…

  11. Central bank independence and financial instability

    NARCIS (Netherlands)

    Klomp, J.G.; de Haan, J.

    2009-01-01

    It has been argued that central bank independence (CBI) may not only be beneficial for reaching the objective of price stability, but also for maintaining financial stability. Greater independence from external pressure implies that central banks are less politically constrained in acting to prevent

  12. 47 CFR 64.904 - Independent audits.

    Science.gov (United States)

    2010-10-01

    ... independent auditor every two years, covering the prior two year period, or have a financial audit performed by an independent auditor every two years, covering the prior two year period. In either case, the... of the auditor's report. At least 30 days prior to beginning the attestation engagement, the...

  13. Reflections on independence in nurse practitioner practice.

    Science.gov (United States)

    Weiland, Sandra A

    2008-07-01

    To examine factors that influence the ability of nurse practitioners (NPs) to practice as independent primary care providers. Extensive literature search on CINAHL, OVID, MEDLINE, Internet journal sources, and professional association Web sites. The legal authority for NPs to practice independently is recognized; however, the ability to put that authority into practice is undermined by the historical failure of political, professional, and social entities to recognize NPs as providers capable of providing primary care autonomously. Nonrecognition is responsible for complex reimbursement policies (both federal and state) that economically and professionally restrain the NP role; hence, NPs remain in a financially dependent relationship despite 40 years of proven safe practice. NPs must articulate their independence as practitioners more vociferously in order to meet society's healthcare requirements, as well as to attain professional fulfillment and forge collegial relationships. NPs will never be seen as members of a profession by either themselves or others without the practicality of independence and autonomy. Although legal independence is a fact, real practice independence in the pragmatic sense is contingent upon reimbursement. Without fiscal sustainability, practice independence is an impossibility. And, without professional autonomy, NPs will have only an employee's voice in the dynamic healthcare system in which they are really key players in providing healthcare services to the poor and undeserved populations.

  14. Independence, Odd Girth, and Average Degree

    DEFF Research Database (Denmark)

    Löwenstein, Christian; Pedersen, Anders Sune; Rautenbach, Dieter

    2011-01-01

      We prove several tight lower bounds in terms of the order and the average degree for the independence number of graphs that are connected and/or satisfy some odd girth condition. Our main result is the extension of a lower bound for the independence number of triangle-free graphs of maximum...... degree at most three due to Heckman and Thomas [Discrete Math 233 (2001), 233–237] to arbitrary triangle-free graphs. For connected triangle-free graphs of order n and size m, our result implies the existence of an independent set of order at least (4n−m−1) / 7.  ...

  15. On Independence for Capacities with Law of Large Numbers

    OpenAIRE

    Huang, Weihuan

    2017-01-01

    This paper introduces new notions of Fubini independence and Exponential independence of random variables under capacities to fit Ellsberg's model, and finds out the relationships between Fubini independence, Exponential independence, MacCheroni and Marinacci's independence and Peng's independence. As an application, we give a weak law of large numbers for capacities under Exponential independence.

  16. Massively Parallel Dimension Independent Adaptive Metropolis

    KAUST Repository

    Chen, Yuxin

    2015-01-01

    parameter dimension, by respecting the variance, for Gaussian targets. The result- ing algorithm, referred to as the dimension-independent adaptive Metropolis (DIAM) algorithm, also shows improved performance with respect to adaptive Metropolis on non

  17. Materialism, status consumption, and consumer independence.

    Science.gov (United States)

    Goldsmith, Ronald Earl; Clark, Ronald A

    2012-01-01

    Materialism influences many people. We focus on two aspects of this influence: reactions to prestige products and to the influence of others. A study of 187 U.S. student consumers shows that materialism is positively related to buying products that confer status. In contrast, materialism is negatively related to consumer independence, an enduring tendency to pay minimal attention to the prescribed norms of other consumers and to make product and brand decisions according to personal preferences. Consuming products for status is also negatively related to consumer independence. Moreover, the association between materialism and consumer independence is completely mediated by consuming for status. Materialism urges consumers to be status conscious so that they follow social norms in purchasing, but seeking status through goods is avoided by less materialistic, independent consumers. A second study (n = 258) also using student consumers confirmed these results.

  18. Quantum background independence in string theory

    International Nuclear Information System (INIS)

    Witten, E.

    1994-01-01

    Not only in physical string theories, but also in some highly simplified situations, background independence has been difficult to understand. It is argued that the ''holomorphic anomaly'' of Bershadsky, Cecotti, Ooguri and Vafa gives a fundamental explanation of some of the problems. Moreover, their anomaly equation can be interpreted in terms of a rather peculiar quantum version of background independence: in systems afflicted by the anomaly, background independence does not hold order by order in perturbation theory, but the exact partition function as a function of the coupling constants has a background independent interpretation as a state in an auxiliary quantum Hilbert space. The significance of this auxiliary space is otherwise unknown. (author). 23 refs

  19. Monitoring Progress toward Independent Silent Reading.

    Science.gov (United States)

    Franc, Lillian H.; Hildebrandt, Jeannette

    1984-01-01

    Concludes, among other things, that fluent oral reading is an important step toward reading for meaning and independent silent reading and that silent reading should be encouraged from the beginning of reading instruction. (FL)

  20. Update on the independent radiation monitor (IRM)

    International Nuclear Information System (INIS)

    Kroening, P.M.; Mucha, R.

    1976-01-01

    The new independent radiation monitor (IRM), unlike its predecessor, is a reliable and sensitive safety device for any radiation therapy room. It shows unequivocally that the beam is on, and it is inexpensive and simple to construct

  1. Quantum cryptography: The power of independence

    Science.gov (United States)

    Ekert, Artur

    2018-02-01

    Device-independent quantum cryptography promises unprecedented security, but it is regarded as a theorist's dream and an experimentalist's nightmare. A new mathematical tool has now pushed its experimental demonstration much closer to reality.

  2. What is Happening with Independent System Operators?

    Energy Technology Data Exchange (ETDEWEB)

    Porter, K. L.

    1999-02-01

    Emerging independent system operators (ISOs) appear to have many advantages for the wind power industry. This paper compares some past research on wind and transmission issues with some of the developments in ISO design and implementation.

  3. Kernel-based tests for joint independence

    DEFF Research Database (Denmark)

    Pfister, Niklas; Bühlmann, Peter; Schölkopf, Bernhard

    2018-01-01

    if the $d$ variables are jointly independent, as long as the kernel is characteristic. Based on an empirical estimate of dHSIC, we define three different non-parametric hypothesis tests: a permutation test, a bootstrap test and a test based on a Gamma approximation. We prove that the permutation test......We investigate the problem of testing whether $d$ random variables, which may or may not be continuous, are jointly (or mutually) independent. Our method builds on ideas of the two variable Hilbert-Schmidt independence criterion (HSIC) but allows for an arbitrary number of variables. We embed...... the $d$-dimensional joint distribution and the product of the marginals into a reproducing kernel Hilbert space and define the $d$-variable Hilbert-Schmidt independence criterion (dHSIC) as the squared distance between the embeddings. In the population case, the value of dHSIC is zero if and only...

  4. Opening A New Independent Pharmacy 101

    Directory of Open Access Journals (Sweden)

    Azam Elabed

    2016-02-01

    Full Text Available Opening an independent pharmacy is a process that involves multiple components. The rationale of this project is to discuss different issues that must be investigated prior to opening a new independency pharmacy. This includes the location, structure of the corporation, start-up cost, picking a wholesaler, fulfilling state board requirements and Philadelphia requirements, having a valid license, making professional relationships, and knowing basic marketing research. Methods used include using the knowledge and expertise from an independent pharmacy owner, visiting pharmacies, and interviewing neighbors for basic marketing research. Many aspects of opening an independent pharmacy differ significantly from a retail pharmacy, as there are various issues within the pharmacy and outside the pharmacy that must be extensively researched prior to opening in order to be successful.   Type: Student Project

  5. NMFS Fishery-Independent Survey System (FINSS)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Fishery Independent Survey System (FINSS) is a national system that characterizes NMFS ocean observation activities, stock and ecosystem data collections during...

  6. Qualification of organizations for independent technical supervision

    International Nuclear Information System (INIS)

    1981-04-01

    The requirements are established on trial for the qualification of an organization as an independent technical supervision organization in nuclear facilities, in activities related with quality assurance programs. (I.C.R.) [pt

  7. Alternative Perspectives on Independence of Directors

    OpenAIRE

    Brennan, Niamh; McDermott, Michael

    2004-01-01

    This paper examines the issue of independence of boards of directors and non-executive directors of companies listed on the Irish Stock Exchange. Based on information published in annual reports, the study found that most Irish listed companies were complying with the Combined Code’s recommendations for a balanced board structure, albeit with only 60 per cent having majority-independent boards. The study found a lack of consistency in interpreting the definition of “independence”, a lack of d...

  8. Salicylic acid-independent plant defence pathways

    OpenAIRE

    Pieterse, C.M.J.; Loon, L.C. van

    1999-01-01

    Salicylic acid is an important signalling molecule involved in both locally and systemically induced disease resistance responses. Recent advances in our understanding of plant defence signalling have revealed that plants employ a network of signal transduction pathways, some of which are independent of salicylic acid. Evidence is emerging that jasmonic acid and ethylene play key roles in these salicylic acid-independent pathways. Cross-talk between the salicylic acid-dependent and the salicy...

  9. Path dependence and independent utility regulation

    DEFF Research Database (Denmark)

    Ibsen, Christian Lyhne; Skovgaard Poulsen, Lauge

    2007-01-01

    The establishment of the Danish independent regulatory authorities for the energy and telecommunications sectors was based upon EU directives as part of their liberalisation process. Following the concepts of transaction costs and path dependency this article analyses differences in independence...... between the two authorities - the Danish Energy Regulatory Authority (Energitilsynet) and the National IT and Telecommunications Agency (IT- og Telestyrelsen) respectively. We find that the state's negligible interest in the energy sector until the 1970s formed the basis for strong energy companies...

  10. Efficient algorithms for conditional independence inference

    Czech Academy of Sciences Publication Activity Database

    Bouckaert, R.; Hemmecke, R.; Lindner, S.; Studený, Milan

    2010-01-01

    Roč. 11, č. 1 (2010), s. 3453-3479 ISSN 1532-4435 R&D Projects: GA ČR GA201/08/0539; GA MŠk 1M0572 Institutional research plan: CEZ:AV0Z10750506 Keywords : conditional independence inference * linear programming approach Subject RIV: BA - General Mathematics Impact factor: 2.949, year: 2010 http://library.utia.cas.cz/separaty/2010/MTR/studeny-efficient algorithms for conditional independence inference.pdf

  11. A generalized notion of semantic independence

    DEFF Research Database (Denmark)

    Fränzle, Martin; Stengel, Bernhard von; Wittmüss, Arne

    1995-01-01

    For programs represented semantically as relations, a concept of semantic independence is defined that is more general than previously stated notions. It allows for shared input variables and irrelevant interference due to nondeterminism.......For programs represented semantically as relations, a concept of semantic independence is defined that is more general than previously stated notions. It allows for shared input variables and irrelevant interference due to nondeterminism....

  12. On the k-independence required by linear probing and minwise independence

    DEFF Research Database (Denmark)

    Pǎtraşcu, Mihai; Thorup, Mikkel

    2016-01-01

    We show that linear probing requires 5-independent hash functions for expected constant-time performance, matching an upper bound of Pagh et al. [2009]. More precisely, we construct a random 4-independent hash function yielding expected logarithmic search time for certain keys. For (1 + ε......)-approximate minwise independence, we show that Ω(lg1 ε)-independent hash functions are required, matching an upper bound of Indyk [2001]. We also show that the very fast 2-independent multiply-shift scheme of Dietzfelbinger [1996] fails badly in both applications....

  13. The Scottish Independence Referendum and After

    Directory of Open Access Journals (Sweden)

    Michael Keating

    2015-04-01

    Full Text Available The Scottish independence referendum on 18 September 2014 produced an apparently decisive result, with 45 per cent for independence and 55 per cent against. Yet, it has not settled the constitutional issue. There was a huge public engagement in the campaign, which has left a legacy for Scottish and UK politics. Scotland has been reinforced as a political community. The losing Yes side has emerged in better shape and more optimistic, while the winners have struggled to formulate the better autonomy package they had promised. Public opinion continues to favour maximum devolution short of independence. Scotland is a case of the kind of spatial rescaling that is taking place more generally across Europe, as new forms of statehood and of sovereignty evolve. Scottish public opinion favours more self-government but no longer recognizes the traditional nation-state model presented in the referendum question.

  14. Independent events in elementary probability theory

    Science.gov (United States)

    Csenki, Attila

    2011-07-01

    In Probability and Statistics taught to mathematicians as a first introduction or to a non-mathematical audience, joint independence of events is introduced by requiring that the multiplication rule is satisfied. The following statement is usually tacitly assumed to hold (and, at best, intuitively motivated): quote specific-use="indent"> If the n events E 1, E 2, … , E n are jointly independent then any two events A and B built in finitely many steps from two disjoint subsets of E 1, E 2, … , E n are also independent. The operations 'union', 'intersection' and 'complementation' are permitted only when forming the events A and B. quote>Here we examine this statement from the point of view of elementary probability theory. The approach described here is accessible also to users of probability theory and is believed to be novel.

  15. Linear independence of localized magnon states

    International Nuclear Information System (INIS)

    Schmidt, Heinz-Juergen; Richter, Johannes; Moessner, Roderich

    2006-01-01

    At the magnetic saturation field, certain frustrated lattices have a class of states known as 'localized multi-magnon states' as exact ground states. The number of these states scales exponentially with the number N of spins and hence they have a finite entropy also in the thermodynamic limit N → ∞ provided they are sufficiently linearly independent. In this paper, we present rigorous results concerning the linear dependence or independence of localized magnon states and investigate special examples. For large classes of spin lattices, including what we call the orthogonal type and the isolated type, as well as the kagome, the checkerboard and the star lattice, we have proven linear independence of all localized multi-magnon states. On the other hand, the pyrochlore lattice provides an example of a spin lattice having localized multi-magnon states with considerable linear dependence

  16. Comment on atomic independent-particle models

    International Nuclear Information System (INIS)

    Doda, D.D.; Gravey, R.H.; Green, A.E.S.

    1975-01-01

    The Hartree-Fock-Slater (HFS) independent-particle model in the form developed by Hermann and Skillman (HS) and the Green, Sellin, and Zachor (GSZ) analytic independent-particle model are being used for many types of applications of atomic theory to avoid cumbersome, albeit more rigorous, many-body calculations. The single-electron eigenvalues obtained with these models are examined and it is found that the GSZ model is capable of yielding energy eigenvalues for valence electrons which are substantially closer to experimental values than are the results of HS-HFS calculations. With the aid of an analytic representation of the equivalent HS-HFS screening function, the difficulty with this model is identified as a weakness of the potential in the neighborhood of the valence shell. Accurate representations of valence states are important in most atomic applications of the independent-particle model

  17. Company profile: Big changes revive independent's profits

    International Nuclear Information System (INIS)

    Tippee, B.

    1996-01-01

    In 4 years' time, American Exploration has changed from an aggressive acquirer and manager of producing properties for institutional investors into a geographically focused independent producer dedicated to making money by finding and producing oil and gas. Through its adaptations to unexpectedly stagnant oil prices, American Exploration reflects the type of top-to-bottom changes many independent producers have made to survive a brutal decade. It also demonstrates that an independent producer can prosper in the absence of ever-rising prices: the company reported net income of $3.9 million last year following a $54.8 million loss--much of it related to an accounting change--in 1994 and a string of losses before that. In an interview with Oil and Gas Journal, Andrews discussed his company's transformation and financial turnaround, his new appreciation for the balance between capital and technology, and future directions of his company and industry

  18. Risk management for independent power projects

    International Nuclear Information System (INIS)

    Owen, J.L.

    1993-01-01

    Independent Power, where electric utilities or other bulk electric power users contract with individual electric power generation facilities to meet their projected long term power needs, has grown dramatically over the past ten years or more. This concept, to contract with Independent Power Producers (IPP), is not a new concept and in fact goes back to the early formation of the electric power industry in this country and worldwide. Successful Risk Management is the foundation for ultimate project completion and operation in fulfilling the expectations of all parties. The primary risks associated with the development of Independent Power projects include: predicting long term fuel availability and cost; predicting long term price for the deliverable of electricity; site selection, site characteristics and permitting; innovative or evolving technology; project execution (design and construction), and; lifetime O ampersand M costs and plant reliability. This paper focuses on the risks inherent in the development of IPPs and addresses the management of these risks

  19. Hypoxia increases pulmonary arterial thromboxane receptor internalization independent of receptor sensitization.

    Science.gov (United States)

    Fediuk, J; Sikarwar, A S; Lizotte, P P; Hinton, M; Nolette, N; Dakshinamurti, S

    2015-02-01

    Persistent Pulmonary Hypertension of the Newborn (PPHN) is characterized by sustained vasospasm and an increased thromboxane:prostacyclin ratio. Thromboxane (TP) receptors signal via Gαq to mobilize IP3 and Ca(2+), causing pulmonary arterial constriction. We have previously reported increased TP internalization in hypoxic pulmonary arterial (PA) myocytes. Serum-deprived PA myocytes were grown in normoxia (NM) or hypoxia (HM) for 72 h. TP localization was visualized in agonist-naïve and -challenged NM and HM by immunocytochemistry. Pathways for agonist-induced TP receptor internalization were determined by inhibiting caveolin- or clathrin-mediated endocytosis, and caveolar fractionation. Roles of actin and tubulin in TP receptor internalization were assessed using inhibitors of tubulin, actin-stabilizing or -destabilizing agents. PKA, PKC or GRK activation and inhibition were used to determine the kinase responsible for post-agonist receptor internalization. Agonist-naïve HM had decreased cell surface TP, and greater TP internalization after agonist challenge. TP protein did not sort with caveolin-rich fractions. Inhibition of clathrin prevented TP internalization. Both actin-stabilizing and -destabilizing agents prevented TP endocytosis in NM, while normalizing TP internalization in HM. Velocity of TP internalization was unaffected by PKA activity, but PKC activation normalized TP receptor internalization in HM. GRK inhibition had no effect. We conclude that in hypoxic myocytes, TP is internalized faster and to a greater extent than in normoxic controls. Internalization of the agonist-challenged TP requires clathrin, dynamic actin and is sensitive to PKC activity. TP receptor trafficking and signaling in hypoxia are pivotal to understanding increased vasoconstrictor sensitivity. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Source independence and the EPR paradox

    International Nuclear Information System (INIS)

    Mould, R.A.

    1989-01-01

    It is shown that the lines of action between the photon pairs resulting from a positronium decay are not necessarily in line with the original positronium atom. It is also shown why this 'source-independent' effect is not normally observed, although it is observable in principle. Moreover our initial concerns and some conclusions as they bear on the theory of measurement in quantum mechanics are discussed. Source-independence is shown to give a satisfactory response to a special form of the Einstein-Podolsky-Rosen paradox involving pairs of position measurements. It also leads to a nonlocal relationship between position measurements that depends on the width of the position detectors

  1. Electric power statistics from independence to establishment

    International Nuclear Information System (INIS)

    1997-02-01

    This paper reports power statistics from independence to establishment pf KEPIC. It has the lists of electricity industry, electric equipment on the whole country power equipment at the independence and development of power facility, power generation about merit of power plants, demand according to types and use, power loss, charge for electric power distribution, power generation and generating cost, financial lists on income measurement and financing, meteorological phenomena and amount of rainfall electric power development, international statistics on major countries power generation and compare power rates with general price.

  2. Controleum - an independently extensible control system

    DEFF Research Database (Denmark)

    Jensen, Martin Lykke Rytter

    2014-01-01

    challenging kind of system to design for independent extension. This thesis presents two new software technologies that improve the extensibility of control systems: First, the concept of dynamic links is introduced and Decouplink – an implementation of dynamic links for Java - is presented. Dynamic links...... is introduced, and an implementation is presented. The extensible controller is a component framework designed to automatically resolve conflicts among mutually unaware components in a control system. The solution is based on the idea that independent components implement different kinds of control concerns...

  3. THE RIGHT TO AN INDEPENDENT COURT

    Directory of Open Access Journals (Sweden)

    ALIN-GHEORGHE GAVRILESCU

    2011-04-01

    Full Text Available The independence of the court is essential of state of rule, to maintain the stability in juridical intercourse, for the existence of a constitutional democracy achieved through a warranty of the necessary objectivity for the steady and legal settlement of the causes deducted to the trial and the achievement of a fair trial. The article emphasizes the main international juridical tools in which independence of justice is reflected, achieving an examination of judicial practice of European instance as well as an analysis of this principle as it is regulated by Romanian justice.

  4. Conserved quantities in background independent theories

    Energy Technology Data Exchange (ETDEWEB)

    Markopoulou, Fotini [Perimeter Institute for Theoretical Physics, 35 King Street North, Waterloo, Ontario N2J 2W9 (Canada); Department of Physics, University of Waterloo, Waterloo, Ontario N2L 3G1 (Canada)

    2007-05-15

    We discuss the difficulties that background independent theories based on quantum geometry encounter in deriving general relativity as the low energy limit. We follow a geometrogenesis scenario of a phase transition from a pre-geometric theory to a geometric phase which suggests that a first step towards the low energy limit is searching for the effective collective excitations that will characterize it. Using the correspondence between the pre-geometric background independent theory and a quantum information processor, we are able to use the method of noiseless subsystems to extract such coherent collective excitations. We illustrate this in the case of locally evolving graphs.

  5. Quantifying identifiability in independent component analysis

    DEFF Research Database (Denmark)

    Sokol, Alexander; Maathuis, Marloes H.; Falkeborg, Benjamin

    2014-01-01

    We are interested in consistent estimation of the mixing matrix in the ICA model, when the error distribution is close to (but different from) Gaussian. In particular, we consider $n$ independent samples from the ICA model $X = A\\epsilon$, where we assume that the coordinates of $\\epsilon......$ are independent and identically distributed according to a contaminated Gaussian distribution, and the amount of contamination is allowed to depend on $n$. We then investigate how the ability to consistently estimate the mixing matrix depends on the amount of contamination. Our results suggest...

  6. Survey of independent inventors: An overview

    Energy Technology Data Exchange (ETDEWEB)

    Whalley, P.

    1992-12-01

    Independent inventors are important but little-researched members of the US technical community. The survey reported on here is the first in modern times to attempt to provide a profile of the US independent inventor that goes beyond a single geographical or organizational locale. The report that follows provides an overview of the demographics, practices and concerns of the modern US inventor as represented by the members of leading US inventor organizations. It is by no means comprehensive but seeks to be indicative of the issues raised in the survey each which will be dealt with more comprehensively in future publications.

  7. Distributed Large Independent Sets in One Round On Bounded-independence Graphs

    OpenAIRE

    Halldorsson , Magnus M.; Konrad , Christian

    2015-01-01

    International audience; We present a randomized one-round, single-bit messages, distributed algorithm for the maximum independent set problem in polynomially bounded-independence graphs with poly-logarithmic approximation factor. Bounded-independence graphs capture various models of wireless networks such as the unit disc graphs model and the quasi unit disc graphs model. For instance, on unit disc graphs, our achieved approximation ratio is O((log(n)/log(log(n)))^2).A starting point of our w...

  8. 7 CFR 1221.122 - Independent evaluation.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Independent evaluation. 1221.122 Section 1221.122 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING... INFORMATION ORDER Sorghum Promotion, Research, and Information Order Promotion, Research, and Information...

  9. 7 CFR 1206.51 - Independent evaluation.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Independent evaluation. 1206.51 Section 1206.51 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING... INFORMATION Mango Promotion, Research, and Information Order Definitions Promotion, Research, and Information...

  10. Problems Identifying Independent and Dependent Variables

    Science.gov (United States)

    Leatham, Keith R.

    2012-01-01

    This paper discusses one step from the scientific method--that of identifying independent and dependent variables--from both scientific and mathematical perspectives. It begins by analyzing an episode from a middle school mathematics classroom that illustrates the need for students and teachers alike to develop a robust understanding of…

  11. Blind Detection of Independent Dynamic Components

    DEFF Research Database (Denmark)

    Hansen, Lars Kai; Larsen, Jan; Kolenda, Thomas

    2001-01-01

    In certain applications of independent component analysis (ICA) it is of interest to test hypotheses concerning the number of components or simply to test whether a given number of components is significant relative to a "white noise" null hypothesis. We estimate probabilities of such competing h...

  12. Quadratic independence of coordinate functions of certain ...

    Indian Academy of Sciences (India)

    ... are `quadratically independent' in the sense that they do not satisfy any nontrivial homogeneous quadratic relations among them. Using this, it is proved that there is no genuine compact quantum group which can act faithfully on C ( M ) such that the action leaves invariant the linear span of the above coordinate functions.

  13. Central bank independence and inflation revisited

    NARCIS (Netherlands)

    Klomp, Jeroen; de Haan, Jakob

    We re-examine the relationship between central bank independence (CBI), proxied by the central bank governor's turnover rate and an indicator based on central bank laws in place, and inflation using a random coefficient model with the Hildreth-Houck estimator for more than 100 countries in the

  14. Central bank independence and inflation revisited

    NARCIS (Netherlands)

    Klomp, J.G.; Haan, de J.

    2010-01-01

    We re-examine the relationship between central bank independence (CBI), proxied by the central bank governor's turnover rate and an indicator based on central bank laws in place, and inflation using a random coefficient model with the Hildreth-Houck estimator for more than 100 countries in the

  15. Complementary, substitution, and independence among tourist trips

    NARCIS (Netherlands)

    Middelkoop, van M.; Borgers, A.W.J.; Timmermans, H.J.P.

    1999-01-01

    The relationship between day trips, short breaks (2-4 days), and holidays (5+ days) has never been examined at the level of the individual consumer because surveys on day and overnight trips are typically conducted independently. In this article, both the stated and the inferred relationship between

  16. Environmental Influences on Independent Collaborative Play

    Science.gov (United States)

    Mawson, Brent

    2010-01-01

    Data from two qualitative research projects indicated a relationship between the type of early childhood setting and children's independent collaborative play. The first research project involved 22 three and four-year-old children in a daylong setting and 47 children four-year-old children in a sessional kindergarten. The second project involved…

  17. Endothelium-independent and endothelium-dependent ...

    African Journals Online (AJOL)

    This endothelium-independent relaxant effect was also sensitive to combination of 1H-[1,2,4]-oxadiazole-[4,3-á]-quinoxalin- 1-one (ODQ, 10 ìM, soluble guanylyl cyclase inhibitor) and N-[2-(p-Bromocinnamylamino)ethyl]-5-isoquinoline sulfonamide dihydrochloride (H89, 100 nM, Protein Kinase A inhibitor). Taken together ...

  18. Scale-Independent Relational Query Processing

    Science.gov (United States)

    Armbrust, Michael Paul

    2013-01-01

    An increasingly common pattern is for newly-released web applications to succumb to a "Success Disaster". In this scenario, overloaded database machines and resultant high response times destroy a previously good user experience, just as a site is becoming popular. Unfortunately, the data independence provided by a traditional relational…

  19. Independent Events in Elementary Probability Theory

    Science.gov (United States)

    Csenki, Attila

    2011-01-01

    In Probability and Statistics taught to mathematicians as a first introduction or to a non-mathematical audience, joint independence of events is introduced by requiring that the multiplication rule is satisfied. The following statement is usually tacitly assumed to hold (and, at best, intuitively motivated): If the n events E[subscript 1],…

  20. Independent midwifery practice: Opportunities and challenges | du ...

    African Journals Online (AJOL)

    A qualitative approach was used and midwives, who work in solo (independent) practice, were identified on the internet and via Facebook and invited to participate. Interviews and narrative reports were used for data gathering. Although passionate about their jobs, the most challenging aspect for the midwives, was inter- ...

  1. Introducing Disjoint and Independent Events in Probability.

    Science.gov (United States)

    Kelly, I. W.; Zwiers, F. W.

    Two central concepts in probability theory are those of independence and mutually exclusive events. This document is intended to provide suggestions to teachers that can be used to equip students with an intuitive, comprehensive understanding of these basic concepts in probability. The first section of the paper delineates mutually exclusive and…

  2. Independence and Interdependence in Diverse Cultural Contexts.

    Science.gov (United States)

    Killen, Melanie; Wainryb, Cecilia

    2000-01-01

    Argues that the individualistic-collectivistic dichotomy results in mislabeling both cultures and individuals. Discusses ways in which individualistic concerns with independence and collectivistic concerns with interdependence coexist in Western and non-Western cultures. Outlines a theoretical framework explaining the coexistence of diverse social…

  3. Hegemony, Big Money and Academic Independence

    Science.gov (United States)

    Anderson, Tim

    2010-01-01

    This article considers whether a threat is posed to academic independence in corporate universities by the United States Studies Centre (USSC) at the University of Sydney. The USSC rapidly worked its way into Australia's oldest university, building a unique governance structure in which a private business lobby vets senior academics and controls…

  4. 12 CFR 34.45 - Appraiser independence.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 1 2010-01-01 2010-01-01 false Appraiser independence. 34.45 Section 34.45 Banks and Banking COMPTROLLER OF THE CURRENCY, DEPARTMENT OF THE TREASURY REAL ESTATE LENDING AND... appraiser shall be engaged directly by the regulated institution or its agent, and have no direct or...

  5. Comparing BV solutions of rate independent processes

    Czech Academy of Sciences Publication Activity Database

    Krejčí, Pavel; Recupero, V.

    2014-01-01

    Roč. 21, č. 1 (2014), s. 121-146 ISSN 0944-6532 R&D Projects: GA ČR GAP201/10/2315 Institutional support: RVO:67985840 Keywords : variational inequalities * rate independence * convex sets Subject RIV: BA - General Mathematics Impact factor: 0.552, year: 2014 http://www.heldermann.de/JCA/JCA21/JCA211/jca21006.htm

  6. Deforestation since independence: A quantitative assessment of ...

    African Journals Online (AJOL)

    Deforestation since independence: A quantitative assessment of four decades of land-cover change in Malawi. ... pressure and demographic factors are important predictors of deforestation rate within our study area. Keywords: afforestation, Africa, deforestation, drivers, land-use change, reforestation, rural, urban ...

  7. 12 CFR 722.5 - Appraiser independence.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Appraiser independence. 722.5 Section 722.5 Banks and Banking NATIONAL CREDIT UNION ADMINISTRATION REGULATIONS AFFECTING CREDIT UNIONS APPRAISALS... interest, financial or otherwise, in the property. If the only qualified persons available to perform an...

  8. Independence requirements for anti-corruption institutions

    African Journals Online (AJOL)

    The Court's approach and these apparent requirements are compared with current provisions for political 'independence' of anti-corruption agencies in Australia and Indonesia, raising, in particular, an assessment of the arguments for and against (a) the need for an anti-corruption investigative agency to be separate from ...

  9. The Politics of Central Bank Independence

    NARCIS (Netherlands)

    de Haan, J.; Eijffinger, Sylvester

    2016-01-01

    This paper reviews recent research on the political economy of monetary policy-making, both by economists and political scientists. The traditional argument for central bank independence (CBI) is based on the desire to counter inflationary biases. However, studies in political science on the

  10. Outer-2-independent domination in graphs

    Indian Academy of Sciences (India)

    Outer-2-independent domination in graphs. MARCIN KRZYWKOWSKI1,2,∗, DOOST ALI MOJDEH3 and MARYEM RAOOFI4. 1Department of Pure and Applied Mathematics, University of Johannesburg,. Johannesburg, South Africa. 2Faculty of Electronics, Telecommunications and Informatics, Gdansk University.

  11. Chains versus Independents: Newspaper and Market Characteristics.

    Science.gov (United States)

    Hale, F. Dennis

    A study examined the marketing differences between large chain newspapers and small chain and independent newspapers by analyzing differences in characteristics of the newspapers, patterns of circulation, economic and social conditions of the market, and competition from other print media. The 200 newspapers studied--113 large chain and 87 small…

  12. Assessing the Cost of Energy Independence

    NARCIS (Netherlands)

    Jongerden, M.R.; Hüls, Jannik; Haverkort, Boudewijn R.H.M.; Remke, Anne Katharina Ingrid

    Battery management strategies that reserve a certain capacity for power outages are able to increase the energy independence of a smart home. However, such strategies come at a certain cost, since these storage strategies are less flexible and energy from the grid may have to be bought at a high

  13. Independent component analysis for understanding multimedia content

    DEFF Research Database (Denmark)

    Kolenda, Thomas; Hansen, Lars Kai; Larsen, Jan

    2002-01-01

    Independent component analysis of combined text and image data from Web pages has potential for search and retrieval applications by providing more meaningful and context dependent content. It is demonstrated that ICA of combined text and image features has a synergistic effect, i.e., the retrieval...

  14. Classification error of the thresholded independence rule

    DEFF Research Database (Denmark)

    Bak, Britta Anker; Fenger-Grøn, Morten; Jensen, Jens Ledet

    We consider classification in the situation of two groups with normally distributed data in the ‘large p small n’ framework. To counterbalance the high number of variables we consider the thresholded independence rule. An upper bound on the classification error is established which is taylored...

  15. Independent regulatory authorities in European electricity market

    DEFF Research Database (Denmark)

    Olsen, Ole Jess; Larsen, Anders; Sørensen, Eva Moll

    2006-01-01

    Liberalisation of the electricity market has taken place in most European countries within the last decade. It is considered a precondition of successful liberalisation to establish so-called independent regulatory authorities. In this article, we compare the status and practice of them in 16...

  16. Across the Desk: Teaching Through Independent Study

    Science.gov (United States)

    Lamdin, Lois; Worby, Diana

    1976-01-01

    Independent study is addressed as a creative and alternative mode of learning. Its unique advantages and strengths are examined along with its planning and structure, the student/instructor interaction, the use of learning resources, examples of disciplinary and interdisciplinary approaches, the products of such study, and methods of evaluation.…

  17. Temperature-independent resistor for microelectronic circuits

    Science.gov (United States)

    Aegerter, S.; Libby, W. F.

    1970-01-01

    Heat treating insulating crystals in gaseous hydrogen atmosphere produce resistive device which is temperature-independent from 77 to 295 degrees K. Increasing the concentration of hydrogen within the crystal yields semiconductor, hybrid, and metallic conduction characteristics which are combined with a depletion layer at the surface.

  18. The Next Marketing Handbook for Independent Schools.

    Science.gov (United States)

    Cowan, Rick, Ed.

    Suggestions for marketing independent schools are presented in this handbook, which revolves around the basic marketing model of defining mission/strategy, using the "5 P's" (product/services, price, place, production/delivery, promotion) and monitoring. Chapters by 18 contributors offer information on the following topics: basic marketing theory,…

  19. Independent regulatory authorities in European electricity markets

    International Nuclear Information System (INIS)

    Larsen, Anders; Pedersen, Lene Holm; Sorensen, Eva Moll; Olsen, Ole Jess

    2006-01-01

    Liberalisation of the electricity market has taken place in most European countries within the last decade. It is considered a precondition of successful liberalisation to establish so-called independent regulatory authorities. In this article, we compare the status and practice of them in 16 European countries, and discuss the relationship between the organisation of the regulation and the market outcome

  20. Morphology Independent Learning in Modular Robots

    DEFF Research Database (Denmark)

    Christensen, David Johan; Bordignon, Mirko; Schultz, Ulrik Pagh

    2009-01-01

    speed its modules independently and in parallel adjust their behavior based on a single global reward signal. In simulation, we study the learning strategy’s performance on different robot configurations. On the physical platform, we perform learning experiments with ATRON robots learning to move as fast...

  1. Morphology Independent Learning in Modular Robots

    DEFF Research Database (Denmark)

    Christensen, David Johan; Bordignon, Mirko; Schultz, Ulrik Pagh

    2009-01-01

    speed its modules independently and in parallel adjust their behavior based on a single global reward signal. In simulation, we study the learning strategy?s performance on different robot con?gurations. On the physical platform, we perform learning experiments with ATRON robots learning to move as fast...

  2. Independence and Interdependence in Early Childhood Services

    Science.gov (United States)

    Whitington, Victoria

    2004-01-01

    It is through culture that children make sense of their worlds (Trevarthen, 1998). Cross- cultural models show that families are likely to primarily foster either independence or interdependence in their children (Gonzalez-Mena, 1997; Greenfield, 1994). Young children are likely to pay the "price of acculturation" when they enter early…

  3. Development of independent walking in toddlers

    NARCIS (Netherlands)

    Ivanenko, Yuri P; Dominici, Nadia; Lacquaniti, Francesco

    Surprisingly, despite millions of years of bipedal walking evolution, the gravity-related pendulum mechanism of walking does not seem to be implemented at the onset of independent walking, requiring each toddler to develop it. We discuss the precursor of the mature locomotor pattern in infants as an

  4. BV solutions of rate independent differential inclusions

    Czech Academy of Sciences Publication Activity Database

    Krejčí, Pavel; Recupero, V.

    2014-01-01

    Roč. 139, č. 4 (2014), s. 607-619 ISSN 0862-7959 R&D Projects: GA ČR GAP201/10/2315 Institutional support: RVO:67985840 Keywords : differential inclusion * stop operator * rate independence * convex set Subject RIV: BA - General Mathematics http://hdl.handle.net/10338.dmlcz/144138

  5. Body Weight Independently Affects Articular Cartilage Catabolism

    Directory of Open Access Journals (Sweden)

    W. Matt Denning, Jason G. Winward, Michael Becker Pardo, J. Ty Hopkins, Matthew K. Seeley

    2015-06-01

    Full Text Available Although obesity is associated with osteoarthritis, it is unclear whether body weight (BW independently affects articular cartilage catabolism (i.e., independent from physiological factors that also accompany obesity. The primary purpose of this study was to evaluate the independent effect of BW on articular cartilage catabolism associated with walking. A secondary purpose was to determine how decreased BW influenced cardiovascular response due to walking. Twelve able-bodied subjects walked for 30 minutes on a lower-body positive pressure treadmill during three sessions: control (unadjusted BW, +40%BW, and -40%BW. Serum cartilage oligomeric matrix protein (COMP was measured immediately before (baseline and after, and 15 and 30 minutes after the walk. Heart rate (HR and rate of perceived exertion (RPE were measured every three minutes during the walk. Relative to baseline, average serum COMP concentration was 13% and 5% greater immediately after and 15 minutes after the walk. Immediately after the walk, serum COMP concentration was 14% greater for the +40%BW session than for the -40%BW session. HR and RPE were greater for the +40%BW session than for the other two sessions, but did not differ between the control and -40%BW sessions. BW independently influences acute articular cartilage catabolism and cardiovascular response due to walking: as BW increases, so does acute articular cartilage catabolism and cardiovascular response. These results indicate that lower-body positive pressure walking may benefit certain individuals by reducing acute articular cartilage catabolism, due to walking, while maintaining cardiovascular response.

  6. Cultural Relativism: Occupation and Independence Reconsidered.

    Science.gov (United States)

    Whiteford, Gail Elizabeth; Wilcock, Ann Allart

    2000-01-01

    A study focused on the experiences of 22 occupational therapy students working with people from different social and cultural backgrounds in New Zealand over a 3-year period. Results highlight issues about how occupation and independence are conceptualized across cultures. (Contains 102 references.) (JOW)

  7. Environmental liability and the independent contractor

    International Nuclear Information System (INIS)

    Gilmour, B.S.

    1999-01-01

    The provisions of the Environmental Protection and Enhancement Act (EPEA) regarding the relationship between a company and an independent contractor were reviewed. The EPEA was introduced in September 1993 and significantly altered the environmental laws in the province of Alberta. The provisions of the EPEA that apply to the petroleum industry are conservation and reclamation as well as provisions concerning release of substances, contaminated sites and penalties. Companies that pollute may be held liable for reclamation, even if the work was carried out by an independent contractor and despite the fact that the independent contractor is not an employee of the company. Under the current EPEA laws, companies may not be able to effectively shift responsibility for environmental liabilities to independent contractors even where the contractor was negligent. This paper presented suggestions regarding contractor agreements and due diligence to help minimize the risk of liability to companies. The paper also discussed the following two types of liabilities under the EPEA's harmful substances section: (1) the obligation to clean up an affected area, and (2) fines and penalties that may be imposed when an offence is committed

  8. Leaving home for college and gaining independence

    NARCIS (Netherlands)

    Mulder, C.H.; Clark, W.A.V.

    2002-01-01

    As more and more young US adults attend college it has become an increasingly important filter in the process of becoming an independent household. Now for a large number of young adults living in the USA, living away at college is a first step in the process of gaining residential and economic

  9. Enhanced temperature-independent magnetoresistance below the ...

    Indian Academy of Sciences (India)

    The film exhibits a large nearly temperature-independent magnetoresistance around 99% in the temperature regime below p. The zero field-cooled (ZFC) and field-cooled (FC) magnetization data at 50 Oe shows irreversibility between the ZFC and FC close to the ferromagnetic transition temperature c = 250 K. The ZFC ...

  10. Parental Involvement in Children's Independent Music Lessons

    Science.gov (United States)

    Upitis, Rena; Abrami, Philip C.; Brook, Julia; King, Matthew

    2017-01-01

    The purpose of the study was to examine types of parental involvement associated with independent music lessons. A self-report survey was designed to explore parent characteristics, parental goals, students' musical progress, the teacher-student relationship, the practice environment, and parent behaviours during practice sessions. The extent to…

  11. The Independent Music Teacher: Practice and Preparation.

    Science.gov (United States)

    Uszler, Marienne

    1996-01-01

    Provides a concise overview of the working conditions and challenges faced by independent music teachers (IMT). Most IMTs function in a number of capacities, as performer, teacher, and entrepreneur. Discusses changing trends in employment, including computer technology and the move for national certification. (MJP)

  12. transformation of independent variables in polynomial regression ...

    African Journals Online (AJOL)

    Ada

    preferable when possible to work with a simple functional form in transformed variables rather than with a more complicated form in the original variables. In this paper, it is shown that linear transformations applied to independent variables in polynomial regression models affect the t ratio and hence the statistical ...

  13. Jan Culik on the Scottish independence referendum

    OpenAIRE

    Culik, Jan

    2014-01-01

    A live interview with Jan Culik on the results and the political circumstances of the referendum on Scottish independence, broadcast from the BBC Pacific Quay studios. The interview was transmitted on Friday 19th September, 2014, by the nationwide Czech public service Radio (Radiozurnal) from 10 to 11 am.

  14. Independence Day 2004 (ID04) / Raul Hindov

    Index Scriptorium Estoniae

    Hindov, Raul

    2004-01-01

    Ülevaade 20.-22. veebruarini 2004 toimunud kaugluurepatrullide rännaku ja sõdurioskuste kompleksõppusest ID04 (Independence Day 2004 - Iseseisvuspäev 2004), millel osales 25 patrullvõistlusteks valmistuvat meest ja naist

  15. Independent variables in 3 + 1 Regge calculus

    International Nuclear Information System (INIS)

    Tuckey, P.A.

    1989-01-01

    The space of metrics in 3+1 Regge calculus is discussed, and the problems of counting its dimensions, and of finding independent variables to parametrise the space, are addressed. The most general natural class of metrics is considered first, and bounds on its dimension are obtained, although no good parametrisations are found. The relationship between these metrics and those used in canonical Regge calculus is shown, and this leads to an interesting result via the Bianchi identities. A restricted class of metrics is then considered and independent variables, which parametrise these metrics and which may be computationally convenient, are given. The dimension of this space of metrics gives an improved lower bound for the dimension of the general space. (author)

  16. Energy independent optical potentials: construction and limitations

    International Nuclear Information System (INIS)

    Hussein, M.S.; Moniz, E.J.

    1983-11-01

    Properties of the energy-independent potential U sup(-) which is wave-function-equivalent to the usual optical potential U(E) are constructed and examined. A simple procedure is presented for constructing U sup(-) in the uniform medium, and physical examples are discussed. The general result for finite systems, a recursive expansion in powers of U(E), is used to investigate the multiple scattering expansion of U sup(-); the energy-independent potential is found to have serious short-comings for direct microscopic construction or phenomenological parametrization. The microscopic theory, as exemplified here by the multiple scattering approach, does not lead to a reliable approximation scheme. Phenomenological approaches to U sup(-) are unattractive because the physics does not guide the parametrization effectively: the structure of the nonlocality is not tied directly to the dynamics; Im U sup(-) changes sign; different elements of the physics, separate in U(E), are completely entangled in U sup(-). (Author) [pt

  17. Marginalia. The Literary Independence of Spanish America

    Directory of Open Access Journals (Sweden)

    Juan Guillermo Gómez García

    2010-12-01

    Full Text Available This article discusses some of the characteristic problems and issues of the so-called “literary independence” of Spanish America in the light of its political emancipation from Spain. This topic goes beyond the temporal framework or the periodization of the wars of independence; instead, it covers the entire nineteenth century and part of the twentieth, and appears discontinuously and non-simultaneously in the different nations. The path followed by Spanish American literature was filled with vicissitudes,manifestations, and regressions of diverse types. The paper specifically analyzes La biblioteca americana and El repertorio americano by the Venezuelan, Andrés Bello, and Juan García del Río, a native of Cartagena, as well as the role of the young Argentinean Domingo F. Sarmiento, author of Facundo, in the genesis and first outlines of an independent Spanish American “literary expression”.

  18. From independence to expansion and back again

    DEFF Research Database (Denmark)

    Christiani, Tobias Lybecker; Pagh, Rasmus; Thorup, Mikkel

    2015-01-01

    We consider the following fundamental problems: • Constructing k-independent hash functions with a spacetime tradeoff close to Siegel’s lower bound. • Constructing representations of unbalanced expander graphs having small size and allowing fast computation of the neighbor function. It is not hard...... to show that these problems are intimately connected in the sense that a good solution to one of them leads to a good solution to the other one. In this paper we exploit this connection to present efficient, recursive constructions of k-independent hash functions (and hence expanders with a small...... representation). While the previously most efficient construction (Thorup, FOCS 2013) needed time quasipolynomial in Siegel’s lower bound, our time bound is just a logarithmic factor from the lower bound....

  19. Recent experiences with independent power projects

    International Nuclear Information System (INIS)

    Kline, R.H.; Fitzowitch, J.R.; Dalla-Longa, L.

    1999-01-01

    New opportunities are making it possible to develop independent power projects involving partnerships with the electric power industry, and the petroleum and natural gas industry . This paper described those opportunities, the impediments and the risks involved. Mercury Electric Corp. has been involved in power projects at remote gas field and oil field sites where they use of a turbogenerator which runs on flare gas to generate electricity. TransCanada Power's involvement in independent power projects includes the supply and transport of gas and their ability to provide gas fired combined cycle technology. They are involved in a project at Hermiston, Oregon and also in a cogeneration project in Medicine Hat, Alberta. The CanCarb City of Medicine Hat project makes use of waste heat at an industrial facility. 11 figs

  20. Designing platform independent mobile apps and services

    CERN Document Server

    Heckman, Rocky

    2016-01-01

    This book explains how to help create an innovative and future proof architecture for mobile apps by introducing practical approaches to increase the value and flexibility of their service layers and reduce their delivery time. Designing Platform Independent Mobile Apps and Services begins by describing the mobile computing landscape and previous attempts at cross platform development. Platform independent mobile technologies and development strategies are described in chapter two and three. Communication protocols, details of a recommended five layer architecture, service layers, and the data abstraction layer are also introduced in these chapters. Cross platform languages and multi-client development tools for the User Interface (UI) layer, as well as message processing patterns and message routing of the Service Int rface (SI) layer are explained in chapter four and five. Ways to design the service layer for mobile computing, using Command Query Responsibility Segregation (CQRS) and the Data Abstraction La...

  1. Boosting orthographic learning during independent reading

    DEFF Research Database (Denmark)

    Nielsen, Anne-Mette Veber

    2016-01-01

    . The present training study was conducted to assess experimentally whether this relation between prior orthographic knowledge and orthographic learning while reading is causal by assessing whether instruction designed to increase sublexical orthographic knowledge would facilitate orthographic learning during......Research has shown that phonological decoding is critical for orthographic learning of new words during independent reading. Moreover, correlational studies have demonstrated that the strength of orthographic learning is related to the orthographic knowledge with which readers approach a text...... independent reading. A group of Danish-speaking third graders (n = 21) was taught conditional spelling patterns conforming to the opaque Danish writing system, with emphasis on how to map the spellings onto their pronunciations. A matched control group (n = 21) received no treatment. Both groups were exposed...

  2. 30 CFR 45.4 - Independent contractor register.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Independent contractor register. 45.4 Section... ADMINISTRATIVE REQUIREMENTS INDEPENDENT CONTRACTORS § 45.4 Independent contractor register. (a) Each independent contractor shall provide the production-operator in writing the following information: (1) The independent...

  3. Independent technical review of the Pinellas Plant

    Energy Technology Data Exchange (ETDEWEB)

    1994-07-01

    This report documents an Independent Technical Review (ITR) of facilities, organizations, plans, activities and various other elements required to successfully transition the Pinellas Plant from Defense Program (DP) funded operation to either community developed reuse or safe deactivation leading to decontamination and decommissioning (D&D). The review was conducted at the request of the Department of Energy (DOE) Deputy Assistant Secretary for Facility Transition and Management (EM-60) and is a consensus of the nine member ITR Team.

  4. Providing Device Independence to Mobile Services

    OpenAIRE

    Nylander, Stina; Bylund, Markus

    2002-01-01

    People want user interfaces to services that are functional and well suited to the device they choose for access. To provide this, services must be able to offer device specific user interfaces for the wide range of devices available today. We propose to combine the two dominant approaches to platform independence, "Write Once, Run Every-where™" and "different version for each device", to create multiple device specific user interfaces for mobile services. This gives possibilities to minimize...

  5. Primary Teachers’ Burnout in Qatar Independent Schools

    OpenAIRE

    Alloh, Maymona Mohamed

    2017-01-01

    The present research aims at investigating the burnout levels among primary teachers in independent (government) schools in Qatar. It also intends to investigate if there are significant differences in the level of burnout attributed to some demographic characteristics. The third version of the most commonly used burnout scale; Maslach Burnout Inventory-Educators Survey (MBI-ES), was utilized in order to measure participants’ burnout level. A total of 1657 participants responded and completed...

  6. The United States toward Energy Independence?

    International Nuclear Information System (INIS)

    Nardon, Laurence

    2013-01-01

    The U.S.'s exploitation of 'unconventional' domestic oil reserves is reviving its economy. It will also have effects on the country's energy independence and thus its geopolitical position. While it is unlikely that the relationship between Washington and the Middle East region will be fundamentally altered, the U.S.'s relationships with China, Russia, and Europe could be affected. The United States will have to incorporate these changes into its global strategies

  7. Sustainability, Materiality and Independent External Assurance

    OpenAIRE

    Jones, Peter; Bown, Robin; Hillier, David; Comfort, Daphne

    2017-01-01

    This chapter offers a preliminary examination of how the UK's leading food retailers are reporting on sustainability and of the role of materiality and external assurance in their reporting processes. Food retailing is by far the largest, and arguably the most fiercely competitive, sector within the UK retail economy. The chapter examines the current sustainability issues being addressed by the UK's leading food retailers, if and how they embraced materiality and commissioned independent exte...

  8. Charge-independence-breaking in the triton

    International Nuclear Information System (INIS)

    Gloeckle, W.; Lee, T.S.H.; Wiringa, R.B.

    1990-01-01

    We find the effect of the observed charge-independence-breaking in 1 S 0 nucleon-nucleon scattering on the binding energy of the triton to be of order 80 keV. When corrections for this effect are made in an 18-channel momentum-space Faddeev calculation, we find the Paris and Argonne v 14 potentials triton binding energies that differ by only 20 keV

  9. Hypoxia independent drivers of melanoma angiogenesis

    Directory of Open Access Journals (Sweden)

    Svenja eMeierjohann

    2015-05-01

    Full Text Available Tumor angiogenesis is a process which is traditionally regarded as the tumor`s response to low nutrient supply occurring under hypoxic conditions. However, hypoxia is not a prerequisite for angiogenesis. The fact that even single tumor cells or small tumor cell aggregates are capable of attracting blood vessels reveals the early metastatic capability of tumor cells. This review sheds light on the hypoxia independent mechanisms of tumor angiogenesis in melanoma.

  10. Recognition of an Independent Self-Consciousness

    DEFF Research Database (Denmark)

    Bjerre, Henrik Jøker

    2009-01-01

    Hegel's concept in the Phenomenology of the Spirit of the "recognition of an independent self-consciousness" is investigated as a point of separation for contemporary philosophy of recognition. I claim that multiculturalism and the theories of recognition (such as Axel Honneth's) based on empiric...... psychology neglect or deny crucial metaphysical aspects of the Hegelian legacy. Instead, I seek to point at an additional, "spiritual", level of recognition, based on the concept of the subject in Lacanian psychoanalysis....

  11. Search-Order Independent State Caching

    DEFF Research Database (Denmark)

    Evangelista, Sami; Kristensen, Lars Michael

    2009-01-01

    State caching is a memory reduction technique used by model checkers to alleviate the state explosion problem. It has traditionally been coupled with a depth-first search to ensure termination.We propose and experimentally evaluate an extension of the state caching method for general state...... exploring algorithms that are independent of the search order (i.e., search algorithms that partition the state space into closed (visited) states, open (to visit) states and unmet states)....

  12. Bibliographic information interchange with data independence

    International Nuclear Information System (INIS)

    Macedo, L.F.P. de

    1980-01-01

    A technique for bibliographic information processing, at the standardized interchange format ISO 2709 or ANSI Z39.2, which allows to obtain programs with data independence is developed. A format definition language and manipulation commands which enable data storage and retrieval at the logical level are specified. With this technique it is possible to implement programs which can accept data from any information system, reducing, therefore, the requirements of a common bibliographic information interchange format. (Author) [pt

  13. Parallel Device-Independent Quantum Key Distribution

    OpenAIRE

    Jain, Rahul; Miller, Carl A.; Shi, Yaoyun

    2017-01-01

    A prominent application of quantum cryptography is the distribution of cryptographic keys with unconditional security. Recently, such security was extended by Vazirani and Vidick (Physical Review Letters, 113, 140501, 2014) to the device-independent (DI) scenario, where the users do not need to trust the integrity of the underlying quantum devices. The protocols analyzed by them and by subsequent authors all require a sequential execution of N multiplayer games, where N is the security parame...

  14. The local authority rating of independent generators

    International Nuclear Information System (INIS)

    Chapman, G.C.

    1991-01-01

    A brief history of the rating is given covering the public utilities. Formula rating of the nationalised electricity supply industry is described with independent generators' rates, the effect of privatisation and the longer term outlook considered. The need to convince the UK government that power generating machinery should no more be rated than any manufacturing or process machinery, and that all power producers should be treated the same is noted. (Author)

  15. Independent assessment for new nuclear reactor safety

    Directory of Open Access Journals (Sweden)

    D'Auria Francesco

    2017-01-01

    Full Text Available A rigorous framework for safety assessment is established in all countries where nuclear technology is used for the production of electricity. On the one side, industry, i.e. reactor designers, vendors and utilities perform safety analysis and demonstrate consistency between results of safety analyses and requirements. On the other side, regulatory authorities perform independent assessment of safety and confirm the acceptability of safety of individual reactor units. The process of comparing results from analyses by reactor utilities and regulators is very complex. The process is also highly dependent upon mandatory approaches pursued for the analysis and from very many details which required the knowledge of sensitive proprietary data (e.g. spacer designs. Furthermore, all data available for the design, construction and operation of reactors produced by the nuclear industry are available to regulators. Two areas for improving the process of safety assessment for individual Nuclear Power Plant Units are identified: New details introduced by industry are not always and systematically requested by regulators for the independent assessment; New analytical techniques and capabilities are not necessarily used in the analyses by regulators (and by the industry. The established concept of independent assessment constitutes the way for improving the process of safety assessment. This is possible, or is largely facilitated, by the recent availability of the so-called Best Estimate Plus Uncertainty approach.

  16. Management Technology of Students’ Independent Work

    Directory of Open Access Journals (Sweden)

    Melis K. Asanaliev

    2012-09-01

    Full Text Available The researchers are convinced that for an intensification of educational process in higher education institution it is necessary development of essentially new approaches, forms and the methods of social and pedagogical interaction adequate to new requirements, new pedagogical thinking. Among them we can choose the methods of social and psychological training (SPT which received their development in experimental psychology by synthesis of wide practical experience educational, creative, administrative, and other types of interrelation between people. These methods conditionally divide on: debatable (group discussion, analysis of a situation of a moral choice, game methods (didactic, creative, role-playing games, sensitive training (training of interpersonal sensitivity which are formations of independent informative activity of students on the basis of modern technologies, as the mechanism of improvement of independent work. Researches are expressed in search and finding enough effective forms and means of activation of educational and informative process of preparation of young teachers of vocational training, theoretically and practically prepared in the field of the independent informative activity, use the modern technology of training and its further realization in work with students of technical secondary. It is offered the model of the organization and application in educational process of the complex of these methods in contents complex of training programs of systems of tasks as one of ways of formation of social and psychological culture of future teacher.

  17. Fully device-independent conference key agreement

    Science.gov (United States)

    Ribeiro, Jérémy; Murta, Gláucia; Wehner, Stephanie

    2018-02-01

    We present a security analysis of conference key agreement (CKA) in the most adversarial model of device independence (DI). Our protocol can be implemented by any experimental setup that is capable of performing Bell tests [specifically, the Mermin-Ardehali-Belinskii-Klyshko (MABK) inequality], and security can in principle be obtained for any violation of the MABK inequality that detects genuine multipartite entanglement among the N parties involved in the protocol. As our main tool, we derive a direct physical connection between the N -partite MABK inequality and the Clauser-Horne-Shimony-Holt (CHSH) inequality, showing that certain violations of the MABK inequality correspond to a violation of the CHSH inequality between one of the parties and the other N -1 . We compare the asymptotic key rate for device-independent conference key agreement (DICKA) to the case where the parties use N -1 device-independent quantum key distribution protocols in order to generate a common key. We show that for some regime of noise the DICKA protocol leads to better rates.

  18. Independent assessment for new nuclear reactor safety

    International Nuclear Information System (INIS)

    D'Auria, F.; Glaeser, H.; Debrecin, N.

    2017-01-01

    A rigorous framework for safety assessment is established in all countries where nuclear technology is used for the production of electricity. On one side, industry, i.e. reactor designers, vendors and utilities perform safety analysis and demonstrate consistency between results of safety analyses and requirements. On the other side, regulatory authorities perform independent assessment of safety and confirm the acceptability of safety of individual reactor units. The process of comparing results from analyses by reactor utilities and regulators is very complex. The process is also highly dependent upon mandatory approaches pursued for the analysis and from very many details which required the knowledge of sensitive proprietary data (e.g. spacer designs). Furthermore, all data available for the design, construction and operation of reactors produced by the nuclear industry are available to regulators. Two areas for improving the process of safety assessment for individual Nuclear Power Plant Units are identified: New details introduced by industry are not always and systematically requested by regulators for the independent assessment; New analytical techniques and capabilities are not necessarily used in the analyses by regulators (and by the industry). The established concept of independent assessment constitutes the way for improving the process of safety assessment. This is possible, or is largely facilitated, by the recent availability of the so-called Best Estimate Plus Uncertainty (BEPU) approach. (authors)

  19. Independent procedure of checking dose calculations using an independent calculus algorithm

    International Nuclear Information System (INIS)

    Perez Rozos, A.; Jerez Sainz, I.; Carrasco Rodriguez, J. L.

    2006-01-01

    In radiotherapy it is recommended the use of an independent procedure of checking dose calculations, in order to verify the main treatment planning system and double check every patient dosimetry. In this work we present and automatic spreadsheet that import data from planning system using IMPAC/RTP format and verify monitor unit calculation using an independent calculus algorithm. Additionally, it perform a personalized analysis of dose volume histograms and several radiobiological parameters like TCP and NTCP. Finally, the application automatically generate a clinical dosimetry report for every patient, including treatment fields, fractionation, independent check results, dose volume analysis, and first day forms. (Author)

  20. 48 CFR 731.773 - Independent research and development costs.

    Science.gov (United States)

    2010-10-01

    ... Organizations 731.773 Independent research and development costs. Pending establishment of Government-wide... independent research and development costs. ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Independent research and...

  1. Model-Independent and Quasi-Model-Independent Search for New Physics at CDF

    OpenAIRE

    CDF Collaboration

    2007-01-01

    Data collected in Run II of the Fermilab Tevatron are searched for indications of new electroweak scale physics. Rather than focusing on particular new physics scenarios, CDF data are analyzed for discrepancies with respect to the standard model prediction. A model-independent approach (Vista) considers the gross features of the data, and is sensitive to new large cross section physics. A quasi-model-independent approach (Sleuth) searches for a significant excess of events with large summed t...

  2. Executive dysfunction is independently associated with reduced functional independence in heart failure.

    Science.gov (United States)

    Alosco, Michael L; Spitznagel, Mary Beth; Raz, Naftali; Cohen, Ronald; Sweet, Lawrence H; Colbert, Lisa H; Josephson, Richard; van Dulmen, Manfred; Hughes, Joel; Rosneck, Jim; Gunstad, John

    2014-03-01

    To examine the independent association between executive function with instrumental activities of daily living and health behaviours in older adults with heart failure. Executive function is an important contributor to functional independence as it consists of cognitive processes needed for decision-making, planning, organising and behavioural monitoring. Impairment in this domain is common in heart failure patients and associated with reduced performance of instrumental activities of daily living in many medical and neurological populations. However, the contribution of executive functions to functional independence and healthy lifestyle choices in heart failure patients has not been fully examined. Cross-sectional analyses. One hundred and seventy-five heart failure patients completed a neuropsychological battery and echocardiogram. Participants also completed the Lawton-Brody Instrumental Activities of Daily Living Scale and reported current cigarette use. Hierarchical regressions revealed that reduced executive function was independently associated with worse instrumental activity of daily living performance with a specific association for decreased ability to manage medications. Partial correlations showed that executive dysfunction was associated with current cigarette use. Our findings suggest that executive dysfunction is associated with poorer functional independence and contributes to unhealthy behaviours in heart failure. Future studies should examine whether heart failure patients benefit from formal organisation schema (i.e. pill organisers) to maintain independence. Screening of executive function in heart failure patients may provide key insight into their ability to perform daily tasks, including the management of treatment recommendations. © 2013 John Wiley & Sons Ltd.

  3. Independence of Movement Preparation and Movement Initiation.

    Science.gov (United States)

    Haith, Adrian M; Pakpoor, Jina; Krakauer, John W

    2016-03-09

    Initiating a movement in response to a visual stimulus takes significantly longer than might be expected on the basis of neural transmission delays, but it is unclear why. In a visually guided reaching task, we forced human participants to move at lower-than-normal reaction times to test whether normal reaction times are strictly necessary for accurate movement. We found that participants were, in fact, capable of moving accurately ∼80 ms earlier than their reaction times would suggest. Reaction times thus include a seemingly unnecessary delay that accounts for approximately one-third of their duration. Close examination of participants' behavior in conventional reaction-time conditions revealed that they generated occasional, spontaneous errors in trials in which their reaction time was unusually short. The pattern of these errors could be well accounted for by a simple model in which the timing of movement initiation is independent of the timing of movement preparation. This independence provides an explanation for why reaction times are usually so sluggish: delaying the mean time of movement initiation relative to preparation reduces the risk that a movement will be initiated before it has been appropriately prepared. Our results suggest that preparation and initiation of movement are mechanistically independent and may have a distinct neural basis. The results also demonstrate that, even in strongly stimulus-driven tasks, presentation of a stimulus does not directly trigger a movement. Rather, the stimulus appears to trigger an internal decision whether to make a movement, reflecting a volitional rather than reactive mode of control. Copyright © 2016 the authors 0270-6474/16/363007-10$15.00/0.

  4. Independent accident investigation: a modern safety tool

    International Nuclear Information System (INIS)

    Stoop, John A.

    2004-01-01

    Historically, safety has been subjected to a fragmented approach. In the past, every department has had its own responsibility towards safety, focusing either on working conditions, internal safety, external safety, rescue and emergency, public order or security. They each issued policy documents, which in their time were leading statements for elaboration and regulation. They also addressed safety issues with tools of various nature, often specifically developed within their domain. Due to a series of major accidents and disasters, the focus of attention is shifting from complying with quantitative risk standards towards intervention in primary operational processes, coping with systemic deficiencies and a more integrated assessment of safety in its societal context. In The Netherlands recognition of the importance of independent investigations has led to an expansion of this philosophy from the transport sector to other sectors. The philosophy now covers transport, industry, defense, natural disaster, environment and health and other major occurrences such as explosions, fires, and collapse of buildings or structures. In 2003 a multi-sector covering law will establish an independent safety board in The Netherlands. At a European level, mandatory investigation agencies are recognized as indispensable safety instruments for aviation, railways and the maritime sector, for which EU Directives are in place or being progressed [Transport accident and incident investigation in the European Union, European Transport Safety Council, ISBN 90-76024-10-3, Brussel, 2001]. Due to a series of major events, attention has been drawn to the consequences of disasters, highlighting the involvement of rescue and emergency services. They also have become subjected to investigative efforts, which in return, puts demands on investigation methodology. This paper comments on an evolutionary development in safety thinking and of safety boards, highlighting some consequences for strategic

  5. Independent technical review of the Mound Plant

    Energy Technology Data Exchange (ETDEWEB)

    1994-06-01

    This report documents an Independent Technical Review (ITR) of the facilities, organizations, plans, and activities required to transition particular elements of the Mound Plant from Defense Program (DP) funded operation as appropriate either to community developed reuse or safe deactivation leading to decontamination and decommissioning (D&D). The review was conducted at the request of the Dr. Willis Bixby, Deputy Assistant Secretary, U.S. Department of Energy EM-60, Office of Facility Transition and Management and is a consensus of the nine member ITR Team. Information for the review was drawn from documents provided to the ITR Team by the Miamisburg Area Office (MB) of the DOE, EG&G, the City of Miamisburg, and others; and from presentations, discussions, interviews, and facility inspections at the Mound Plant during the weeks of March 14 and March 28, 1994. During the week of April 25, 1994, the ITR Team met at Los Alamos, New Mexico to develop consensus recommendations. A presentation of the core recommendations was made at the Mound Plant on May 5, 1994. This is an independent assessment of information available to, and used by, the Mound Plant personnel. Repetition of the information is not meant to imply discovery by the ITR Team. Team members, however, acting as independent reviewers, frequently assess the information from a perspective that differs significantly from that of the Mound Plant personnel. The report is based on information obtained and conditions observed during the March 1994 review interval. The ITR process and normal site work often initiate rapid, beneficial changes in understanding and organization immediately following the review. These changes frequently alter conditions observed during the review, but the report does not address changes subsequent to the review interval.

  6. Dimension-Independent Likelihood-Informed MCMC

    KAUST Repository

    Cui, Tiangang; Law, Kody; Marzouk, Youssef

    2015-01-01

    Many Bayesian inference problems require exploring the posterior distribution of high-dimensional parameters, which in principle can be described as functions. By exploiting low-dimensional structure in the change from prior to posterior [distributions], we introduce a suite of MCMC samplers that can adapt to the complex structure of the posterior distribution, yet are well-defined on function space. Posterior sampling in nonlinear inverse problems arising from various partial di erential equations and also a stochastic differential equation are used to demonstrate the e ciency of these dimension-independent likelihood-informed samplers.

  7. Morphology Independent Learning in Modular Robots

    DEFF Research Database (Denmark)

    Christensen, David Johan; Bordignon, Mirko; Schultz, Ulrik Pagh

    2009-01-01

    Hand-coding locomotion controllers for modular robots is difficult due to their polymorphic nature. Instead, we propose to use a simple and distributed reinforcement learning strategy. ATRON modules with identical controllers can be assembled in any configuration. To optimize the robot’s locomotion...... speed its modules independently and in parallel adjust their behavior based on a single global reward signal. In simulation, we study the learning strategy’s performance on different robot configurations. On the physical platform, we perform learning experiments with ATRON robots learning to move as fast...

  8. Information geometry near randomness and near independence

    CERN Document Server

    Arwini, Khadiga A

    2008-01-01

    This volume will be useful to practising scientists and students working in the application of statistical models to real materials or to processes with perturbations of a Poisson process, a uniform process, or a state of independence for a bivariate process. We use information geometry to provide a common differential geometric framework for a wide range of illustrative applications including amino acid sequence spacings in protein chains, cryptology studies, clustering of communications and galaxies, cosmological voids, coupled spatial statistics in stochastic fibre networks and stochastic porous media, quantum chaology. Introduction sections are provided to mathematical statistics, differential geometry and the information geometry of spaces of probability density functions.

  9. Pantex Falling Man - Independent Review Panel Report.

    Energy Technology Data Exchange (ETDEWEB)

    Brannon, Nathan Gregory; L. Bertolini, N. Brannon, J. Olsen, B. Price, M. Steinzig, R. Wardle, & M. Winfield

    2014-11-01

    Consolidated Nuclear Security (CNS) Pantex took the initiative to organize a Review Panel of subject matter experts to independently assess the adequacy of the Pantex Tripping Man Analysis methodology. The purpose of this report is to capture the details of the assessment including the scope, approach, results, and detailed Appendices. Along with the assessment of the analysis methodology, the panel evaluated the adequacy with which the methodology was applied as well as congruence with Department of Energy (DOE) standards 3009 and 3016. The approach included the review of relevant documentation, interactive discussion with Pantex staff, and the iterative process of evaluating critical lines of inquiry.

  10. Determinism, independence, and objectivity are incompatible.

    Science.gov (United States)

    Ionicioiu, Radu; Mann, Robert B; Terno, Daniel R

    2015-02-13

    Hidden-variable models aim to reproduce the results of quantum theory and to satisfy our classical intuition. Their refutation is usually based on deriving predictions that are different from those of quantum mechanics. Here instead we study the mutual compatibility of apparently reasonable classical assumptions. We analyze a version of the delayed-choice experiment which ostensibly combines determinism, independence of hidden variables on the conducted experiments, and wave-particle objectivity (the assertion that quantum systems are, at any moment, either particles or waves, but not both). These three ideas are incompatible with any theory, not only with quantum mechanics.

  11. Material-independent modes for electromagnetic scattering

    Science.gov (United States)

    Forestiere, Carlo; Miano, Giovanni

    2016-11-01

    In this Rapid Communication, we introduce a representation of the electromagnetic field for the analysis and synthesis of the full-wave scattering by a homogeneous dielectric object of arbitrary shape in terms of a set of eigenmodes independent of its permittivity. The expansion coefficients are rational functions of the permittivity. This approach naturally highlights the role of plasmonic and photonic modes in any scattering process and suggests a straightforward methodology to design the permittivity of the object to pursue a prescribed tailoring of the scattered field. We discuss in depth the application of the proposed approach to the analysis and design of the scattering properties of a dielectric sphere.

  12. Expertise and contra expertise independence and transparency

    International Nuclear Information System (INIS)

    Abarnou, G.; Ades, Y.; Ancelin, G.; Balle, St.; Bardy, J.Ch.; Beringer, F.; Blanc, M.; Bontoux, J.; Bovy, M.; Brunet, F.; Calafat, A.; Cartier, M.; Constant, H.; Delcourt, R.; Duvert, J.C.; Eichholtzer, F.; Fernandez, P.; Fernex, S.; Foechterle, A.; Gatesoupe, J.P.; Geneau, Ch.; Goerg, C.; Gourod, A.; Graschaire, G.; Hubscher Ibert, J.; Jaegert, M.; Lacoste, A.C.; Lacote, J.P.; Laroche, D.; Lazar, Ph.; Lelievre, D.; Levasseur, E.; Levent, L.; Louvat, D.; Manon, Ch.; Maugein, J.; Melguen, M.; Mouchet, Ch.; Mourat, J.P.; Naegelen, L.; Niquet, G.; Perves, J.P.; Potelet, P.; Regent, A.; Romann, J.M.; Rossa, N.; Saut, C.; Sazy, Ch.; Schmitt, P.; Sene, M.; Sene, Raymond; Sornein, J.F.; Sugier, A.; Tfibel, V.; Uhart, M.; Vidal, J.; Vieillard Baron, B.; Vigny, P.; Walgenwitz, G.; Wiest, A.; Wisselmann, R.; Zuberbuhler, A.

    2006-01-01

    About sixty participants: members of C.L.I., academics, elected representatives, manufacturers, representatives of association, institutional, crossed their experiences. The debate was mainly centred on the role of the expert, the limits of its intervention and its independence. The presented titles are following: experiences of two C.L.I. in expertise; the work of communication of the nuclear experts; interest and limits of the expertise; presentation of the I.R.S.N. and the D.G.S.N.R.; expertise: problems and experiences; presentation of the works realised in work group; the considerations of the C.S.S.I.N.. (N.C.)

  13. Dimension-Independent Likelihood-Informed MCMC

    KAUST Repository

    Cui, Tiangang

    2015-01-07

    Many Bayesian inference problems require exploring the posterior distribution of high-dimensional parameters, which in principle can be described as functions. By exploiting low-dimensional structure in the change from prior to posterior [distributions], we introduce a suite of MCMC samplers that can adapt to the complex structure of the posterior distribution, yet are well-defined on function space. Posterior sampling in nonlinear inverse problems arising from various partial di erential equations and also a stochastic differential equation are used to demonstrate the e ciency of these dimension-independent likelihood-informed samplers.

  14. Independent Component Analysis in Multimedia Modeling

    DEFF Research Database (Denmark)

    Larsen, Jan

    2003-01-01

    largely refers to text, images/video, audio and combinations of such data. We review a number of applications within single and combined media with the hope that this might provide inspiration for further research in this area. Finally, we provide a detailed presentation of our own recent work on modeling......Modeling of multimedia and multimodal data becomes increasingly important with the digitalization of the world. The objective of this paper is to demonstrate the potential of independent component analysis and blind sources separation methods for modeling and understanding of multimedia data, which...

  15. On conditional independence and log-convexity

    Czech Academy of Sciences Publication Activity Database

    Matúš, František

    2012-01-01

    Roč. 48, č. 4 (2012), s. 1137-1147 ISSN 0246-0203 R&D Projects: GA AV ČR IAA100750603; GA ČR GA201/08/0539 Institutional support: RVO:67985556 Keywords : Conditional independence * Markov properties * factorizable distributions * graphical Markov models * log-convexity * Gibbs- Markov equivalence * Markov fields * Gaussian distributions * positive definite matrices * covariance selection model Subject RIV: BA - General Mathematics Impact factor: 0.933, year: 2012 http://library.utia.cas.cz/separaty/2013/MTR/matus-0386229.pdf

  16. Experimental Measurement-Device-Independent Entanglement Detection

    Science.gov (United States)

    Nawareg, Mohamed; Muhammad, Sadiq; Amselem, Elias; Bourennane, Mohamed

    2015-02-01

    Entanglement is one of the most puzzling features of quantum theory and of great importance for the new field of quantum information. The determination whether a given state is entangled or not is one of the most challenging open problems of the field. Here we report on the experimental demonstration of measurement-device-independent (MDI) entanglement detection using witness method for general two qubits photon polarization systems. In the MDI settings, there is no requirement to assume perfect implementations or neither to trust the measurement devices. This experimental demonstration can be generalized for the investigation of properties of quantum systems and for the realization of cryptography and communication protocols.

  17. Enacting Risk in Independent Technological Innovation

    DEFF Research Database (Denmark)

    Berglund, Henrik; Hellström, Tomas

    2002-01-01

    The present study aims at investigating the role of risk in the activity of independent technological venturing. Altogether, 12 deep-interviews were conducted with technological entrepreneurs, who had taken part in the inventive, developmental and the commercialisation phases of a technology......-based innovation process. The interviews revealed a number of enactment approaches through which these innovators encountered and affected (dealt with or transformed) risk within the innovation process. Factors thus developed from the empirical material included human capital, pace and priority, the world moves...... for the benefit of innovation management....

  18. Fully Device-Independent Quantum Key Distribution

    Science.gov (United States)

    Vazirani, Umesh; Vidick, Thomas

    2014-10-01

    Quantum cryptography promises levels of security that are impossible to replicate in a classical world. Can this security be guaranteed even when the quantum devices on which the protocol relies are untrusted? This central question dates back to the early 1990s when the challenge of achieving device-independent quantum key distribution was first formulated. We answer this challenge by rigorously proving the device-independent security of a slight variant of Ekert's original entanglement-based protocol against the most general (coherent) attacks. The resulting protocol is robust: While assuming only that the devices can be modeled by the laws of quantum mechanics and are spatially isolated from each other and from any adversary's laboratory, it achieves a linear key rate and tolerates a constant noise rate in the devices. In particular, the devices may have quantum memory and share arbitrary quantum correlations with the eavesdropper. The proof of security is based on a new quantitative understanding of the monogamous nature of quantum correlations in the context of a multiparty protocol.

  19. Development of Independent-type Optical CT

    Science.gov (United States)

    Yamaguchi, Tatsushi; Shiozawa, Daigoro; Rokunohe, Toshiaki; Kida, Junzo; Zhang, Wei

    Optical current transformers (optical CTs) have features that they can be made much smaller and lighter than conventional electromagnetic induction transformers by their simple structure, and contribute to improvement of equipment reliability because of their excellent surge resistance performance. Authors consider optical CTs to be next generation transformers, and are conducting research and development of optical CTs aiming to apply to measuring and protection in electric power systems. Specifically we developed an independent-type optical CT by utilizing basic data of optical CTs accumulated for large current characteristics, temperature characteristics, vibration resistance characteristics, and so on. In performance verification, type tests complying with IEC standards, such as short-time current tests, insulation tests, accuracy tests, and so on, showed good results. This report describes basic principle and configuration of optical CTs. After that, as basic characteristics of optical CTs, conditions and results of verification tests for dielectric breakdown characteristics of sensor fibers, large current characteristics, temperature characteristics, and vibration resistance characteristics are described. Finally, development outline of the independent-type optical CT aiming to apply to all digital substation and its type tests results are described.

  20. Massively Parallel Dimension Independent Adaptive Metropolis

    KAUST Repository

    Chen, Yuxin

    2015-05-14

    This work considers black-box Bayesian inference over high-dimensional parameter spaces. The well-known and widely respected adaptive Metropolis (AM) algorithm is extended herein to asymptotically scale uniformly with respect to the underlying parameter dimension, by respecting the variance, for Gaussian targets. The result- ing algorithm, referred to as the dimension-independent adaptive Metropolis (DIAM) algorithm, also shows improved performance with respect to adaptive Metropolis on non-Gaussian targets. This algorithm is further improved, and the possibility of probing high-dimensional targets is enabled, via GPU-accelerated numerical libraries and periodically synchronized concurrent chains (justified a posteriori). Asymptoti- cally in dimension, this massively parallel dimension-independent adaptive Metropolis (MPDIAM) GPU implementation exhibits a factor of four improvement versus the CPU-based Intel MKL version alone, which is itself already a factor of three improve- ment versus the serial version. The scaling to multiple CPUs and GPUs exhibits a form of strong scaling in terms of the time necessary to reach a certain convergence criterion, through a combination of longer time per sample batch (weak scaling) and yet fewer necessary samples to convergence. This is illustrated by e ciently sampling from several Gaussian and non-Gaussian targets for dimension d 1000.

  1. Dimension-independent likelihood-informed MCMC

    KAUST Repository

    Cui, Tiangang

    2015-10-08

    Many Bayesian inference problems require exploring the posterior distribution of high-dimensional parameters that represent the discretization of an underlying function. This work introduces a family of Markov chain Monte Carlo (MCMC) samplers that can adapt to the particular structure of a posterior distribution over functions. Two distinct lines of research intersect in the methods developed here. First, we introduce a general class of operator-weighted proposal distributions that are well defined on function space, such that the performance of the resulting MCMC samplers is independent of the discretization of the function. Second, by exploiting local Hessian information and any associated low-dimensional structure in the change from prior to posterior distributions, we develop an inhomogeneous discretization scheme for the Langevin stochastic differential equation that yields operator-weighted proposals adapted to the non-Gaussian structure of the posterior. The resulting dimension-independent and likelihood-informed (DILI) MCMC samplers may be useful for a large class of high-dimensional problems where the target probability measure has a density with respect to a Gaussian reference measure. Two nonlinear inverse problems are used to demonstrate the efficiency of these DILI samplers: an elliptic PDE coefficient inverse problem and path reconstruction in a conditioned diffusion.

  2. Mid-space-independent deformable image registration.

    Science.gov (United States)

    Aganj, Iman; Iglesias, Juan Eugenio; Reuter, Martin; Sabuncu, Mert Rory; Fischl, Bruce

    2017-05-15

    Aligning images in a mid-space is a common approach to ensuring that deformable image registration is symmetric - that it does not depend on the arbitrary ordering of the input images. The results are, however, generally dependent on the mathematical definition of the mid-space. In particular, the set of possible solutions is typically restricted by the constraints that are enforced on the transformations to prevent the mid-space from drifting too far from the native image spaces. The use of an implicit atlas has been proposed as an approach to mid-space image registration. In this work, we show that when the atlas is aligned to each image in the native image space, the data term of implicit-atlas-based deformable registration is inherently independent of the mid-space. In addition, we show that the regularization term can be reformulated independently of the mid-space as well. We derive a new symmetric cost function that only depends on the transformation morphing the images to each other, rather than to the atlas. This eliminates the need for anti-drift constraints, thereby expanding the space of allowable deformations. We provide an implementation scheme for the proposed framework, and validate it through diffeomorphic registration experiments on brain magnetic resonance images. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Dimension-independent likelihood-informed MCMC

    KAUST Repository

    Cui, Tiangang; Law, Kody; Marzouk, Youssef M.

    2015-01-01

    Many Bayesian inference problems require exploring the posterior distribution of high-dimensional parameters that represent the discretization of an underlying function. This work introduces a family of Markov chain Monte Carlo (MCMC) samplers that can adapt to the particular structure of a posterior distribution over functions. Two distinct lines of research intersect in the methods developed here. First, we introduce a general class of operator-weighted proposal distributions that are well defined on function space, such that the performance of the resulting MCMC samplers is independent of the discretization of the function. Second, by exploiting local Hessian information and any associated low-dimensional structure in the change from prior to posterior distributions, we develop an inhomogeneous discretization scheme for the Langevin stochastic differential equation that yields operator-weighted proposals adapted to the non-Gaussian structure of the posterior. The resulting dimension-independent and likelihood-informed (DILI) MCMC samplers may be useful for a large class of high-dimensional problems where the target probability measure has a density with respect to a Gaussian reference measure. Two nonlinear inverse problems are used to demonstrate the efficiency of these DILI samplers: an elliptic PDE coefficient inverse problem and path reconstruction in a conditioned diffusion.

  4. Viewpoint-independent contextual cueing effect

    Directory of Open Access Journals (Sweden)

    taiga etsuchiai

    2012-06-01

    Full Text Available We usually perceive things in our surroundings as unchanged despite viewpoint changes caused by self-motion. The visual system therefore must have a function to process objects independently of viewpoint. In this study, we examined whether viewpoint-independent spatial layout can be obtained implicitly. For this purpose, we used a contextual cueing effect, a learning effect of spatial layout in visual search displays known to be an implicit effect. We compared the transfer of the contextual cueing effect between cases with and without self-motion by using visual search displays for 3D objects, which changed according to the participant’s assumed location for viewing the stimuli. The contextual cueing effect was obtained with self-motion but disappeared when the display changed without self-motion. This indicates that there is an implicit learning effect in spatial coordinates and suggests that the spatial representation of object layouts or scenes can be obtained and updated implicitly. We also showed that binocular disparity play an important role in the layout representations.

  5. Measurement-device-independent quantum digital signatures

    Science.gov (United States)

    Puthoor, Ittoop Vergheese; Amiri, Ryan; Wallden, Petros; Curty, Marcos; Andersson, Erika

    2016-08-01

    Digital signatures play an important role in software distribution, modern communication, and financial transactions, where it is important to detect forgery and tampering. Signatures are a cryptographic technique for validating the authenticity and integrity of messages, software, or digital documents. The security of currently used classical schemes relies on computational assumptions. Quantum digital signatures (QDS), on the other hand, provide information-theoretic security based on the laws of quantum physics. Recent work on QDS Amiri et al., Phys. Rev. A 93, 032325 (2016);, 10.1103/PhysRevA.93.032325 Yin, Fu, and Zeng-Bing, Phys. Rev. A 93, 032316 (2016), 10.1103/PhysRevA.93.032316 shows that such schemes do not require trusted quantum channels and are unconditionally secure against general coherent attacks. However, in practical QDS, just as in quantum key distribution (QKD), the detectors can be subjected to side-channel attacks, which can make the actual implementations insecure. Motivated by the idea of measurement-device-independent quantum key distribution (MDI-QKD), we present a measurement-device-independent QDS (MDI-QDS) scheme, which is secure against all detector side-channel attacks. Based on the rapid development of practical MDI-QKD, our MDI-QDS protocol could also be experimentally implemented, since it requires a similar experimental setup.

  6. Vietnamese women in struggle for national independence.

    Science.gov (United States)

    1998-01-01

    The 30-year struggle for independence in Viet Nam took a huge toll on women, but even in the hardest times, Vietnamese women received support from the world-wide women's movement. As the world prepares to enter the new millennium, it is important to determine what policies can be created to prevent war and guarantee peace. These policies must grow out of international agreement on basic principles such as respect for independence and sovereignty and must not resort to the embargoes and sanctions that have placed a disproportionate burden on women and children. Another challenge of the new millennium is to encourage implementation of national programs, policies, and measures to help women realize their rights while preserving traditional family values. Despite the heightened visibility of the international women's movement, women still suffer from widespread inequalities. In accordance with the goals of the Communist Party of Viet Nam, the 8th Congress of Vietnamese Women in 1997 created a national plan for women that is a blueprint for the women's movement for the years 1997-2000. Among the goals are creating jobs for women, upgrading their standard of living, eliminating hunger, decreasing poverty, and ensuring that women have educational opportunities. Vietnamese women also seek to strengthen their relationship with other women in the international community, and the Vietnamese Women's Union has actively forwarded the objectives of the Federation of International Democratic Women.

  7. OSART Independent Safety Culture Assessment (ISCA) Guidelines

    International Nuclear Information System (INIS)

    2016-01-01

    Safety culture is understood as an important part of nuclear safety performance. This has been demonstrated by the analysis of significant events such as Chernobyl, Davis Besse, Vandellos II, Asco, Paks, Mihamma and Forsmark, among others. In order to enhance safety culture, one essential activity is to perform assessments. IAEA Safety Standard Series No. GS-R-3, The Management System for Facilitites and Activities, states requirements for continuous improvement of safety culture, of which self, peer and independent safety culture assessments constitute an essential part. In line with this requirement, the Independent Safety Culture Assessment (ISCA) module is offered as an add-on module to the IAEA Operational Safety Review Team (OSART) programme. The OSART programme provides advice and assistance to Member States to enhance the safety of nuclear power plants during commissioning and operation. By including the ISCA module in an OSART mission, the receiving organization benefits from the synergy between the technical and the safety culture aspects of the safety review. The joint operational safety and safety culture assessment provides the organization with the opportunity to better understand the interactions between technical, human, organizational and cultural aspects, helping the organization to take a systemic approach to safety through identifying actions that fully address the root causes of any identified issue. Safety culture assessments provide insight into the fundamental drivers that shape organizational patterns of behaviour, safety consciousness and safety performance. The complex nature of safety culture means that the analysis of the results of such assessments is not as straightforward as for other types of assessment. The benefits of the results of nuclear safety culture assessments are maximized only if appropriate tools and guidance for these assessments is used; hence, this comprehensive guideline has been developed. The methodology explained

  8. Partitioning a macroscopic system into independent subsystems

    Science.gov (United States)

    Delle Site, Luigi; Ciccotti, Giovanni; Hartmann, Carsten

    2017-08-01

    We discuss the problem of partitioning a macroscopic system into a collection of independent subsystems. The partitioning of a system into replica-like subsystems is nowadays a subject of major interest in several fields of theoretical and applied physics. The thermodynamic approach currently favoured by practitioners is based on a phenomenological definition of an interface energy associated with the partition, due to a lack of easily computable expressions for a microscopic (i.e. particle-based) interface energy. In this article, we outline a general approach to derive sharp and computable bounds for the interface free energy in terms of microscopic statistical quantities. We discuss potential applications in nanothermodynamics and outline possible future directions.

  9. Turkish Independence War and its consequences

    Directory of Open Access Journals (Sweden)

    Alexandru‑Nicolae Cucu

    2014-11-01

    Full Text Available At the end of the First World War, the Ottoman Empire collapsed and the Great Powers came to take the control of its territories. Having a strategic position at the southern gate of Europe, all of Turkish lands were very important for the First World War winners, both to secure European borders and to develop the trade between Europe and Middle East. On the other side, under Mustafa Kemal Atatürk command, a new Turkey with a strong nationalist way decided to fight for emancipating. Winning the war with the Great Powers not only in a military way, but also from a diplomatic perspective, the new Turkey became a modern regional power, having institutions and laws that assured its prosperity and security. Taking into consideration the independence war evolution, this paper wants also to show the diplomatic capability of Turkish leaders to balance between powers involved in the region.

  10. Process-independent strong running coupling

    International Nuclear Information System (INIS)

    Binosi, Daniele; Mezrag, Cedric; Papavassiliou, Joannis; Roberts, Craig D.; Rodriguez-Quintero, Jose

    2017-01-01

    Here, we unify two widely different approaches to understanding the infrared behavior of quantum chromodynamics (QCD), one essentially phenomenological, based on data, and the other computational, realized via quantum field equations in the continuum theory. Using the latter, we explain and calculate a process-independent running-coupling for QCD, a new type of effective charge that is an analogue of the Gell-Mann–Low effective coupling in quantum electrodynamics. The result is almost identical to the process-dependent effective charge defined via the Bjorken sum rule, which provides one of the most basic constraints on our knowledge of nucleon spin structure. As a result, this reveals the Bjorken sum to be a near direct means by which to gain empirical insight into QCD's Gell-Mann–Low effective charge.

  11. Risk allocation in independent power supply contracts

    International Nuclear Information System (INIS)

    Willrich, M.; Campbell, W.L.

    1992-01-01

    Congress has made significant progress in recent months toward amending the Public Utility Holding Company Act of 1935 (PUHCA). The purposes of such amendment are to broaden power supply options for electric utilities and expand competition in whole-sale power generation markets. PUHCA reform is an integral part of President Bush's National Energy Strategy and has been included in legislation pending in both Houses of Congress. Congress will, hopefully, approve energy legislation that includes PUHCA reform before it adjourns this year. PUHCA reform has, however, stimulated heated debate within the power industry itself as well as among various consumer interest groups. One important issue in the public debate concerns risk allocation. If PUHCA is reformed, will risk be allocated efficiently and equitably between independent power producers and electric utility buyers? This article addresses that important question

  12. Emotional responses as independent components in EEG

    DEFF Research Database (Denmark)

    Jensen, Camilla Birgitte Falk; Petersen, Michael Kai; Larsen, Jakob Eg

    2014-01-01

    susceptible to noise if captured in a mobile context. Hypothesizing that retrieval of emotional responses in mobile usage scenarios could be enhanced through spatial filtering, we compare a standard EEG electrode based analysis against an approach based on independent component analysis (ICA). By clustering...... or unpleasant images; early posterior negativity (EPN) and late positive potential (LPP). Recent studies suggest that several time course components may be modulated by emotional content in images or text. However these neural signatures are characterized by small voltage changes that would be highly...... by emotional content. We propose that similar approaches to spatial filtering might allow us to retrieve more robust signals in real life mobile usage scenarios, and potentially facilitate design of cognitive interfaces that adapt the selection of media to our emotional responses....

  13. Independent System Calibration of Sentinel-1B

    Directory of Open Access Journals (Sweden)

    Marco Schwerdt

    2017-05-01

    Full Text Available Sentinel-1B is the second of two C-Band Synthetic Aperture Radar (SAR satellites of the Sentinel-1 mission, launched in April 2016—two years after the launch of the first satellite, Sentinel-1A. In addition to the commissioning of Sentinel-1B executed by the European Space Agency (ESA, an independent system calibration was performed by the German Aerospace Center (DLR on behalf of ESA. Based on an efficient calibration strategy and the different calibration procedures already developed and applied for Sentinel-1A, extensive measurement campaigns were executed by initializing and aligning DLR’s reference targets deployed on the ground. This paper describes the different activities performed by DLR during the Sentinel-1B commissioning phase and presents the results derived from the analysis and the evaluation of a multitude of data takes and measurements.

  14. Distributed-Memory Fast Maximal Independent Set

    Energy Technology Data Exchange (ETDEWEB)

    Kanewala Appuhamilage, Thejaka Amila J.; Zalewski, Marcin J.; Lumsdaine, Andrew

    2017-09-13

    The Maximal Independent Set (MIS) graph problem arises in many applications such as computer vision, information theory, molecular biology, and process scheduling. The growing scale of MIS problems suggests the use of distributed-memory hardware as a cost-effective approach to providing necessary compute and memory resources. Luby proposed four randomized algorithms to solve the MIS problem. All those algorithms are designed focusing on shared-memory machines and are analyzed using the PRAM model. These algorithms do not have direct efficient distributed-memory implementations. In this paper, we extend two of Luby’s seminal MIS algorithms, “Luby(A)” and “Luby(B),” to distributed-memory execution, and we evaluate their performance. We compare our results with the “Filtered MIS” implementation in the Combinatorial BLAS library for two types of synthetic graph inputs.

  15. ON INTERSECTIONS OF INDEPENDENT NONDEGENERATE DIFFUSION PROCESSES

    Institute of Scientific and Technical Information of China (English)

    Zhenlong CHEN

    2014-01-01

    Let X(1) = {X(1)(s), s ∈ R+} and X(2) = {X(2)(t), t ∈ R+} be two inde-pendent nondegenerate diffusion processes with values in Rd. The existence and fractal dimension of intersections of the sample paths of X (1) and X (2) are studied. More gener-ally, let E1, E2⊆(0,∞) and F ⊂Rd be Borel sets. A necessary condition and a suffcient condition for P{X(1)(E1)∩X(2)(E2)∩F 6=∅}>0 are proved in terms of the Bessel-Riesz type capacity and Hausdorff measure of E1 × E2 × F in the metric space (R+× R+× Rd,ρb), whereρb is an unsymmetric metric defined in R+× R+× Rd. Under reasonable conditions, results resembling those of Browian motion are obtained.

  16. Independent Navigation System for a Surgical Colonoscope

    Directory of Open Access Journals (Sweden)

    Lilia A. Ochoa-Luna

    2013-08-01

    Full Text Available This paper provides a novel algorithm to attain the independent navigation of a colonoscopy surgical endoscope. First, it introduces a brief description of this issue through the scientist advance for medical robotics. It then makes a quickly count of the existent methods and at the end it provides the basis in order to propose a new alternative solution with help from vision-guidance. That means that images will be processed and interpreted with the purpose of maintaining the endoscope always at the intestine center. All this considered will help us to reduce colonoscopy surgeries consequences and the most important advantage of this new method proposed is that surgeons will accomplish their work easier and more efficiently.

  17. Stable Chimeras and Independently Synchronizable Clusters

    Science.gov (United States)

    Cho, Young Sul; Nishikawa, Takashi; Motter, Adilson E.

    2017-08-01

    Cluster synchronization is a phenomenon in which a network self-organizes into a pattern of synchronized sets. It has been shown that diverse patterns of stable cluster synchronization can be captured by symmetries of the network. Here, we establish a theoretical basis to divide an arbitrary pattern of symmetry clusters into independently synchronizable cluster sets, in which the synchronization stability of the individual clusters in each set is decoupled from that in all the other sets. Using this framework, we suggest a new approach to find permanently stable chimera states by capturing two or more symmetry clusters—at least one stable and one unstable—that compose the entire fully symmetric network.

  18. Publications in Cuba after Latin American Independences

    Directory of Open Access Journals (Sweden)

    Juan José SÁNCHEZ BAENA

    2011-04-01

    Full Text Available This article has a double objective. On the one hand, it aims to offer a vision of the consequences of the liberal Triennium, and the end of Spanish domain in continental America, on the Cuban printing culture. On the other hand, it analyses the main aspects that influenced Cuban society through the most important periodical contents. The extraordinary economic and commercial development, whose most influential agent was the economic group denominated «sacarocracia», made the printing evolution unstoppable, despite the strong control and censorship imposed by the Spanish government fearing the independence of near Republics. Some new serial publications with good content appeared, such as Revista Bimestre Cubana, and the expansion of printing slowly began in new Cuban populations.

  19. Blockbuster genres in Danish independent film

    DEFF Research Database (Denmark)

    Hansen, Kim Toft

    2013-01-01

    is a certain reluctance towards supporting specific international blockbuster genres such as horror, the gangster drama and action film. Throughout the past decade, Danish independent cinema – motivated by for instance the alternative film school Super16 and self-governing film-milieus around Denmark – has...... genres and styles in the search for what is missing in Danish cinema. This works for some directors, principally, by directly reacting against the institutional and economic dominance and protectionism of primarily The Danish Film Institute. Indirectly, the some of the filmmakers seem to react against...... ‘what is allowed’ in Danish film culture. Thus, they actually define themselves as being non-mainstream by focussing on international mainstream genres. By way of examples from the Danish indie scene and interviews with noteworthy indie filmmakers, this article draws attention to a still fairly...

  20. Angle-independent structural colors of silicon

    DEFF Research Database (Denmark)

    Højlund-Nielsen, Emil; Weirich, Johannes; Nørregaard, Jesper

    2014-01-01

    Structural colors are optical phenomena of physical origin, where microscale and nanoscale structures determine the reflected spectrum of light. Artificial structural colors have been realized within recent years. However, multilayer structures require substantial fabrication. Instead we considered...... one-layer surface textures of silicon.We explored four patterns of square structures in a square lattice with periods of 500, 400, 300, and 200 nm. The reflectivity and daylight-colors were measured and compared with simulations based on rigorously coupledwave analysis with excellent agreement. Based...... on the 200-nm periodic pattern, it was found that angle-independent specular colors up to 60 deg of incidence may be provided. The underlying mechanisms include (1) the suppression of diffraction and (2) a strong coupling of light to localized surface states. The strong coupling yields absorption anomalies...

  1. The Faroe Islands: Options for Independence

    Directory of Open Access Journals (Sweden)

    Maria Ackren

    2006-11-01

    Full Text Available The Faroe Islands are currently at a crossroads in their constitutional status. Discussions concerning changes in the current constitutional status are ongoing and several analyses about possible trajectories of future development are being proposed. Argued in a context of Faroese nationalism, this article tries to assess these trajectories in the future jurisdictional and political development of the Faroe Islands in terms of three possible scenarios: independence or full sovereignty (as is Iceland; a freely associated statehood (as are Niue and the Cook Islands in relation to New Zealand; or a confederation, probably involving changes at both the central level of the Danish state and the European Union level. This article argues that the most likely future development is that of a state in free association with Denmark. Meanwhile, island politics can change very quickly and the traditional cleavages in Faroese politics are liable to changing degrees of public support.

  2. Yield stress independent column buckling curves

    DEFF Research Database (Denmark)

    Stan, Tudor‐Cristian; Jönsson, Jeppe

    2017-01-01

    of the yield stress is to some inadequate degree taken into account in the Eurocode by specifying that steel grades of S460 and higher all belong to a common set of “raised” buckling curves. This is not satisfying as it can be shown theoretically that the current Eurocode formulation misses an epsilon factor......Using GMNIA and shell finite element modelling of steel columns it is ascertained that the buckling curves for given imperfections and residual stresses are not only dependent on the relative slenderness ratio and the cross section shape but also on the magnitude of the yield stress. The influence...... in the definition of the normalised imperfection magnitudes. By introducing this factor it seems that the GMNIA analysis and knowledge of the independency of residual stress levels on the yield stress can be brought together and give results showing consistency between numerical modelling and a simple modified...

  3. Cognitive independence in foreign language learning

    Directory of Open Access Journals (Sweden)

    Maylín Rodríguez Sánchez

    2015-09-01

    Full Text Available The paper is intended to describe a didactic strategy to contribute to the development of foreign languages course students’ cognitive independence at Camagüey University. In its theoretical conception it is re-defined the concept “cognitive independence”, springing from the context in which the research is carried out, and the distinguishing features that characterize this capacity in students of foreign languages for pedagogical purposes are determined. The strategy comprises four stages: diagnosis, planning, execution, and evaluation. It is included the exemplification of the actions comprised in each stage, as well as the valuation of its effectiveness by means of experts’ opinions. Theoretical and empirical methods were applied, allowing the identification of the scientific problem and the modeling of its solution.

  4. Deafblind people, communication, independence, and isolation.

    Science.gov (United States)

    Hersh, Marion

    2013-10-01

    This paper discusses issues related to communication, independence, and isolation for an understudied group of deaf people who also have visual impairments. The discussion is based on the experiences of 28 deafblind people in 6 different countries, obtained from interviews that were carried out as part of a larger research project on travel issues. However, the similarities in experiences between countries were stronger than the differences. In particular, barriers to communication and inadequate support, with resulting problems of isolation and depression, were found in all the countries. Equally, deafblind people in all the countries were interested in being involved in and contributing to society and supporting other people, particularly through organizations of blind and deafblind people. This runs counter to the tendency to present deafblind and other disabled people purely as recipients of support rather than also as active participants in society. However, there were some differences in the support available in the different countries.

  5. Independent isomer yield ratio of 90Rb

    International Nuclear Information System (INIS)

    Reeder, P.L.; Warner, R.A.; Ford, G.P.; Willmes, H.

    1985-05-01

    The independent isomer yield ratio for 90 Rb from thermal neutron fission of 235 U has been measured by use of a new technique involving a pulsed reactor and an on-line mass spectrometer facility. The apparent isomer yield ratio was measured for different ion collection time intervals and extrapolated to zero collection time to eliminate interference from 90 Kr decay. The observed isomer yield ratio of 8.7 +- 1.0 is one of the largest ratios measured for a low energy fission process. However, a statistical model analysis shows that the average angular momentum ( = 4.5) deduced from this isomer yield ratio is consistent with average angular momentum for other products from low energy fission. 7 refs

  6. Parkin suppresses Drp1-independent mitochondrial division

    International Nuclear Information System (INIS)

    Roy, Madhuparna; Itoh, Kie; Iijima, Miho; Sesaki, Hiromi

    2016-01-01

    The cycle of mitochondrial division and fusion disconnect and reconnect individual mitochondria in cells to remodel this energy-producing organelle. Although dynamin-related protein 1 (Drp1) plays a major role in mitochondrial division in cells, a reduced level of mitochondrial division still persists even in the absence of Drp1. It is unknown how much Drp1-mediated mitochondrial division accounts for the connectivity of mitochondria. The role of a Parkinson’s disease-associated protein—parkin, which biochemically and genetically interacts with Drp1—in mitochondrial connectivity also remains poorly understood. Here, we quantified the number and connectivity of mitochondria using mitochondria-targeted photoactivatable GFP in cells. We show that the loss of Drp1 increases the connectivity of mitochondria by 15-fold in mouse embryonic fibroblasts (MEFs). While a single loss of parkin does not affect the connectivity of mitochondria, the connectivity of mitochondria significantly decreased compared with a single loss of Drp1 when parkin was lost in the absence of Drp1. Furthermore, the loss of parkin decreased the frequency of depolarization of the mitochondrial inner membrane that is caused by increased mitochondrial connectivity in Drp1-knockout MEFs. Therefore, our data suggest that parkin negatively regulates Drp1-indendent mitochondrial division. -- Highlights: •A Drp1-mediated mechanism accounts for ∼95% of mitochondrial division. •Parkin controls the connectivity of mitochondria via a mechanism that is independent of Drp1. •In the absence of Drp1, connected mitochondria transiently depolarize. •The transient depolarization is independent of calcium signaling and uncoupling protein 2.

  7. Parkin suppresses Drp1-independent mitochondrial division

    Energy Technology Data Exchange (ETDEWEB)

    Roy, Madhuparna, E-mail: mroy17@jhmi.edu; Itoh, Kie, E-mail: kito5@jhmi.edu; Iijima, Miho, E-mail: miijima@jhmi.edu; Sesaki, Hiromi, E-mail: hsesaki@jhmi.edu

    2016-07-01

    The cycle of mitochondrial division and fusion disconnect and reconnect individual mitochondria in cells to remodel this energy-producing organelle. Although dynamin-related protein 1 (Drp1) plays a major role in mitochondrial division in cells, a reduced level of mitochondrial division still persists even in the absence of Drp1. It is unknown how much Drp1-mediated mitochondrial division accounts for the connectivity of mitochondria. The role of a Parkinson’s disease-associated protein—parkin, which biochemically and genetically interacts with Drp1—in mitochondrial connectivity also remains poorly understood. Here, we quantified the number and connectivity of mitochondria using mitochondria-targeted photoactivatable GFP in cells. We show that the loss of Drp1 increases the connectivity of mitochondria by 15-fold in mouse embryonic fibroblasts (MEFs). While a single loss of parkin does not affect the connectivity of mitochondria, the connectivity of mitochondria significantly decreased compared with a single loss of Drp1 when parkin was lost in the absence of Drp1. Furthermore, the loss of parkin decreased the frequency of depolarization of the mitochondrial inner membrane that is caused by increased mitochondrial connectivity in Drp1-knockout MEFs. Therefore, our data suggest that parkin negatively regulates Drp1-indendent mitochondrial division. -- Highlights: •A Drp1-mediated mechanism accounts for ∼95% of mitochondrial division. •Parkin controls the connectivity of mitochondria via a mechanism that is independent of Drp1. •In the absence of Drp1, connected mitochondria transiently depolarize. •The transient depolarization is independent of calcium signaling and uncoupling protein 2.

  8. Model-independent particle accelerator tuning

    Directory of Open Access Journals (Sweden)

    Alexander Scheinker

    2013-10-01

    Full Text Available We present a new model-independent dynamic feedback technique, rotation rate tuning, for automatically and simultaneously tuning coupled components of uncertain, complex systems. The main advantages of the method are: (1 it has the ability to handle unknown, time-varying systems, (2 it gives known bounds on parameter update rates, (3 we give an analytic proof of its convergence and its stability, and (4 it has a simple digital implementation through a control system such as the experimental physics and industrial control system (EPICS. Because this technique is model independent it may be useful as a real-time, in-hardware, feedback-based optimization scheme for uncertain and time-varying systems. In particular, it is robust enough to handle uncertainty due to coupling, thermal cycling, misalignments, and manufacturing imperfections. As a result, it may be used as a fine-tuning supplement for existing accelerator tuning/control schemes. We present multiparticle simulation results demonstrating the scheme’s ability to simultaneously adaptively adjust the set points of 22 quadrupole magnets and two rf buncher cavities in the Los Alamos Neutron Science Center (LANSCE Linear Accelerator’s transport region, while the beam properties and rf phase shift are continuously varying. The tuning is based only on beam current readings, without knowledge of particle dynamics. We also present an outline of how to implement this general scheme in software for optimization, and in hardware for feedback-based control/tuning, for a wide range of systems.

  9. Water as an Independent Taste Modality

    Directory of Open Access Journals (Sweden)

    Andrew M Rosen

    2010-10-01

    Full Text Available To qualify as a basic taste quality or modality, defined as a group of chemicals that taste alike, three empirical benchmarks have commonly been used. The first is that a candidate group of tastants must have a dedicated transduction mechanism in the peripheral nervous system. The second is that the tastants evoke physiological responses in dedicated afferent taste nerves innervating the oropharyngeal cavity. Last, the taste stimuli evoke activity in central gustatory neurons, some of which may respond only to that group of tastants. Here we argue that water may also be an independent taste modality. This argument is based on the identification of a water dedicated transduction mechanism in the peripheral nervous system, water responsive fibers of the peripheral taste nerves and the observation of water responsive neurons in all gustatory regions within the central nervous system. We have described electrophysiological responses from single neurons in nucleus of the solitary tract (NTS and parabrachial nucleus of the pons (PbN, respectively the first two central relay nuclei in the rodent brainstem, to water presented as a taste stimulus in anesthetized rats. Responses to water were in some cases as robust as responses to other taste qualities and sometimes occurred in the absence of responses to other tastants. Both excitatory and inhibitory responses were observed. Also, the temporal features of the water response resembled those of other taste responses. We argue that water may constitute an independent taste modality that is processed by dedicated neural channels at all levels of the gustatory neuraxis. Water-dedicated neurons in the brainstem may constitute key elements in the regulatory system for fluid in the body, i.e. thirst, and as part of the swallowing reflex circuitry.

  10. The gauge-independent QCD effective charge

    International Nuclear Information System (INIS)

    Watson, N.J.

    1997-01-01

    It is shown how the QED concept of a gauge-, scale- and scheme-independent one-loop effective charge can be extended directly at the diagrammatic level to QCD, thus justifying explicitly the ''naive non-abelianization'' prescription used in renormalon calculus. It is first argued that, for on-shell external fields and at the strictly one-loop level, the required gluon self-energy-like function is precisely that obtained from S-matrix elements via the pinch technique. The generalization of the pinch technique to explicitly off-shell processes is then introduced. It is shown how, as a result of a fundamental cancellation among conventional perturbation theory diagrams, encoded in the QCD Ward identities, the pinch technique one-loop gluon self-energy iΠ μν ab (q) remains gauge-independent and universal regardless of the fact that the ''external'' fields in the given process are off-shell. This demonstration involves a simple technique enabling the isolation, in an arbitrary gauge, of iΠ μν ab (q) from subclasses of up to several hundred diagrams at once. Furthermore, it is shown how this one-loop cancellation mechanism iterates for the subclasses of n-loop diagrams containing implicitly the Dyson chains of n one-loop self-energies iΠ μν ab (q). The gauge cancellation required for the Dyson summation of iΠ μν ab (q) is thus demonstrated explicitly in a general class of ghost-free gauges for all orders n. (orig.)

  11. The gauge-independent QCD effective charge

    International Nuclear Information System (INIS)

    Watson, N.J.

    1999-01-01

    It is shown how the QCD concept of a gauge-, scale-and scheme-independent one-loop effective charge can be extended directly at the diagrammatic level to QCD, thus justifying explicitly the 'naive non-abelialization' prescription used in renormalon calculus. It is first argued that, for one-shell external fields and at the strictly one-loop level, the required gluon self-energy-like function is precisely that obtained from S-matrix elements via the pinch technique. The generalization of the pinch technique to explicitly off-shell processes is then introduced. It is shown how, as a result of a fundamental cancellation among conventional perturbation theory diagrams encoded in the QCD Ward identities, the pinch technique one-loop gluon self-energy iΠ μν ab (q) remains gauge-independent and universal regardless of the fact that the 'external' fields in the given process are off-shell. This demonstration involves a simple technique enabling the isolation in a arbitrary gauge, of iΠ μν ab (q) from subclasses of up to several hundreds diagrams at once. Furthermore, it is shown how this one-loop cancellation mechanism iterates for the subclasses of n-loop diagrams containing implicitly the Dyson chains of n-loop self energies iΠ μν ab (q). The gauge cancellation required for the Dyson summation of iΠ μν ab (q) is thus demonstrated explicitly in the class of ghost-free gauges for all orders n. (authors)

  12. Reference-Frame-Independent and Measurement-Device-Independent Quantum Key Distribution Using One Single Source

    Science.gov (United States)

    Li, Qian; Zhu, Changhua; Ma, Shuquan; Wei, Kejin; Pei, Changxing

    2018-04-01

    Measurement-device-independent quantum key distribution (MDI-QKD) is immune to all detector side-channel attacks. However, practical implementations of MDI-QKD, which require two-photon interferences from separated independent single-photon sources and a nontrivial reference alignment procedure, are still challenging with current technologies. Here, we propose a scheme that significantly reduces the experimental complexity of two-photon interferences and eliminates reference frame alignment by the combination of plug-and-play and reference frame independent MDI-QKD. Simulation results show that the secure communication distance can be up to 219 km in the finite-data case and the scheme has good potential for practical MDI-QKD systems.

  13. Independence and the Irish Environmental Protection Agency: A Comparative Assessment

    OpenAIRE

    Shipan, Charles

    2006-01-01

    The Environmental Protection Agency is one of the most prominent regulatory agencies in Ireland. Created in 1992, one of the hallmarks of this agency is its independence from other parts of government. Yet little is known about the actual extent of its independence. Independence and the Irish Environmental Protection Agency: A Comparative Assessment addresses several key questions about the agency's independence. Why was independence such a primary justification for the creation of this a...

  14. The Independence Pipeline project : ANR's supply link - Independence Pipeline, Transco's market link

    International Nuclear Information System (INIS)

    Persells, T.

    1998-01-01

    An overview of the Independence Pipeline project was presented. The project offers access from Chicago to the U.S. Midwest market, as well as to Ontario via MichCon, Consumers Power, Great Lakes and Panhandle. The project has three components: ANR's Supply Link, the Independence Pipeline and Transco's MarketLink. The three components are budgeted at $ 1.332 billion dollars and projected for completion between Nov 1999 and Nov 2000. Each component (services, access advantages, market links, rates, storage services, etc ) are described separately. figs

  15. Antargaz: 1. independent French LPG marketer; Antargaz: 1. destributeur francais independant de GPL

    Energy Technology Data Exchange (ETDEWEB)

    Anon.

    2001-04-01

    Francois Varagne, recently appointed President and General Manager of Antargaz, displayed on 12 April in Paris the configuration and the ambitions of the company. A major player on the French LPG market, Antargaz makes today a new start. On the basis of its 744 000 tonnes (around 400 millions gallons) sold in 2000, Antargaz ranks as the second LPG distributor in France with a share of some 24%. Antargaz is now the first independent marketer in France, ahead of the other French independent actors: Primagaz France (around 20% of the market) and Vitogaz (some 3.5%). Thus, key factors changed in the French LPG sector. If we except marketers under 5%, there were last year one large independent (Primagaz) and three LPG marketers linked to refiners: Butagaz (as Shell affiliate + BP's French LPG output), Elf Antargaz (as Elf Aquitaine's affiliate) and Totalgaz (as TotalFina's affiliate). Today, again without counting marketers under 5%, there are two LPG marketers linked to refiners (Butagaz and Totalgaz) and two large independents. Antargaz's strategy is focused on existing markets as well as new ones and new applications: in the domestic and commercial sectors, in industry, auto-gas, mains distribution, in the leisure sector, in agriculture. It has also a role to play in Europe.

  16. Supplying safety and energy independence; Securite d'approvisionnement et independance energetique

    Energy Technology Data Exchange (ETDEWEB)

    Maillard, D. [Ministere de l' Economie, des Finances et de l' Industrie, 75 - Paris (France). Direction Generale de L' Energie et des Matieres Premieres

    2001-03-01

    The french Observatory of the Energy wonders about the energy independence notion. Many risks are possible: physical, economical, geo-political, social and ecological risks. Because those risks are numerous, the answers for a supplying safety are also numerous. In this context the energy policy is a difficult art which the public opinion needs to be more and more aware. (A.L.B.)

  17. TARGETED TECHNOLOGY TRANSFER TO US INDEPENDENTS

    Energy Technology Data Exchange (ETDEWEB)

    Donald F. Duttlinger; E. Lance Cole

    2005-01-01

    The Petroleum Technology Transfer Council (PTTC) continued pursuing its mission of assisting U.S. independent oil and gas producers with timely, informed technology decisions during Fiscal Year 2004 (FY04). PTTC has active grassroots programs through its 10 Regional Lead Organizations (RLOs) and 2 satellite offices. They bring research and academia to the table via their association with geological surveys and engineering departments. The regional directors interact with independent oil and gas producers through technology workshops, resource centers, websites, newsletters, technical publications and other cooperative outreach efforts. PTTC's Headquarters (HQ) staff receives direction from a National Board of Directors predominantly comprised of American natural gas and oil producers to plan and manage the overall technology transfer program. PTTC HQ implements a comprehensive communications program by interconnecting the talents of the National Board, 10 Regional Producer Advisory Groups (PAG) and the RLOs with industry across the U.S. PTTC effectively combines federal funding through the Department of Energy's (DOE) Office of Fossil Energy, namely the Strategic Center for Natural Gas and Oil with state and industry contributions to share application of upstream technologies. Ultimately, these efforts factor in to provide a safe, secure and reliable energy supply for American consumers. This integrated resource base, combined with industry volunteers guiding PTTC's activities and the dedication of national and regional staff, are achieving notable results regarding domestic production figures. PTTC is increasingly recognized as a critical resource for information and access to technologies by providing direct contact with research, development and demonstration (RD&D) results. A key to the program is demonstrating proven technologies that can be applied broadly and rapidly. This technical progress report summarizes PTTC's accomplishments during

  18. Measurement-Device-Independent Quantum Cryptography

    Science.gov (United States)

    Tang, Zhiyuan

    Quantum key distribution (QKD) enables two legitimate parties to share a secret key even in the presence of an eavesdropper. The unconditional security of QKD is based on the fundamental laws of quantum physics. Original security proofs of QKD are based on a few assumptions, e.g., perfect single photon sources and perfect single-photon detectors. However, practical implementations of QKD systems do not fully comply with such assumptions due to technical limitations. The gap between theory and implementations leads to security loopholes in most QKD systems, and several attacks have been launched on sophisticated QKD systems. Particularly, the detectors have been found to be the most vulnerable part of QKD. Much effort has been put to build side-channel-free QKD systems. Solutions such as security patches and device-independent QKD have been proposed. However, the former are normally ad-hoc, and cannot close unidentified loopholes. The latter, while having the advantages of removing all assumptions on devices, is impractical to implement today. Measurement-device-independent QKD (MDI-QKD) turns out to be a promising solution to the security problem of QKD. In MDI-QKD, all security loopholes, including those yet-to-be discovered, have been removed from the detectors, the most critical part in QKD. In this thesis, we investigate issues related to the practical implementation and security of MDI-QKD. We first present a demonstration of polarization-encoding MDI-QKD. Taking finite key effect into account, we achieve a secret key rate of 0.005 bit per second (bps) over 10 km spooled telecom fiber, and a 1600-bit key is distributed. This work, together with other demonstrations, shows the practicality of MDI-QKD. Next we investigate a critical assumption of MDI-QKD: perfect state preparation. We apply the loss-tolerant QKD protocol and adapt it to MDI-QKD to quantify information leakage due to imperfect state preparation. We then present an experimental demonstration of

  19. Independence and totalness of subspaces in phase space methods

    Science.gov (United States)

    Vourdas, A.

    2018-04-01

    The concepts of independence and totalness of subspaces are introduced in the context of quasi-probability distributions in phase space, for quantum systems with finite-dimensional Hilbert space. It is shown that due to the non-distributivity of the lattice of subspaces, there are various levels of independence, from pairwise independence up to (full) independence. Pairwise totalness, totalness and other intermediate concepts are also introduced, which roughly express that the subspaces overlap strongly among themselves, and they cover the full Hilbert space. A duality between independence and totalness, that involves orthocomplementation (logical NOT operation), is discussed. Another approach to independence is also studied, using Rota's formalism on independent partitions of the Hilbert space. This is used to define informational independence, which is proved to be equivalent to independence. As an application, the pentagram (used in discussions on contextuality) is analysed using these concepts.

  20. Accelerated Dimension-Independent Adaptive Metropolis

    KAUST Repository

    Chen, Yuxin

    2016-10-27

    This work describes improvements by algorithmic and architectural means to black-box Bayesian inference over high-dimensional parameter spaces. The well-known adaptive Metropolis (AM) algorithm [H. Haario, E. Saksman, and J. Tamminen, Bernoulli, (2001), pp. 223--242] is extended herein to scale asymptotically uniformly with respect to the underlying parameter dimension for Gaussian targets, by respecting the variance of the target. The resulting algorithm, referred to as the dimension-independent adaptive Metropolis (DIAM) algorithm, also shows improved performance with respect to adaptive Metropolis on non-Gaussian targets. This algorithm is further improved, and the possibility of probing high-dimensional (with dimension $d \\\\geq 1000$) targets is enabled, via GPU-accelerated numerical libraries and periodically synchronized concurrent chains (justified a posteriori). Asymptotically in dimension, this GPU implementation exhibits a factor of four improvement versus a competitive CPU-based Intel MKL (math kernel library) parallel version alone. Strong scaling to concurrent chains is exhibited, through a combination of longer time per sample batch (weak scaling) with fewer necessary samples to convergence. The algorithm performance is illustrated on several Gaussian and non-Gaussian target examples, in which the dimension may be in excess of one thousand.

  1. Measurement device-independent quantum dialogue

    Science.gov (United States)

    Maitra, Arpita

    2017-12-01

    Very recently, the experimental demonstration of quantum secure direct communication (QSDC) with state-of-the-art atomic quantum memory has been reported (Zhang et al. in Phys Rev Lett 118:220501, 2017). Quantum dialogue (QD) falls under QSDC where the secrete messages are communicated simultaneously between two legitimate parties. The successful experimental demonstration of QSDC opens up the possibilities for practical implementation of QD protocols. Thus, it is necessary to analyze the practical security issues of QD protocols for future implementation. Since the very first proposal for QD by Nguyen (Phys Lett A 328:6-10, 2004), a large number of variants and extensions have been presented till date. However, all of those leak half of the secret bits to the adversary through classical communications of the measurement results. In this direction, motivated by the idea of Lo et al. (Phys Rev Lett 108:130503, 2012), we propose a measurement device-independent quantum dialogue scheme which is resistant to such information leakage as well as side-channel attacks. In the proposed protocol, Alice and Bob, two legitimate parties, are allowed to prepare the states only. The states are measured by an untrusted third party who may himself behave as an adversary. We show that our protocol is secure under this adversarial model. The current protocol does not require any quantum memory, and thus, it is inherently robust against memory attacks. Such robustness might not be guaranteed in the QSDC protocol with quantum memory (Zhang et al. 2017).

  2. Cerebral asymmetries: complementary and independent processes.

    Directory of Open Access Journals (Sweden)

    Gjurgjica Badzakova-Trajkov

    Full Text Available Most people are right-handed and left-cerebrally dominant for speech, leading historically to the general notion of left-hemispheric dominance, and more recently to genetic models proposing a single lateralizing gene. This hypothetical gene can account for higher incidence of right-handers in those with left cerebral dominance for speech. It remains unclear how this dominance relates to the right-cerebral dominance for some nonverbal functions such as spatial or emotional processing. Here we use functional magnetic resonance imaging with a sample of 155 subjects to measure asymmetrical activation induced by speech production in the frontal lobes, by face processing in the temporal lobes, and by spatial processing in the parietal lobes. Left-frontal, right-temporal, and right-parietal dominance were all intercorrelated, suggesting that right-cerebral biases may be at least in part complementary to the left-hemispheric dominance for language. However, handedness and parietal asymmetry for spatial processing were uncorrelated, implying independent lateralizing processes, one producing a leftward bias most closely associated with handedness, and the other a rightward bias most closely associated with spatial attention.

  3. Spatially independent martingales, intersections, and applications

    CERN Document Server

    Shmerkin, Pablo

    2018-01-01

    The authors define a class of random measures, spatially independent martingales, which we view as a natural generalization of the canonical random discrete set, and which includes as special cases many variants of fractal percolation and Poissonian cut-outs. The authors pair the random measures with deterministic families of parametrized measures \\{\\eta_t\\}_t, and show that under some natural checkable conditions, a.s. the mass of the intersections is H�lder continuous as a function of t. This continuity phenomenon turns out to underpin a large amount of geometric information about these measures, allowing us to unify and substantially generalize a large number of existing results on the geometry of random Cantor sets and measures, as well as obtaining many new ones. Among other things, for large classes of random fractals they establish (a) very strong versions of the Marstrand-Mattila projection and slicing results, as well as dimension conservation, (b) slicing results with respect to algebraic curves a...

  4. Image classification independent of orientation and scale

    Science.gov (United States)

    Arsenault, Henri H.; Parent, Sebastien; Moisan, Sylvain

    1998-04-01

    The recognition of targets independently of orientation has become fairly well developed in recent years for in-plane rotation. The out-of-plane rotation problem is much less advanced. When both out-of-plane rotations and changes of scale are present, the problem becomes very difficult. In this paper we describe our research on the combined out-of- plane rotation problem and the scale invariance problem. The rotations were limited to rotations about an axis perpendicular to the line of sight. The objects to be classified were three kinds of military vehicles. The inputs used were infrared imagery and photographs. We used a variation of a method proposed by Neiberg and Casasent, where a neural network is trained with a subset of the database and a minimum distances from lines in feature space are used for classification instead of nearest neighbors. Each line in the feature space corresponds to one class of objects, and points on one line correspond to different orientations of the same target. We found that the training samples needed to be closer for some orientations than for others, and that the most difficult orientations are where the target is head-on to the observer. By means of some additional training of the neural network, we were able to achieve 100% correct classification for 360 degree rotation and a range of scales over a factor of five.

  5. Fluoride absorption: independence from plasma fluoride levels

    International Nuclear Information System (INIS)

    Whitford, G.M.; Williams, J.L.

    1986-01-01

    The concept that there are physiologic mechanisms to homeostatically regulate plasma fluoride concentrations has been supported by results in the literature suggesting an inverse relationship between plasma fluoride levels and the absorption of the ion from the gastrointestinal tract of the rat. The validity of the relationship was questioned because of possible problems in the experimental design. The present work used four different methods to evaluate the effect of plasma fluoride levels on the absorption of the ion in rats: (i) the percentage of the daily fluoride intake that was excreted in the urine; (ii) the concentration of fluoride in femur epiphyses; (iii) the net areas under the time-plasma fluoride concentration curves after intragastric fluoride doses; and (iv) the residual amounts or fluoride in the gastrointestinal tracts after the intragastric fluoride doses. None of these methods indicated that plasma fluoride levels influence the rate or the degree or fluoride absorption. It was concluded that, unless extremely high plasma fluoride levels are involved (pharmacologic or toxic doses), the absorption of the ion is independent of plasma levels. The results provide further evidence that plasma fluoride concentrations are not homeostatically regulated

  6. Microenvironmental independence associated with tumor progression.

    Science.gov (United States)

    Anderson, Alexander R A; Hassanein, Mohamed; Branch, Kevin M; Lu, Jenny; Lobdell, Nichole A; Maier, Julie; Basanta, David; Weidow, Brandy; Narasanna, Archana; Arteaga, Carlos L; Reynolds, Albert B; Quaranta, Vito; Estrada, Lourdes; Weaver, Alissa M

    2009-11-15

    Tumor-microenvironment interactions are increasingly recognized to influence tumor progression. To understand the competitive dynamics of tumor cells in diverse microenvironments, we experimentally parameterized a hybrid discrete-continuum mathematical model with phenotypic trait data from a set of related mammary cell lines with normal, transformed, or tumorigenic properties. Surprisingly, in a resource-rich microenvironment, with few limitations on proliferation or migration, transformed (but not tumorigenic) cells were most successful and outcompeted other cell types in heterogeneous tumor simulations. Conversely, constrained microenvironments with limitations on space and/or growth factors gave a selective advantage to phenotypes derived from tumorigenic cell lines. Analysis of the relative performance of each phenotype in constrained versus unconstrained microenvironments revealed that, although all cell types grew more slowly in resource-constrained microenvironments, the most aggressive cells were least affected by microenvironmental constraints. A game theory model testing the relationship between microenvironment resource availability and competitive cellular dynamics supports the concept that microenvironmental independence is an advantageous cellular trait in resource-limited microenvironments.

  7. 'Smart' homes and telecare for independent living.

    Science.gov (United States)

    Tang, P; Venables, T

    2000-01-01

    Telecare services and 'smart' homes share a common technological base in information technology and telecommunications. There is growing interest in both telecare services and smart homes, although they have been studied in isolation. Telecare has been driven largely by perceived cost savings and improved service delivery to the home, leading to improved quality of life and independent living. Smart homes are also expected to provide better and safer living conditions. The integration of the two should produce more secure and autonomous living. There are different forms of telecare services, as there are different types of smart homes, each ranging from basic systems involving the use of alarms and the ordinary telephone to intelligent monitoring with sensors and interactive communication. The introduction of these systems has policy implications, such as the need for coordination between health, social services and housing policy makers, which will reduce duplication and inefficient allocation of resources. Successful delivery of telecare to the home is as much dependent on the construction and condition of the housing stock as it is on the ability of the care provider to meet users' needs. If the UK National Health Service (NHS) could replace a significant proportion of domiciliary nursing visits by telephone calls, then savings of up of 200 million Pounds per annum would be possible.

  8. Independent System Operators and Biomass Power

    International Nuclear Information System (INIS)

    Porter, Kevin L.

    1999-01-01

    Since the Federal Energy Regulatory Commission issued its landmark open access transmission rule in 1996, the idea of creating and establishing independent system operators (ISOs) has gained momentum. ISOs may help combine individual utility transmission systems into more regional transmission networks, which ultimately will allow biomass companies to transmit power over longer distances while paying a single transmission rate. To the extent that ISOs are combined or operated with power exchanges, however, biomass companies will likely face even more competitive market pressures. Few operators have experience with ISOs and power exchanges, but preliminary results show that short-term electricity market prices are probably too low for most biomass companies to compete against. Without policy measures, biomass companies may have to pursue strategic opportunities with short-term, spot-market sales; direct bilateral sales to customers; alternative power exchanges; and perhaps a ''green'' power market and sales to ancillary service markets. In addition, prices will likely be more volatile in a restructured market so biomass generators should be selling during those times

  9. Independent Biotechnology: The Innovation-Regulation Dilemma

    Energy Technology Data Exchange (ETDEWEB)

    Althouse, P. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Prosnitz, D. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Velsko, S. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2016-11-03

    The Center for Global Security Research at Lawrence Livermore National Laboratory convened a workshop on August 19, 2016 to consider “Independent Biotechnology: The Innovation-­Regulation Dilemma”. The topic was motivated by the observation that non-­government funded biotechnology research and development activities have grown and diversified tremendously over the past decade. This sector encompasses a broad range of actors and activities: individuals with private laboratories, community “hackerspaces,” biotechnology incubators, and individual startups. Motivations and aspirations are diverse and include such things as personal curiosity, community education, the invention of new products or services, and even the realization of certain economic, political, or social goals. One driving force is the “democratization” of ever more powerful biological technologies, allowing individual citizens and groups access to capabilities that have traditionally only been available to researchers in universities, research institutes, national laboratories, and large commercial concerns. Another is the rise of alternative financing mechanisms such as “crowdsourcing,” which ostensibly provide greater freedom to innovate, and greater public visibility, but entail looser management oversight and transparency.

  10. Model-independent Exoplanet Transit Spectroscopy

    Science.gov (United States)

    Aronson, Erik; Piskunov, Nikolai

    2018-05-01

    We propose a new data analysis method for obtaining transmission spectra of exoplanet atmospheres and brightness variation across the stellar disk from transit observations. The new method is capable of recovering exoplanet atmosphere absorption spectra and stellar specific intensities without relying on theoretical models of stars and planets. We simultaneously fit both stellar specific intensity and planetary radius directly to transit light curves. This allows stellar models to be removed from the data analysis. Furthermore, we use a data quality weighted filtering technique to achieve an optimal trade-off between spectral resolution and reconstruction fidelity homogenizing the signal-to-noise ratio across the wavelength range. Such an approach is more efficient than conventional data binning onto a low-resolution wavelength grid. We demonstrate that our analysis is capable of reproducing results achieved by using an explicit quadratic limb-darkening equation and that the filtering technique helps eliminate spurious spectral features in regions with strong telluric absorption. The method is applied to the VLT FORS2 observations of the exoplanets GJ 1214 b and WASP-49 b, and our results are in agreement with previous studies. Comparisons between obtained stellar specific intensity and numerical models indicates that the method is capable of accurately reconstructing the specific intensity. The proposed method enables more robust characterization of exoplanetary atmospheres by separating derivation of planetary transmission and stellar specific intensity spectra (that is model-independent) from chemical and physical interpretation.

  11. Source-Independent Quantum Random Number Generation

    Science.gov (United States)

    Cao, Zhu; Zhou, Hongyi; Yuan, Xiao; Ma, Xiongfeng

    2016-01-01

    Quantum random number generators can provide genuine randomness by appealing to the fundamental principles of quantum mechanics. In general, a physical generator contains two parts—a randomness source and its readout. The source is essential to the quality of the resulting random numbers; hence, it needs to be carefully calibrated and modeled to achieve information-theoretical provable randomness. However, in practice, the source is a complicated physical system, such as a light source or an atomic ensemble, and any deviations in the real-life implementation from the theoretical model may affect the randomness of the output. To close this gap, we propose a source-independent scheme for quantum random number generation in which output randomness can be certified, even when the source is uncharacterized and untrusted. In our randomness analysis, we make no assumptions about the dimension of the source. For instance, multiphoton emissions are allowed in optical implementations. Our analysis takes into account the finite-key effect with the composable security definition. In the limit of large data size, the length of the input random seed is exponentially small compared to that of the output random bit. In addition, by modifying a quantum key distribution system, we experimentally demonstrate our scheme and achieve a randomness generation rate of over 5 ×103 bit /s .

  12. The Road to Independently Understandable Information

    Science.gov (United States)

    Habermann, T.; Robinson, E.

    2017-12-01

    The turn of the 21st century was a pivotal time in the Earth and Space Science information ecosystem. The Content Standard for Digital Geospatial Metadata (CSDGM) had existed for nearly a decade and ambitious new standards were just emerging. The U.S. Federal Geospatial Data Committee (FGDC) had extended many of the concepts from CSDGM into the International community with ISO 19115:2003 and the Consultative Committee for Space Data Systems (CCSDS) had migrated their Open Archival Information System (OAIS) Reference Model into an international standard (ISO 14721:2003). The OAIS model outlined the roles and responsibilities of archives with the principle role being preserving information and making it available to users, a "designated community", as a service to the data producer. It was mandatory for the archive to ensure that information is "independently understandable" to the designated community and to maintain that understanding through on-going partnerships between archives and designated communities. Standards can play a role in supporting these partnerships as designated communities expand across disciplinary and geographic boundaries. The ISO metadata standards include many capabilities that might make critical contributions to this goal. These include connections to resources outside of the metadata record (i.e. documentation) and mechanisms for ongoing incorporation of user feedback into the metadata stream. We will demonstrate these capabilities with examples of how they can increase understanding.

  13. [Emergency department triage: independent nursing intervention?].

    Science.gov (United States)

    Corujo Fontes, Sergio José

    2014-03-01

    The branch hospital triage aimed at, as well as exercised by nurses, has evolved to meet their needs to organize and make visible the nurses' duties. However, it is still not properly considered as independent nursing intervention. Evidencing practice triage nurse in hospital as experienced by their protagonists disclosed the possible causes of this paradoxical competence. In a sample of 41 nurses, of the 52 possible with previous experience in hospital triage in the Emergency Department of the Hospital General Dr. José Molina Orosa in Lanzarote, the nurses themselves carried out an opinion survey that group together statements about different aspects of the triaje nurse. In its results, 65.8% of those polled thought the triaje nursing training to be deficient and even though nearly half 48.7%, was considered competent to decide the level of emergency, 46.3% disagreed to take this task part of their duty. It is conclusive that the training received in hospital triage, regulated and sustained, is deficient, that is the main reason why professionals have their doubts to take on an activity they are not familiar with. Triage systems do not record the entire outcome of the nursing work and nursing methodology does not seem to be quite indicative for this task.

  14. Source-Independent Quantum Random Number Generation

    Directory of Open Access Journals (Sweden)

    Zhu Cao

    2016-02-01

    Full Text Available Quantum random number generators can provide genuine randomness by appealing to the fundamental principles of quantum mechanics. In general, a physical generator contains two parts—a randomness source and its readout. The source is essential to the quality of the resulting random numbers; hence, it needs to be carefully calibrated and modeled to achieve information-theoretical provable randomness. However, in practice, the source is a complicated physical system, such as a light source or an atomic ensemble, and any deviations in the real-life implementation from the theoretical model may affect the randomness of the output. To close this gap, we propose a source-independent scheme for quantum random number generation in which output randomness can be certified, even when the source is uncharacterized and untrusted. In our randomness analysis, we make no assumptions about the dimension of the source. For instance, multiphoton emissions are allowed in optical implementations. Our analysis takes into account the finite-key effect with the composable security definition. In the limit of large data size, the length of the input random seed is exponentially small compared to that of the output random bit. In addition, by modifying a quantum key distribution system, we experimentally demonstrate our scheme and achieve a randomness generation rate of over 5×10^{3}  bit/s.

  15. Independent particle Schroedinger Fluid: moments of inertia

    International Nuclear Information System (INIS)

    Kan, K.K.; Griffin, J.J.

    1977-10-01

    This philosophy of the Single Particle Schroedinger Fluid, especially as regards the velocity fields which find such a natural role therein, is applied to the study of the moments of inertia of independent Fermion system. It is shown that three simplified systems exhibit the rigid-body rotational velocity field in the limit of large A, and that the leading deviations, both on the average and fluctuating, from this large A limit can be described analytically, and verified numerically. For a single particle in a Hill-Wheeler box the moments are studied numerically, and their large fluctuations identified with the specific energy level degeneracies of its parallelepiped shape. The full assemblage of these new and old results is addressed to the question of the necessary and sufficient condition that the moment have the rigid value. Counterexamples are utilized to reject some conditions, and the conjecture is argued that Unconstrained Shape Equilibrium might be the necessary and sufficient condition. The spheroidal square well problem is identified as a promising test case

  16. Datacube Interoperability, Encoding Independence, and Analytics

    Science.gov (United States)

    Baumann, Peter; Hirschorn, Eric; Maso, Joan

    2017-04-01

    Datacubes are commonly accepted as an enabling paradigm which provides a handy abstraction for accessing and analyzing the zillions of image files delivered by the manifold satellite instruments and climate simulations, among others. Additionally, datacubes are the classic model for statistical and OLAP datacubes, so a further information category can be integrated. From a standards perspective, spatio-temporal datacubes naturally are included in the concept of coverages which encompass regular and irregular grids, point clouds, and general meshes - or, more abstractly, digital representations of spatio-temporally varying phenomena. ISO 19123, which is identical to OGC Abstract Topic 6, gives a high-level abstract definition which is complemented by the OGC Coverage Implementation Schema (CIS) which is an interoperable, yet format independent concretization of the abstract model. Currently, ISO is working on adopting OGC CIS as ISO 19123-2; the existing ISO 19123 standard is under revision by one of the abstract authors and will become ISO 19123-1. The roadmap agreed by ISO further foresees adoption of the OGC Web Coverage Service (WCS) as an ISO standard so that a complete data and service model will exist. In 2016, INSPIRE has adopted WCS as Coverage Download Service, including the datacube analytics language Web Coverage Processing Service (WCPS). The rasdaman technology (www.rasdaman.org) is both OGC and INSPIRE Reference Implementation. In the global EarthServer initiative rasdaman database sizes are exceeding 250 TB today, heading for the Petabyte frontier well in 2017. Technically, CIS defines a compact, efficient model for representing multi-dimensional datacubes in several ways. The classical coverage cube defines a domain set (where are values?), a range set (what are these values?), and range type (what do the values mean?), as well as a "bag" for arbitrary metadata. With CIS 1.1, coordinate/value pair sequences have been added, as well as tiled

  17. Systems analysis-independent analysis and verification

    Energy Technology Data Exchange (ETDEWEB)

    Badin, J.S.; DiPietro, J.P. [Energetics, Inc., Columbia, MD (United States)

    1995-09-01

    The DOE Hydrogen Program is supporting research, development, and demonstration activities to overcome the barriers to the integration of hydrogen into the Nation`s energy infrastructure. Much work is required to gain acceptance of hydrogen energy system concepts and to develop them for implementation. A systems analysis database has been created that includes a formal documentation of technology characterization profiles and cost and performance information. Through a systematic and quantitative approach, system developers can understand and address important issues and thereby assure effective and timely commercial implementation. This project builds upon and expands the previously developed and tested pathway model and provides the basis for a consistent and objective analysis of all hydrogen energy concepts considered by the DOE Hydrogen Program Manager. This project can greatly accelerate the development of a system by minimizing the risk of costly design evolutions, and by stimulating discussions, feedback, and coordination of key players and allows them to assess the analysis, evaluate the trade-offs, and to address any emerging problem areas. Specific analytical studies will result in the validation of the competitive feasibility of the proposed system and identify system development needs. Systems that are investigated include hydrogen bromine electrolysis, municipal solid waste gasification, electro-farming (biomass gasifier and PEM fuel cell), wind/hydrogen hybrid system for remote sites, home electrolysis and alternate infrastructure options, renewable-based electrolysis to fuel PEM fuel cell vehicle fleet, and geothermal energy used to produce hydrogen. These systems are compared to conventional and benchmark technologies. Interim results and findings are presented. Independent analyses emphasize quality, integrity, objectivity, a long-term perspective, corporate memory, and the merging of technical, economic, operational, and programmatic expertise.

  18. Progranulin regulates neuronal outgrowth independent of Sortilin

    Directory of Open Access Journals (Sweden)

    Gass Jennifer

    2012-07-01

    Full Text Available Abstract Background Progranulin (PGRN, a widely secreted growth factor, is involved in multiple biological functions, and mutations located within the PGRN gene (GRN are a major cause of frontotemporal lobar degeneration with TDP-43-positive inclusions (FLTD-TDP. In light of recent reports suggesting PGRN functions as a protective neurotrophic factor and that sortilin (SORT1 is a neuronal receptor for PGRN, we used a Sort1-deficient (Sort1−/− murine primary hippocampal neuron model to investigate whether PGRN’s neurotrophic effects are dependent on SORT1. We sought to elucidate this relationship to determine what role SORT1, as a regulator of PGRN levels, plays in modulating PGRN’s neurotrophic effects. Results As the first group to evaluate the effect of PGRN loss in Grn knockout primary neuronal cultures, we show neurite outgrowth and branching are significantly decreased in Grn−/− neurons compared to wild-type (WT neurons. More importantly, we also demonstrate that PGRN overexpression can rescue this phenotype. However, the recovery in outgrowth is not observed following treatment with recombinant PGRN harboring missense mutations p.C139R, p.P248L or p.R432C, indicating that these mutations adversely affect the neurotrophic properties of PGRN. In addition, we also present evidence that cleavage of full-length PGRN into granulin peptides is required for increased neuronal outgrowth, suggesting that the neurotrophic functions of PGRN are contained within certain granulins. To further characterize the mechanism by which PGRN impacts neuronal morphology, we assessed the involvement of SORT1. We demonstrate that PGRN induced-outgrowth occurs in the absence of SORT1 in Sort1−/− cultures. Conclusion We demonstrate that loss of PGRN impairs proper neurite outgrowth and branching, and that exogenous PGRN alleviates this impairment. Furthermore, we determined that exogenous PGRN induces outgrowth independent of SORT1, suggesting another

  19. Quality Determinants of Independent Audits of Banks

    Directory of Open Access Journals (Sweden)

    José Alves Dantas

    2015-04-01

    Full Text Available Since DeAngelo's study (1981 on audit quality, the latter has been a topic well discussed in the international accounting literature; however, there is little evidence about audit quality in the financial market. In Brazil, studies on audit quality began only in the 2000s, although without a specific focus on banks. The purpose of this study was to identify the quality determinants of audit work in Brazilian banking institutions. Using the practice of earnings management as a proxy for audit quality - more specifically, the discretionary accruals related to the process of the constitution of the Loan Loss Provision (LLP - tests were performed based on the quarterly information of commercial and multipleservice banks and savings banks from 2001 to 2012. Empirical tests have shown that the quality of audit work has several types of relationships as follows: negative with the client importance level for the auditor; negative with the works after the sixth year of the contract; positive with the establishment of the Audit Committee by the banks; positive with the judgment of punitive administrative proceedings against independent auditors; and positive with the level of rigor of the regulatory environment. Of the tested hypotheses, three were not confirmed empirically. The first hypothesis predicted an association between audit quality and the auditor degree of specialization in the banking industry. The second hypothesis predicted that audit quality would be negatively correlated with the degree of concentration of audit activity within the National Financial System (Sistema Financeiro Nacional - SFN. The third hypothesis predicted that audit quality would be lower when the auditorclient relationship is of a short term. The results of the study contribute to the debate concerning the role of auditors in the transparency and solidity of the financial system, including their role as a complementary or auxiliary supervisor.

  20. Political Attitudes Develop Independently of Personality Traits

    Science.gov (United States)

    Hatemi, Peter K.; Verhulst, Brad

    2015-01-01

    The primary assumption within the recent personality and political orientations literature is that personality traits cause people to develop political attitudes. In contrast, research relying on traditional psychological and developmental theories suggests the relationship between most personality dimensions and political orientations are either not significant or weak. Research from behavioral genetics suggests the covariance between personality and political preferences is not causal, but due to a common, latent genetic factor that mutually influences both. The contradictory assumptions and findings from these research streams have yet to be resolved. This is in part due to the reliance on cross-sectional data and the lack of longitudinal genetically informative data. Here, using two independent longitudinal genetically informative samples, we examine the joint development of personality traits and attitude dimensions to explore the underlying causal mechanisms that drive the relationship between these features and provide a first step in resolving the causal question. We find change in personality over a ten-year period does not predict change in political attitudes, which does not support a causal relationship between personality traits and political attitudes as is frequently assumed. Rather, political attitudes are often more stable than the key personality traits assumed to be predicting them. Finally, the results from our genetic models find that no additional variance is accounted for by the causal pathway from personality traits to political attitudes. Our findings remain consistent with the original construction of the five-factor model of personality and developmental theories on attitude formation, but challenge recent work in this area. PMID:25734580

  1. Political attitudes develop independently of personality traits.

    Science.gov (United States)

    Hatemi, Peter K; Verhulst, Brad

    2015-01-01

    The primary assumption within the recent personality and political orientations literature is that personality traits cause people to develop political attitudes. In contrast, research relying on traditional psychological and developmental theories suggests the relationship between most personality dimensions and political orientations are either not significant or weak. Research from behavioral genetics suggests the covariance between personality and political preferences is not causal, but due to a common, latent genetic factor that mutually influences both. The contradictory assumptions and findings from these research streams have yet to be resolved. This is in part due to the reliance on cross-sectional data and the lack of longitudinal genetically informative data. Here, using two independent longitudinal genetically informative samples, we examine the joint development of personality traits and attitude dimensions to explore the underlying causal mechanisms that drive the relationship between these features and provide a first step in resolving the causal question. We find change in personality over a ten-year period does not predict change in political attitudes, which does not support a causal relationship between personality traits and political attitudes as is frequently assumed. Rather, political attitudes are often more stable than the key personality traits assumed to be predicting them. Finally, the results from our genetic models find that no additional variance is accounted for by the causal pathway from personality traits to political attitudes. Our findings remain consistent with the original construction of the five-factor model of personality and developmental theories on attitude formation, but challenge recent work in this area.

  2. Smile (System/Machine-Independent Local Environment)

    Energy Technology Data Exchange (ETDEWEB)

    Fletcher, J.G.

    1988-04-01

    This document defines the characteristics of Smile, a System/machine-independent local environment. This environment consists primarily of a number of primitives (types, macros, procedure calls, and variables) that a program may use; these primitives provide facilities, such as memory allocation, timing, tasking and synchronization beyond those typically provided by a programming language. The intent is that a program will be portable from system to system and from machine to machine if it relies only on the portable aspects of its programming language and on the Smile primitives. For this to be so, Smile itself must be implemented on each system and machine, most likely using non-portable constructions; that is, while the environment provided by Smile is intended to be portable, the implementation of Smile is not necessarily so. In order to make the implementation of Smile as easy as possible and thereby expedite the porting of programs to a new system or a new machine, Smile has been defined to provide a minimal portable environment; that is, simple primitives are defined, out of which more complex facilities may be constructed using portable procedures. The implementation of Smile can be as any of the following: the underlying software environment for the operating system of an otherwise {open_quotes}bare{close_quotes} machine, a {open_quotes}guest{close_quotes} system environment built upon a preexisting operating system, an environment within a {open_quotes}user{close_quotes} process run by an operating system, or a single environment for an entire machine, encompassing both system and {open_quotes}user{close_quotes} processes. In the first three of these cases the tasks provided by Smile are {open_quotes}lightweight processes{close_quotes} multiplexed within preexisting processes or the system, while in the last case they also include the system processes themselves.

  3. Economic efficiency, independent power producers and wheeling

    International Nuclear Information System (INIS)

    Fytche, E.L.

    1991-01-01

    Traditionally, electric utilities have sought to decrease the cost of production by such means as merit order running of machines, by improving equipment efficiency, by fuel mix, by interconnection and exchange of cheap energy, and by unit participation and firm purchase and sale contracts for long term savings. In the ''new look'', it was suggested that financial and technical competition is not enough, and that economic gains could be achieved through fostering independent power producers, i.e., non-utility generators (NUG's), greater exchanges of economy energy, unrestricted access to the transmission network for moving cheap energy through facilities of third parties, and by bidding to supply energy to non-generators, etc. Naturally, the proposals to change the comfortable and time-hallowed practices by which utility business had been carried out in the past has created an ongoing debate both pro and con, much of it acrimonious, and, unfortunately, some of it ill-informed. The turmoil in the political context impacts on a utility's technical and financial planners, and on their managements, all of whom contribute to justifying and maintaining the flow of capital to the industry and energy to the customer. They must now seek new ways to implement both short- and long-term planning of power supply. Some of the factors that were neglected in the past will demand more attention in the future. This paper discusses some of the costs that, under the anticipated modus operandi, must be integrated into the planning process while meeting the new challenges. The costs are those relating to third-parties, costs of transmission constraints, and costs of wheeling. The opinion is ventured that much of the efficiency improvement anticipated during the debate has already been achieved by conscientious utility managements. (author)

  4. Model-independent and quasi-model-independent search for new physics at CDF

    International Nuclear Information System (INIS)

    Aaltonen, T.; Maki, T.; Mehtala, P.; Orava, R.; Osterberg, K.; Saarikko, H.; van Remortel, N.; Abulencia, A.; Budd, S.; Ciobanu, C. I.; Errede, D.; Errede, S.; Gerberich, H.; Grundler, U.; Junk, T. R.; Kraus, J.; Marino, C. P.; Neubauer, M. S.; Norniella, O.; Pitts, K.

    2008-01-01

    Data collected in run II of the Fermilab Tevatron are searched for indications of new electroweak scale physics. Rather than focusing on particular new physics scenarios, CDF data are analyzed for discrepancies with respect to the standard model prediction. A model-independent approach (Vista) considers the gross features of the data and is sensitive to new large cross section physics. A quasi-model-independent approach (Sleuth) searches for a significant excess of events with large summed transverse momentum and is particularly sensitive to new electroweak scale physics that appears predominantly in one final state. This global search for new physics in over 300 exclusive final states in 927 pb -1 of pp collisions at √(s)=1.96 TeV reveals no such significant indication of physics beyond the standard model.

  5. 38 CFR 21.160 - Independent living services.

    Science.gov (United States)

    2010-07-01

    ... furnished: (1) As part of a program to achieve rehabilitation to the point of employability; (2) As part of...) Evaluation of independent living potential; (ii) Training in independent living skills; (iii) Attendant care...

  6. Biological functionalization of drug delivery carriers to bypass size restrictions of receptor-mediated endocytosis independently from receptor targeting.

    Science.gov (United States)

    Ansar, Maria; Serrano, Daniel; Papademetriou, Iason; Bhowmick, Tridib Kumar; Muro, Silvia

    2013-12-23

    Targeting of drug carriers to cell-surface receptors involved in endocytosis is commonly used for intracellular drug delivery. However, most endocytic receptors mediate uptake via clathrin or caveolar pathways associated with ≤200-nm vesicles, restricting carrier design. We recently showed that endocytosis mediated by intercellular adhesion molecule 1 (ICAM-1), which differs from clathrin- and caveolae-mediated pathways, allows uptake of nano- and microcarriers in cell culture and in vivo due to recruitment of cellular sphingomyelinases to the plasmalemma. This leads to ceramide generation at carrier binding sites and formation of actin stress-fibers, enabling engulfment and uptake of a wide size-range of carriers. Here we adapted this paradigm to enhance uptake of drug carriers targeted to receptors associated with size-restricted pathways. We coated sphingomyelinase onto model (polystyrene) submicro- and microcarriers targeted to clathrin-associated mannose-6-phosphate receptor. In endothelial cells, this provided ceramide enrichment at the cell surface and actin stress-fiber formation, modifying the uptake pathway and enhancing carrier endocytosis without affecting targeting, endosomal transport, cell-associated degradation, or cell viability. This improvement depended on the carrier size and enzyme dose, and similar results were observed for other receptors (transferrin receptor) and cell types (epithelial cells). This phenomenon also enhanced tissue accumulation of carriers after intravenous injection in mice. Hence, it is possible to maintain targeting toward a selected receptor while bypassing natural size restrictions of its associated endocytic route by functionalization of drug carriers with biological elements mimicking the ICAM-1 pathway. This strategy holds considerable promise to enhance flexibility of design of targeted drug delivery systems.

  7. Independents in the local politics of post-communist Romania

    OpenAIRE

    Enache, Ion

    2011-01-01

    Aiming at filling a gap in the existing literature, this paper advances the analysis of available alternatives to party representation, namely independent candidatures. For that reason, we consider the context of Eastern Europe, and particularly the last decade when a considerable number of independent candidatures have been advanced. Particularly, the Romanian political system provides one viable example for the examination of independent candidacies, with numerous independents running in th...

  8. Our 1% Problem: Independent Schools and the Income Gap

    Science.gov (United States)

    Bartels, Fred

    2012-01-01

    The subject of independent schools and inequality is rife with contradictions. In some ways, independent schools work to ameliorate inequities. In other ways, they reinforce and exacerbate them. Those in independent schools who work on social justice, equity, and diversity issues deal with these contradictions every day. Most believe, most of the…

  9. 12 CFR 363.3 - Independent public accountant.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Independent public accountant. 363.3 Section... POLICY ANNUAL INDEPENDENT AUDITS AND REPORTING REQUIREMENTS § 363.3 Independent public accountant. (a... public accountant to audit and report on its annual financial statements in accordance with generally...

  10. Fuzzy AHP Analysis on Enterprises’ Independent Innovation Capability Evaluation

    Science.gov (United States)

    Zhu, Yu; Lei, Huai-ying

    Independent innovation has become a key factor in the rapid and healthy development of the enterprises. Therefore, an effective and reasonable comprehensive evaluation on the independent innovation capability of the businesses is especially important. This paper applies fuzzy AHP in the evaluation of the independent innovation capability of the businesses, and validates the rationality and feasibility of the evaluation methods and the indicators.

  11. 45 CFR 96.136 - Independent peer review.

    Science.gov (United States)

    2010-10-01

    ... influence the quality of the services provided. (d) As part of the independent peer review, the reviewers... 45 Public Welfare 1 2010-10-01 2010-10-01 false Independent peer review. 96.136 Section 96.136... Abuse Prevention and Treatment Block Grant § 96.136 Independent peer review. (a) The State shall for the...

  12. Development Parenting Model to Increase the Independence of Children

    Science.gov (United States)

    Sunarty, Kustiah; Dirawan, Gufran Darma

    2015-01-01

    This study examines parenting and the child's independence model. The research problem is whether there is a relationship between parenting and the child's independence. The purpose of research is to determine: firstly, the type of parenting in an effort to increase the independence of the child; and the relationship between parenting models and…

  13. Propensity of Unqualified Audit Reports and Auditors' Independence ...

    African Journals Online (AJOL)

    The need for auditors‟ independence is very crucial for the success of audit process. Independence of the auditors manifests in technical, investigative and reporting forms. For the audit report to be publicly accepted as reflecting the true and fair view the auditors must be seen to be indeed truly independent. One way the ...

  14. Functional Independence Measure Penderita Cedera Servikal

    Directory of Open Access Journals (Sweden)

    Muhammad Zafrullah Arifin

    2013-09-01

    Full Text Available Cervical spine injury is one of the most common spinal cord injuries in trauma patients. From 100,000 spinal cord injury cases reported in the United States of America (2008, 2/3 involved cervical spine injury. American Spinal Cord Injury Association (ASIA Impairment Score is used as an initial assessment but further prognostic outcome of these patients is often not paid enough attention. The objective of this study was to find the value of functional independence measure (FIM cervical spine injury patients with conservative management and correlation with age, sex, type of trauma, onset of trauma, cervical bone abnormalities, type of spinal lesion and ASIA Impairment Score. A prospective cohort study was performed to all patients with cervical spine injury which fullfil the inclusion criteria treated in Neurosurgery Department of Dr. Hasan Sadikin Hospital Bandung. The subjects were classified based on age, sex, single/multiple trauma, acute/chronic, cervical bone abnormalities, complete/incomplete lesion, ASIA impairment score and initial complication. The patients were performed to FIM examination in Outpatient clinic of Neurosurgery. T-test and chi-square test with p<0.05 were done to analyze the data. There were 17 cervical spine injury patients treated in Neurosurgery Department of Dr. Hasan Sadikin Hospital Bandung during April 2009–April 2010. The average FIM value of cervical spine injury in those patients was 4+1.63 by cohort prospective study. There were no correlation between FIM value with age (p=0.064, sex (p=0.144, type of trauma (p=0.959, onset of trauma (p=0.220 and cervical bone abnormalities (p=0.869. We found a significant correlation between FIM value with type of cervical spine lesion (p=0.037 and ASIA Impairment Score (p<0.001 in cervical spine patients. In conclusion, type of cervical spine lesion and ASIA impairment score have significant correlation with FIM value of patients in 3 months after cervical injury.

  15. Targeted Technology Transfer to US Independents

    Energy Technology Data Exchange (ETDEWEB)

    E. Lance Cole

    2009-09-30

    The Petroleum Technology Transfer Council (PTTC) was established by domestic crude oil and natural gas producers, working in conjunction with the Independent Petroleum Association of America (IPAA), the U.S. Department of Energy (DOE) and selected universities, in 1994 as a national not-for-profit organization. Its goal is to transfer Exploration and Production (E&P) technology to the domestic upstream petroleum industry, in particular to the small independent operators. PTTC connects producers, technology providers and innovators, academia, and university/industry/government research and development (R&D) groups. From inception PTTC has received federal funding through DOE's oil and natural gas program managed by the National Energy Technology Laboratory (NETL). With higher funding available in its early years, PTTC was able to deliver well more than 100 workshops per year, drawing 6,000 or more attendees per year. Facing the reality of little or no federal funding in the 2006-2007 time frame, PTTC and the American Association of Petroleum Geologists (AAPG) worked together for PTTC to become a subsidiary organization of AAPG. This change brings additional organizational and financial resources to bear for PTTC's benefit. PTTC has now been 'powered by AAPG' for two full fiscal years. There is a clear sense that PTTC has stabilized and is strengthening its regional workshop and national technology transfer programs and is becoming more entrepreneurial in exploring technology transfer opportunities beyond its primary DOE contract. Quantitative accomplishments: PTTC has maintained its unique structure of a national organization working through Regional Lead Organizations (RLOs) to deliver local, affordable workshops. During the contract period PTTC consolidated from 10 to six regions efficiency and alignment with AAPG sections. The number of workshops delivered by its RLOs during the contract period is shown below. Combined attendance over the

  16. The price of independents: an analysis of the independent power sector in England and Wales

    International Nuclear Information System (INIS)

    Branston, J. Robert

    2002-01-01

    This paper presents a focused analysis of the role of entrants into the electricity generation market since privatisation. It examines subsequent developments in the market and in the industry's structure and performance. The analysis draws heavily upon new information gained from telephone interviews with many of those involved with the so-called 'independent power producers' (IPPs), as well as information in the existing literature. Our key finding is that IPP entry has not significantly increased competition and has adversely affected the future viability of the electricity system. We attribute these failures to the very policies that encouraged the initial entry of the IPPs

  17. Expertise and contra expertise independence and transparency; Expertises -contre expertises independance et transparence

    Energy Technology Data Exchange (ETDEWEB)

    Abarnou, G; Ades, Y; Ancelin, G; Balle, St; Bardy, J Ch; Beringer, F; Blanc, M; Bontoux, J; Bovy, M; Brunet, F; Calafat, A; Cartier, M; Constant, H; Delcourt, R; Duvert, J C; Eichholtzer, F; Fernandez, P; Fernex, S; Foechterle, A; Gatesoupe, J P; Geneau, Ch; Goerg, C; Gourod, A; Graschaire, G; Hubscher Ibert, J; Jaegert, M; Lacoste, A C; Lacote, J P; Laroche, D; Lazar, Ph; Lelievre, D; Levasseur, E; Levent, L; Louvat, D; Manon, Ch; Maugein, J; Melguen, M; Mouchet, Ch; Mourat, J P; Naegelen, L; Niquet, G; Perves, J P; Potelet, P; Regent, A; Romann, J M; Rossa, N; Saut, C; Sazy, Ch; Schmitt, P; Sene, M; Sene, Raymond; Sornein, J F; Sugier, A; Tfibel, V; Uhart, M; Vidal, J; Vieillard Baron, B; Vigny, P; Walgenwitz, G; Wiest, A; Wisselmann, R; Zuberbuhler, A

    2006-07-01

    About sixty participants: members of C.L.I., academics, elected representatives, manufacturers, representatives of association, institutional, crossed their experiences. The debate was mainly centred on the role of the expert, the limits of its intervention and its independence. The presented titles are following: experiences of two C.L.I. in expertise; the work of communication of the nuclear experts; interest and limits of the expertise; presentation of the I.R.S.N. and the D.G.S.N.R.; expertise: problems and experiences; presentation of the works realised in work group; the considerations of the C.S.S.I.N.. (N.C.)

  18. Targeted Technology Transfer to US Independents

    Energy Technology Data Exchange (ETDEWEB)

    Schatzinger, Viola [Petroleum Tech. Transfer Council, Tulsa, OK (United States); Chapman, Kathy [Petroleum Tech. Transfer Council, Tulsa, OK (United States); Lovendahl, Kristi [Petroleum Tech. Transfer Council, Tulsa, OK (United States)

    2014-09-30

    The Petroleum Technology Transfer Council (PTTC) is a unique not-for-profit network that focuses on transferring Exploration and Production (E&P) technology to the domestic oil and natural gas producing industry. PTTC connects producers, technology providers and innovators, academia, research and development (R&D) consortiums and governments. Local affordable workshops delivered by Regional Lead Organizations (RLOs), which are typically a university or geological survey, are a primary tool. PTTC also maintains a website network, issues a national newsletter, provides a column in a major trade publication, and exhibits at major industry events. It also encourages industry to ask technology-related questions, striving to find relevant answers that will save questioners significant time. Working since late 1993, the PTTC network has a proven track record of providing industry with technology insights they can apply. Volunteers at the regional and national level provide key guidance regarding where to focus technical effort and help connect PTTC with industry. At historical funding levels, PTTC had been able to hold well more than 100 workshops per year, drawing 6,000+ attendees. As funding decreased in the early 2000s, the level of activity decreased and PTTC sought a merger with the American Association of Petroleum Geologists (AAPG), becoming an AAPG-managed organization at the start of FY08. This relationship with AAPG was terminated by mutual consent in May 2011 and PTTC once again operates independently. Chris Hall, California continued to serve as Chairman of the Board of Directors until December 2013. At the time PTTC reorganized into a RLO led organization with Mary Carr and Jeremy Viscomi as co-Executive Directors. Jerry Anderson became the Chairman of the PTTC Board of Directors and Chris Hall continues to serve on the Board. Workshop activity stabilized at 55-65 workshops per year averaging 3,100 attendees. FY14 represented the fifth year in a multi

  19. Independent center, independent electron approximation for dynamics of molecules and clusters

    International Nuclear Information System (INIS)

    McGuire, J.H.; Straton, J.C.; Wang, J.; Wang, Y.D.; Weaver, O.L.; Corchs, S.E.; Rivarola, R.D.

    1996-01-01

    A formalism is developed for evaluating probabilities and cross sections for multiple-electron transitions in scattering of molecules and clusters by charged collision partners. First, the molecule is divided into subclusters each made up of identical centers (atoms). Within each subcluster coherent scattering from identical centers may lead to observable phase terms and a geometrical structure factor. Then, using a mean field approximation to describe the interactions between centers we obtain A I ∼ summation k product ke iδ k I A Ik . Second, the independent electron approximation for each center may be obtained by neglecting the correlation between electrons in each center. The probability amplitude for each center is then a product of single electron transition probability amplitudes, a Ik i , i.e. A Ik ≅ product iaik i . Finally, the independent subcluster approximation is introduced by neglecting the interactions between different subclusters in the molecule or cluster. The total probability amplitude then reduces to a simple product of amplitudes for each subcluster, A≅ product IAI . Limitations of this simple approximation are discussed. copyright 1996 American Institute of Physics

  20. Independent sector treatment centres: the first independent evaluation, a Scottish case study.

    Science.gov (United States)

    Pollock, Allyson M; Kirkwood, Graham

    2009-07-01

    The pound5 billion English Independent Sector Treatment Centre (ISTC) programme remains unevaluated because of a lack of published contract data and poor quality data returns. Scotland has a three-year pilot ISTC, the Scottish Regional Treatment Centre (SRTC), the contract for which is now in the public domain. This study aims to conduct an independent evaluation of the performance of the SRTC during the first year of operation. A retrospective analysis of the SRTC comparing activity as reported by hospital episode statistics returned to ISD Scotland with: volume and cost data in the SRTC contract; a 10-month audit carried out by management consultants Price Waterhouse Coopers (PWC); and an internal NHS Tayside performance report. All day-case and inpatient activity at the SRTC from 1 December 2006 to 31 January 2008. Activity and cost. The annual contract was based on patient referrals to the SRTC and not actual treatments. The contract was awarded on the basis of 2624 referrals a year, total value of pound5,667,464. According to ISD data, the SRTC performed 831 procedures (32% of annual contract) in the first 13 months worth pound1,035,603 (18%). PWC's figures report 2200 referrals (84%) to the SRTC at a cost of 2,642,000 (47%) in the first 10 months. Basing the SRTC contract on payments for referrals rather than actual treatment represents a major departure from normal standards of reporting and commissioning and may have resulted in over-payment for referrals for patients who did not receive treatment of up to pound3 million in the first 10 months. The PWC report falls well below the standards one would expect of an independent evaluation and we were unable to validate PWC's analysis and the claim of value for money. If wave-one ISTCs in England perform similarly to the SRTC then as much as pound927 million may have been paid for patients who did not receive treatment. We recommend a moratorium on all ISTC contracts until the contracts have been published and

  1. Central bank independence and conservatism under uncertainty: Substitutes or complements?

    OpenAIRE

    Hefeker, Carsten; Zimmer, Blandine

    2010-01-01

    The paper examines the optimal combination of central bank independence and conservatism in the presence of uncertain central bank preferences. We develop a model of endogenous monetary policy delegation in which government chooses the central bank's degree of inde-pendence and conservatism so as to minimise society's loss function. We find that the optimal combination between independence and conservatism is not necessarily characterised by substitutability. When uncertainty about the centra...

  2. Simulating (log(c) n)-wise Independence in NC

    Science.gov (United States)

    1989-05-01

    independent) distribution. However, Xk (A) = (1x(I))k = Z Z y (i,)...X(ik). iEA ijEAi 2 EA IkEA So Lemma 2.4 applies to show that any k-wise independent...AEA AEAi1EA ikEA So henceforth we want an X such that F(X) >_ E[F(X)]. 2.5 Generating k-Wise Independent Variables It still remains to demonstrate a k

  3. Madness and sanity at the time of Indian independence

    Science.gov (United States)

    Jain, Sanjeev; Murthy, Pratima; Sarin, Alok

    2016-01-01

    The backdrop of the Indian Independence offers glimpses of many ‘metaphors of madness’. In this article, we explore this through a few instances, starting from 1857, around the time of the First War of Independence, to 1947, when India became an independent nation. Such metaphors have their parallels both in historical as well as in contemporary times, where instances of one man's imagination becoming another's concept of irrationality and insanity continue. PMID:28066017

  4. Future independent power generation and implications for instruments and controls

    International Nuclear Information System (INIS)

    Williams, J.H.

    1991-01-01

    This paper reports that the independent power producers market is comprised of cogeneration, small power generation, and independent power production (IPP) segments. Shortfalls in future electric supply are expected to lead to significant growth in this market. The opportunities for instruments and controls will shift from traditional electric utility applications to the independent power market with a more diverse set of needs. Importance will be placed on system reliability, quality of power and increased demand for clean kWh

  5. 17 CFR 240.10A-2 - Auditor independence.

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Auditor independence. 240.10A... Exchange Act of 1934 Reports Under Section 10a § 240.10A-2 Auditor independence. It shall be unlawful for an auditor not to be independent under § 210.2-01(c)(2)(iii)(B), (c)(4), (c)(6), (c)(7), and § 210.2...

  6. Independent regulatory authorities - a comparative study of European energy regulators

    International Nuclear Information System (INIS)

    Sander Johansen, K.; Holm Pedersen, L.; Moll Soerensen, E.

    2004-04-01

    Independent regulatory authorities are widely recommended as part of the institutional design of liberalised energy markets - not least by the European Commission. This report describes and compares the regulatory authorities for energy in the EU. Arguments for regulatory independence are presented and discussed, and an index is developed to measure the degree of conformance to theories of regulatory independence. It is established that the main pattern of variation is that countries, which formerly had strong state-owned companies, have chosen to create regulatory authorities at state level with many institutional safeguards for independence. (au)

  7. A diagrammatic construction of formal E-independent model hamiltonian

    International Nuclear Information System (INIS)

    Kvasnicka, V.

    1977-01-01

    A diagrammatic construction of formal E-independent model interaction (i.e., without second-quantization formalism) is suggested. The construction starts from the quasi-degenerate Brillouin-Wigner perturbation theory, in the framework of which an E-dependent model Hamiltonian is simply constructed. Applying the ''E-removing'' procedure to this E-dependent model Hamiltonian, the E-independent formal model Hamiltonian either Hermitian or non-Hermitian can diagrammatically be easily derived. For the formal E-independent model Hamiltonian the separability theorem is proved, which can be profitably used for a rather ''formalistic ''construction of a many-body E-independent model Hamiltonian

  8. Organization and control of independent work of students

    Directory of Open Access Journals (Sweden)

    Kaydalova L.G.

    2010-01-01

    Full Text Available The theoretical methodical aspects of independent work of students, organization and control, educational methodical providing, forms and types of independent work are examined. Efficiency of independent work is provided high-quality educational literature. The basic forms of control is: current, result and module, examinations, term papers, diploma works, licensed computer-integrated examinations, state attestation. Control can be conducted in a kind: expressquestioning, interview. Control is an information generator for a teacher about motion of independent capture the student of educational by material.

  9. Characterizing speed-independence of high-level designs

    DEFF Research Database (Denmark)

    Kishinevsky, Michael; Staunstrup, Jørgen

    1994-01-01

    This paper characterizes the speed-independence of high-level designs. The characterization is a condition on the design description ensuring that the behavior of the design is independent of the speeds of its components. The behavior of a circuit is modeled as a transition system, that allows data...... types, and internal as well as external non-determinism. This makes it possible to verify the speed-independence of a design without providing an explicit realization of the environment. The verification can be done mechanically. A number of experimental designs have been verified including a speed-independent...

  10. Nuclear Safety Authority independence, progresses to be considered

    International Nuclear Information System (INIS)

    Delzangles, Hubert

    2013-01-01

    The Nuclear Safety Authority is an independent administrative body. Nevertheless, functional and organic independence from operators and government can have different degrees. Having a look on the actual context, where government holds a large part of the main nuclear French operators, independence has to be maximal in order to avoid any conflict of interest that could attempt to nuclear safety. In a global point of view, it is possible to think about the risks or the benefits of the institutionalized cooperation between national regulators on the necessary independence of the Nuclear Safety Authority

  11. Decomposing a Utility Function Based on Discrete Distribution Independence

    DEFF Research Database (Denmark)

    He, Ying; Dyer, James; Butler, John

    2014-01-01

    For two-attribute decision-making problems, the multilinear utility model cannot be applied when the risk aversion on one attribute depends on the level of the other attribute. We propose a family of general preference conditions called nth-degree discrete distribution independence that can...... accommodate a variety of dependence relationships between two attributes. The special case of second-degree discrete distribution independence is equivalent to the utility independence condition. We focus on third-degree discrete distribution independence that leads to a decomposition formula that contains...

  12. Establishing the National Expression in the Work of the Independent Group of Slovenian Artists (The Independents

    Directory of Open Access Journals (Sweden)

    Asta Vrečko

    2015-12-01

    Full Text Available The interwar period was ripe with political crises connected to the national question in the Kingdom of SHS and the Kingdom of Yugoslavia. The relationship between Yugoslav and Slovene identity again became central for the question of national emancipation within an increasing supranational conflict and became the focus of visual arts in the 1930s. After a decade marked by Expressionism and New Objectivity in the thirties, values of moderate modernism and the quest for national expression re-emerged. At the time a new group of artists emerged on the Slovene artistic scene. They were schooled in Zagreb, the cultural centre of the Kingdom of Yugoslavia, where intense polemics regarding national expression in art were taking place. This contribution outlines the search for “our expression” in art as understood by the central protagonists of the art scene in Croatia, Krsto Hegedušić and Ljubo Babić. The latter especially was of central importance to the formation of the young Slovene art, because he was a prolific writer and one of the most important professors at the Academy of Fine Arts in Zagreb. The former Slovenian students, who formed the Independent group of Slovenian artists (Klub neodvisnih slovenskih likovnih umetnikov emerged in the turbulent years before the outbreak of World War II. In art, so they claimed, they were seeking their own, Slovenian national visual expression. In this search they took inspiration from Croatian artists, whose ideas they adapted to the Slovenian situation. At the same time, they legitimised their efforts with references to Slovene impressionists, who were regarded as the founding fathers of Slovene national art. In this way the Independents (Neodvisni sought to highlight the continuity in their search for Slovene national expression in art despite the transformed historical context. They based their national expression in art on a modernist version of Slovene impressionism. They combined this with

  13. Triangle-free graphs whose independence number equals the degree

    DEFF Research Database (Denmark)

    Brandt, Stephan

    2010-01-01

    In a triangle-free graph, the neighbourhood of every vertex is an independent set. We investigate the class S of triangle-free graphs where the neighbourhoods of vertices are maximum independent sets. Such a graph G must be regular of degree d = α (G) and the fractional chromatic number must sati...

  14. Making Boards More Effective: The Issue Of Independence | Ajogwu ...

    African Journals Online (AJOL)

    The authors argue that the independence of the board will be put in jeopardy if the board is made up mainly of executive directors, and if the non-executive directors, where they exist, have significant relationships with parties connected to the firm. Other sources of threat to the independence of the board are the combination ...

  15. Independent companies in the North Sea - exploration and operations opportunities

    International Nuclear Information System (INIS)

    Greentree, C.

    1992-01-01

    The North Sea was the launching pad for many independent oil companies, particularly through exploration success in the UK and the Netherlands. Norway has an excellent history of oil exploration but, for the independents, the onerous tax regime, long lead times, and terms of trade are simply not conducive to the higher rate of return demanded by shareholders of independent E and P companies in exchange for shouldering the heavy burden of risk. The UK in particular has pursued imaginative licensing, tax and legislative policies which have allowed the independents an opportunity to participate and grow. The attraction of the UK is clearly reflected by the constant arrival of new entrants, even at this stage of maturity. This was demonstrated in the recent round of license awards. Such has been the success of the independents in the UK that, beginning with virtually nothing, they now hold a net 28% of the UK North Sea acreage, and a net 25% of its oil reserves. Equally, the independents play an important role in ensuring the comprehensive exploration of the offshore areas. Because of size and significance, a prime objective of the independents will remain the early evaluation, through drilling, and development of offshore interests to generate a financial return. This paper addresses the question of how independent companies can expand in the North Sea when the size and quality of new range acreage available through new license awards is reducing. (author)

  16. Anomalously temperature-independent birefringence in biaxial optical crystals

    International Nuclear Information System (INIS)

    Grechin, Sergei G; Dmitriev, Valentin G; Dyakov, Vladimir A; Pryalkin, Vladimir I

    2000-01-01

    Temperature-independent birefringence in a biaxial crystal was predicted theoretically and observed experimentally for the first time. The width of the plot against temperature (the range corresponding to the temperature independence of the birefringence) at a fundamental radiation wavelength of 632.8 nm in a KTP crystal 5.9 mm long was more than 160 0 C. (letters to the editor)

  17. The Trade Off Between Central Bank Independence and Conservativeness

    NARCIS (Netherlands)

    Eijffinger, S.C.W.; Hoeberichts, M.M.

    1996-01-01

    This paper introduces a parameter for central bank independence in a monetary policy game with a conservative central banker.It tries to explain the optimal degree of central bank independence and conservativeness by four economic and political determinants, both theoretically and empirically.There

  18. Production and use of independent media: road to government accountability?

    NARCIS (Netherlands)

    A. Macedo de Jesus (Anderson); I.L. van Staveren (Iris)

    2014-01-01

    markdownabstract__Abstract__ This study addresses the question to what extent independent media contributes to government accountability, in particular the social accountability of governments in service delivery. It does so by analysing the effect of the production and use of independent media

  19. Testing independence of fragment lengths within VNTR loci

    Energy Technology Data Exchange (ETDEWEB)

    Geisser, S. (Univ. of Minnesota, Minneapolis, MN (United States)); Johnson, W. (Univ. of California, Davis, CA (United States))

    1993-11-01

    Methods that were devised to test independence of the bivariate fragment lengths obtained from VNTR loci are applied to several population databases. It is shown that for many of the probes independence (Hardy-Weinberg equilibrium) cannot be sustained. 3 refs., 3 tabs.

  20. Transplanted human pancreatic islets after long-term insulin independence

    DEFF Research Database (Denmark)

    Muller, Y D; Gupta, Shashank; Morel, P

    2013-01-01

    Long-term insulin independence after islets of Langerhans transplantation is rarely achieved. The aims of this study were to identify the histological and immunological features of islets transplanted in a type 1 diabetic patient who died of a cerebral hemorrhage after >13 years insulin independe...

  1. The Internet and the Independence of Individuals with Disabilities.

    Science.gov (United States)

    Grimaldi, Caroline; Goette, Tanya

    1999-01-01

    This study examined the role of the Internet and its usage on the level of perceived independence among people with physical disabilities. Discusses independence, perceived control, psychological self-reliance, adaptive technology, hypotheses tested, and future directions. A copy of one of the questionnaires used is appended. (Author/LRW)

  2. Reconfiguring Independent Sets in Claw-Free Graphs

    NARCIS (Netherlands)

    Bonsma, P.S.; Kamiński, Marcin; Wrochna, Marcin; Ravi, R.; Gørtz, Inge Li

    We present a polynomial-time algorithm that, given two independent sets in a claw-free graph G, decides whether one can be transformed into the other by a sequence of elementary steps. Each elementary step is to remove a vertex v from the current independent set S and to add a new vertex w (not in

  3. Tomato sorting using independent component analysis on spectral images

    NARCIS (Netherlands)

    Polder, G.; Heijden, van der G.W.A.M.; Young, I.T.

    2003-01-01

    Independent Component Analysis is one of the most widely used methods for blind source separation. In this paper we use this technique to estimate the most important compounds which play a role in the ripening of tomatoes. Spectral images of tomatoes were analyzed. Two main independent components

  4. The Financial Resilience of Independent Colleges and Universities

    Science.gov (United States)

    Chessman, Hollie M.; Hartley, Harold V., III; Williams, Michael

    2017-01-01

    This report explores the financial resilience of independent colleges and universities through an analysis of 14 years (fiscal years 2001-2014) of financial data from 559 private nondoctoral institutions. Through analysis of financial performance in several domains, the data reveal that the majority of independent baccalaureate and master's-level…

  5. Some Results on the Independence Polynomial of Unicyclic Graphs

    Directory of Open Access Journals (Sweden)

    Oboudi Mohammad Reza

    2018-05-01

    Full Text Available Let G be a simple graph on n vertices. An independent set in a graph is a set of pairwise non-adjacent vertices. The independence polynomial of G is the polynomial I(G,x=∑k=0ns(G,kxk$I(G,x = \\sum\

  6. The number of independent sets in unicyclic graphs

    DEFF Research Database (Denmark)

    Pedersen, Anders Sune; Vestergaard, Preben Dahl

      In this paper, we determine upper and lower bounds for the number of independent sets in a unicyclic graph in terms of its order. This gives an upper bound for the number of independent sets in a connected graph which contains at least one cycle. We also determine the upper bound for the number...

  7. Considerations on establishment of an independent TSO in Indonesia

    International Nuclear Information System (INIS)

    Huda, Kholrul

    2010-01-01

    To strengthen the national safety infrastructure is absolutely needed for countries those are embarking to nuclear power. Establishment of an independent technical support organization (TSO) is one of the important steps in strengthening the safety infrastructure. TSO is dedicated to provide independent scientific and technical advices to the regulatory body in conducting regulatory process effectively. Indonesia is one of the countries who have already had a function o fTSO within its Regulatory Body's organization ('internal TSO'). So, the independence of TSO is remarkably questioned. In this case, an independent TSO could be achieved by excluding the internal TSO or strengthening, its legal position in a different organisation. In addition, since the TSO might also be needed by the executing body, a hybrid organization of TSO with dual-function is being considered. Present paper provides some considerations regarding the establishment of independent TSO in Indonesia. (author)

  8. Does Board Independence Matter? Evidence from New Zealand

    Directory of Open Access Journals (Sweden)

    Hardjo Koerniadi

    2012-06-01

    Full Text Available This paper examines the effects of the presence of independent directors on firm value using both market-based performance measures (Tobin’s Q ratio and EVA and accounting-based ratios (ROA and ROE. We find that, instead of adding value, independent directors in NewZealand negatively affect firm value. We also find that, consistent with stewardship theory,independent directors have a positive effect on firm value only when they are in the minority.These findings are important given the increasing trend toward independence in corporate boards around the globe and suggest that board independence may not generally be suitable for countries where managers are considered as active partners along with other stakeholders in companies.

  9. Practical device-independent quantum cryptography via entropy accumulation.

    Science.gov (United States)

    Arnon-Friedman, Rotem; Dupuis, Frédéric; Fawzi, Omar; Renner, Renato; Vidick, Thomas

    2018-01-31

    Device-independent cryptography goes beyond conventional quantum cryptography by providing security that holds independently of the quality of the underlying physical devices. Device-independent protocols are based on the quantum phenomena of non-locality and the violation of Bell inequalities. This high level of security could so far only be established under conditions which are not achievable experimentally. Here we present a property of entropy, termed "entropy accumulation", which asserts that the total amount of entropy of a large system is the sum of its parts. We use this property to prove the security of cryptographic protocols, including device-independent quantum key distribution, while achieving essentially optimal parameters. Recent experimental progress, which enabled loophole-free Bell tests, suggests that the achieved parameters are technologically accessible. Our work hence provides the theoretical groundwork for experimental demonstrations of device-independent cryptography.

  10. Opportunities await U.S. independents willing to change

    International Nuclear Information System (INIS)

    Henry, J.C.

    1996-01-01

    Major trends are changing the ways independent oil and gas producers do business. Companies that recognize these major trends and take advantage of them will prosper. The ones that don't change will wither on the vine. The trends reflect the advanced stage that the US has reached in the production cycle of its petroleum resource. Mature production means that: major oil companies have sold off many of their low-return properties and shifted their financial resources and human resources to core properties; major oil companies are shifting assets from the US to other producing countries at earlier stages of production; the operating divisions of major oil companies in the US are becoming more like independents; independents are filling the void left by major oil companies; and these independents are either exploitationists or depletionists. These trends are changing not just business practices but the positions independent producers take on long-running political issues. These trends are discussed

  11. Financial Independence of Central Bank through the Balance Sheet Prism

    Directory of Open Access Journals (Sweden)

    Ivanović Valentina

    2014-05-01

    Full Text Available The main reason for central bank independence lies in the fact that it is necessary to clearly distinguish spending money from the ability of making money. Independence of central banks is now a characteristic of almost all developed and highly industrialized countries. In this respect, it represents an essential part of the overall economic reality of these countries. Over the past decade or somewhat earlier, the issue of importance of central bank independence has been raised in developing countries, making the institutional, functional, personal and financial independence of central banks current topics for consideration. The key reason for the growing attention to financial independence of central banks is due to the effects of the global financial crisis on their balance sheets and therefore the challenges related to achieving the basic goals of the functioning of central banks - financial stability and price stability.

  12. Independent component analysis for automatic note extraction from musical trills

    Science.gov (United States)

    Brown, Judith C.; Smaragdis, Paris

    2004-05-01

    The method of principal component analysis, which is based on second-order statistics (or linear independence), has long been used for redundancy reduction of audio data. The more recent technique of independent component analysis, enforcing much stricter statistical criteria based on higher-order statistical independence, is introduced and shown to be far superior in separating independent musical sources. This theory has been applied to piano trills and a database of trill rates was assembled from experiments with a computer-driven piano, recordings of a professional pianist, and commercially available compact disks. The method of independent component analysis has thus been shown to be an outstanding, effective means of automatically extracting interesting musical information from a sea of redundant data.

  13. Reclaiming Independence: American Independent Cinema Distribution and Exhibition Practices beyond Indiewood

    Directory of Open Access Journals (Sweden)

    Yannis Tzioumakis

    2012-06-01

    , while two years later the once mighty Miramax was sold by Disney. This consolidation created a sector that is now controlled by a handful of major conglomerate subsidiaries and a few diversified stand-alone companies. These companies have been investing increasingly in commercial properties, with films like Juno (2007 and Sideways (2006 achieving commercial success almost on a par with studio pictures and provoking reactions from critics who have questioned their independent status.While “indie” film seems to be on a convergence course with studio filmmaking (and marketing, the “lower end” of the independent spectrum has seen developments that seem to be driven by models that increasingly bypass theatrical distribution and exhibition. Such models aim to link the film producer with an audience who consume films at home, and are characterised by practices such as the sale of DVDs from the filmmakers’ own websites to a substantial clientele; and an extensive and innovative use of social networking media. The low cost of these practices allows some of these films to achieve profitability, which enables their filmmakers to continue working without compromises. In this respect, the essay argues that despite the increasing institutionalisation of American independent and the cooptation of “indie” film from the Hollywood conglomerates in recent years, the introduction of new film business models at the low end of the sector has once again allowed independent cinema to regenerate and to continue to provide an alternative to Hollywood.

  14. Device-independent characterizations of a shared quantum state independent of any Bell inequalities

    Science.gov (United States)

    Wei, Zhaohui; Sikora, Jamie

    2017-03-01

    In a Bell experiment two parties share a quantum state and perform local measurements on their subsystems separately, and the statistics of the measurement outcomes are recorded as a Bell correlation. For any Bell correlation, it turns out that a quantum state with minimal size that is able to produce this correlation can always be pure. In this work, we first exhibit two device-independent characterizations for the pure state that Alice and Bob share using only the correlation data. Specifically, we give two conditions that the Schmidt coefficients must satisfy, which can be tight, and have various applications in quantum tasks. First, one of the characterizations allows us to bound the entanglement between Alice and Bob using Renyi entropies and also to bound the underlying Hilbert space dimension. Second, when the Hilbert space dimension bound is tight, the shared pure quantum state has to be maximally entangled. Third, the second characterization gives a sufficient condition that a Bell correlation cannot be generated by particular quantum states. We also show that our results can be generalized to the case of shared mixed states.

  15. Associations between children’s independent mobility and physical activity

    Science.gov (United States)

    2014-01-01

    Background Independent mobility describes the freedom of children to travel and play in public spaces without adult supervision. The potential benefits for children are significant such as social interactions with peers, spatial and traffic safety skills and increased physical activity. Yet, the health benefits of independent mobility, particularly on physical activity accumulation, are largely unexplored. This study aimed to investigate associations of children’s independent mobility with light, moderate-to-vigorous, and total physical activity accumulation. Methods In 2011 - 2012, 375 Australian children aged 8-13 years (62% girls) were recruited into a cross-sectional study. Children’s independent mobility (i.e. independent travel to school and non-school destinations, independent outdoor play) and socio-demographics were assessed through child and parent surveys. Physical activity intensity was measured objectively through an Actiheart monitor worn on four consecutive days. Associations between independent mobility and physical activity variables were analysed using generalized linear models, accounting for clustered sampling, Actiheart wear time, socio-demographics, and assessing interactions by sex. Results Independent travel (walking, cycling, public transport) to school and non-school destinations were not associated with light, moderate-to-vigorous and total physical activity. However, sub-analyses revealed a positive association between independent walking and cycling (excluding public transport) to school and total physical but only in boys (b = 36.03, p physical activity (b = 29.76, p physical activity. When assessing differences by sex, the observed significant associations of independent outdoor play with light and total physical activity remained in girls but not in boys. All other associations showed no significant differences by sex. Conclusions Independent outdoor play may boost children’s daily physical activity levels

  16. Independent versus non-independent outside directors in European companies: Who has a say on CEO compensation?

    Directory of Open Access Journals (Sweden)

    Pablo de Andrés

    2017-04-01

    Full Text Available Our study reveals how two separate dimensions of board composition—the proportion of independent directors and of non-independent directors—influence CEO compensation in Western European firms. Controlling for the simultaneous determination of CEO pay structure and board design, we find that firms with a higher proportion of non-independent outsiders on their boards pay less direct compensation (salary + bonus and less equity-linked compensation to their CEOs. By contrast, CEOs working for firms with more independent boards receive more equity based-pay. When we control for the fact that equity linked is not granted systematically in Europe we find that firms with more independent directors on the board tend to grant equity-linked compensation more often than firms with more non independent outside directors. Our results challenge the commonly accepted view of independent directors as safeguards of shareholder value, uncovering the relevance of non-independent outsiders for pay moderation and incentives.

  17. The role of independent inspection in verification activities

    International Nuclear Information System (INIS)

    Fuerste, W.

    1982-01-01

    Independent inspection has its origin in the early Middle Ages, when kings prescribed to textile manufacturers a quality control by authorized inspectors. Independent inspection became more important with respect to the safety of workers in the industrial era beginning in the 18th century, when the high-pressure steam engines were introduced and many accidents and explosions of steam boilers occurred. Nowadays, independent inspection is of utmost importance, because the safety of the public is endangered by industrial plants located near highly populated areas. To better understand the role of independent inspection, the paper reviews its historical development in Europe from the Middle Ages to the 20th century. Most of the independent inspection associations in European countries were established after the second half of the 19th century and began with the surveillance of steam boilers. Nowadays, organizations like the TUEVs (Technical Inspection Agencies) in the Federal Republic of Germany perform expertise and inspection on behalf of the government in various fields of industrial safety. To show how independent inspection is involved in quality assurance, the methods practised in the United States of America and the Federal Republic of Germany are compared and future trends discussed. For developing countries starting with nuclear energy, it is important to consider the information and recommendations regarding independent inspection and its regulation as laid down in a number of publications in the IAEA NUSS Programme. (author)

  18. Signal-dependent independent component analysis by tunable mother wavelets

    International Nuclear Information System (INIS)

    Seo, Kyung Ho

    2006-02-01

    The objective of this study is to improve the standard independent component analysis when applied to real-world signals. Independent component analysis starts from the assumption that signals from different physical sources are statistically independent. But real-world signals such as EEG, ECG, MEG, and fMRI signals are not statistically independent perfectly. By definition, standard independent component analysis algorithms are not able to estimate statistically dependent sources, that is, when the assumption of independence does not hold. Therefore before independent component analysis, some preprocessing stage is needed. This paper started from simple intuition that wavelet transformed source signals by 'well-tuned' mother wavelet will be simplified sufficiently, and then the source separation will show better results. By the correlation coefficient method, the tuning process between source signal and tunable mother wavelet was executed. Gamma component of raw EEG signal was set to target signal, and wavelet transform was executed by tuned mother wavelet and standard mother wavelets. Simulation results by these wavelets was shown

  19. Developing an Independence State: Some Insights from Qalam Publication

    Directory of Open Access Journals (Sweden)

    Norziati Mohd Rosman

    2017-03-01

    Full Text Available This article is to identify a few concepts on independence and proposed a necessary approach in developing an identity of the country by analysing articles written in Qalam periodicals by three figures, Edrus, Dr Burhanuddin al-Helmy and Muhammad Isa Anshary. Qalam is a socio-politics periodical in Jawi script published in Singapore in 1950 until 1969. By analysing the writings, it is believed that proclamation of Indonesian independence in 1945 inspired to the development of Malaysia as a sovereign country and influenced readers in Malaya, Singapore and Brunei in which their countries were still struggling for independence.

  20. Regulatory challenges faced first Indonesia NPPs by independent TSOs

    International Nuclear Information System (INIS)

    Sri Budi Utami

    2010-01-01

    Technical and scientific support organizations (TSOs) dedicated to supporting national regulatory authorities. At present BAPETEN has internal TSOs. Pertaining to the regulatory control of nuclear safety, security, and safeguards for nuclear power plants (NPPs), independent TSOs providing support to the safety regulatory bodies are facing a number of technical challenges to ensuring the safety of NPPs. It is essential that BAPETEN need independent TSOs in order to warrant a sufficient level of safety, security and non proliferation in building and operating of first NPP. It is essential that BAPETEN need independent TSOs in order to warrant a sufficient level of safety, security and non proliferation in building and operating of first NPPs. (author)

  1. Explaining the judicial independence of international courts: a comparative analysis

    DEFF Research Database (Denmark)

    Beach, Derek

    What factors allow some international courts (ICs) to rule against the express preferences of powerful member states, whereas others routinely defer to governments? While judicial independence is not the only factor explaining the strength of a given international institution, it is a necessary...... condition. The paper first develops three sets of competing explanatory variables that potentially can explain variations in the judicial independence of ICs. The causal effects of these explanatory variables upon variance in judicial independence are investigated in a comparative analysis of the ACJ, ECJ...

  2. Towards Device-Independent Information Processing on General Quantum Networks

    Science.gov (United States)

    Lee, Ciarán M.; Hoban, Matty J.

    2018-01-01

    The violation of certain Bell inequalities allows for device-independent information processing secure against nonsignaling eavesdroppers. However, this only holds for the Bell network, in which two or more agents perform local measurements on a single shared source of entanglement. To overcome the practical constraints that entangled systems can only be transmitted over relatively short distances, large-scale multisource networks have been employed. Do there exist analogs of Bell inequalities for such networks, whose violation is a resource for device independence? In this Letter, the violation of recently derived polynomial Bell inequalities will be shown to allow for device independence on multisource networks, secure against nonsignaling eavesdroppers.

  3. Solving the oil independence problem: Is it possible?

    International Nuclear Information System (INIS)

    Sovacool, Benjamin K.

    2007-01-01

    As currently discussed in political circles, oil independence is unattainable - lacking coherent meaning and wedding policymakers to the notion that they can never accomplish it. Contrary to this thinking, more than a dozen different sets of technologies and practices could increase domestic supply and reduce demand for oil to the point of making the US functionally independent from oil price shocks. However, achieving this goal demands concerted action to expand and diversify conventional domestic oil supplies, reduce overall demand in the transportation and buildings sector, and continue to develop alternative fuels. If policymakers undertook such actions today, the US could become oil independent by 2030. (author)

  4. Multiple independent identification decisions: a method of calibrating eyewitness identifications.

    Science.gov (United States)

    Pryke, Sean; Lindsay, R C L; Dysart, Jennifer E; Dupuis, Paul

    2004-02-01

    Two experiments (N = 147 and N = 90) explored the use of multiple independent lineups to identify a target seen live. In Experiment 1, simultaneous face, body, and sequential voice lineups were used. In Experiment 2, sequential face, body, voice, and clothing lineups were used. Both studies demonstrated that multiple identifications (by the same witness) from independent lineups of different features are highly diagnostic of suspect guilt (G. L. Wells & R. C. L. Lindsay, 1980). The number of suspect and foil selections from multiple independent lineups provides a powerful method of calibrating the accuracy of eyewitness identification. Implications for use of current methods are discussed. ((c) 2004 APA, all rights reserved)

  5. Tenneco raises $75 million for independents' E and P

    International Nuclear Information System (INIS)

    Land, R.

    1992-01-01

    Tenneco Gas's ventures group, Houston, has raised $75 million to invest in gas exploration and production by independent operations on the U.S. Gulf Coast. Institutional investors committed $50 million to the fund and a group of industrial investors $25 million. Tenneco the the fund will expand to accommodate additional investors through this year. This paper reports that the company's ventures group is evaluating acquisition and drilling opportunities with independents. Ventures group capital will be invested in independent exploratory, development, and producing properties

  6. U.S. independent operators step up exploration, development abroad

    International Nuclear Information System (INIS)

    Koen, A.D.

    1996-01-01

    This paper reviews the new trend of independent oil and gas operation expenditures in overseas development. It compares recent trends in production, production revenues, and exploration and development expenditures in both the US and non-US markets. It identifies numerous development projects going on in China, Columbia, Australia, Algeria, and others. It documents the production revenues from the overseas fields compared to the returns on US production. It also documents many of the advantages that the independents have over the major companies to obtain a competitive edge on developments in these regions. A historical perspective is also given which tracks the gradual changes of the way which independents operate

  7. INDEPENDENCE OF JUDGES IN THE IMPLEMENTATION POWERS OF JUSTICE

    OpenAIRE

    Nurul Qamar

    2015-01-01

    This article aims to explore the independence of the judiciary as an important pillar of a rule of law. Independence of the judiciary is a necessary condition for maintaining the rule of law, only constitutional law has legitimacy that must be upheld and the court should have the ability to perform a task in deciding the law. The independence of judges to examine, prosecute and deciding have guaranteed in the Constitution of the Republic of Indonesia Year 1945 and Act No. 48 of 2009 on Judic...

  8. On the path independence conditions for discrete-continuous demand

    DEFF Research Database (Denmark)

    Batley, Richard; Ibáñez Rivas, Juan Nicolás

    2013-01-01

    We consider the manner in which the well-established path independence conditions apply to Small and Rosen's (1981) problem of discrete-continuous demand, focussing especially upon the restricted case of discrete choice (probabilistic) demand. We note that the consumer surplus measure promoted...... by Small and Rosen, which is specific to the probabilistic demand, imposes path independence to price changes a priori. We find that path independence to income changes can further be imposed provided a numeraire good is available in the consumption set. We show that, for practical purposes, Mc...

  9. Board Independence and Corporate Social Responsibility (CSR Reporting in Malaysia

    Directory of Open Access Journals (Sweden)

    Nurulyasmin Binti Ju Ahmad

    2017-06-01

    Full Text Available This study aims to examine the influence of board independence on corporate social responsibility (CSR reporting by publicly listed companies in Malaysia. Content analysis was used to determine the extent of CSR reporting. A reporting index consisting of 51 items was developed based on six themes: General, Community, Environment, Human Resources, Marketplace and Other. An Ordinary Least Square (OLS regression was used to examine the relationship between board independence and firm CSR reporting. The results indicate that the association between board independence and company CSR reporting is industry specific. Overall, the empirical evidence partially supports agency theory.

  10. Independent verification in operations at nuclear power plants

    International Nuclear Information System (INIS)

    Donderi, D.C.; Smiley, A.; Ostry, D.J.; Moray, N.P.

    1995-09-01

    A critical review of approaches to independent verification in operations used in nuclear power plant quality assurance programs in other countries, was conducted for this study. This report identifies the uses of independent verification and provides an assessment of the effectiveness of the various approaches. The findings indicate that at Canadian nuclear power plants as much, if not more, independent verification is performed than at power plants in the other countries included in the study. Additional requirements in this area are not proposed for Canadian stations. (author)

  11. Non-audit services and auditor independence: Norwegian evidence

    DEFF Research Database (Denmark)

    Zhang, Yu (Elli); Hay, David; Holm, Claus

    2016-01-01

    We examine the effect on auditor independence of auditors providing non-audit services in the Norwegian audit market. We report the results of three tests of independence of mind and one test of independence in appearance. These tests find that there is a positive relationship between audit fees......-audit services and the frequency with which auditors issue modified audit opinions. There is no association between non-audit services and audit tenure. Finally, we examine the relationship between unexpected or excess non-audit fees and cost of capital. There is no relationship. Our findings fail to find any...

  12. Guidelines for the marketing of independent schools in South Africa

    Directory of Open Access Journals (Sweden)

    Reaan Immelman

    2015-02-01

    Full Text Available Objective: The primary objective of the study is to recommend marketing guidelines for independent primary schools, with the focus on product and people in the marketing mix. This objective was achieved by identifying choice factors influencing parents’ selection of independent primary schools, identifying the most important choice factors and demographic differences regarding the importance parents attached to these factors. Problem investigated: Some independent schools in South Africa find it difficult to market themselves effectively as a result of a lack of information pertaining to the choice factors identified by parents when selecting independent primary schools. A comprehensive set of choice factors will provide a more accurate picture of the criteria parents perceive as important in independent school selection. Methodology: The methodological approach followed was exploratory and quantitative in nature. The sample consisted of 669 respondents from 30 independent schools in Gauteng in South Africa. A structured questionnaire, with a five-point Likert scale, was fielded to gather the data. The descriptive and factor analysis approaches were used to analyse the results. Findings and implications: The main finding is that a total of 29 different choice factors were identified that parents perceive as important when selecting an independent primary school. The most important factor for parents when making a choice is the small size of the classes, followed by the religious ethos of the school as well as qualified and committed educators. This indicates that parents have a comprehensive set of choice factors and implies that a better understanding of these factors by independent schools may assist them to focus their marketing efforts more optimally in order to attract new learners. Originality and value of the research: Very little research exists with specific reference to independent school marketing in South Africa

  13. Retrograde transport of protein toxins through the Golgi apparatus

    DEFF Research Database (Denmark)

    Sandvig, Kirsten; Skotland, Tore; van Deurs, Bo

    2013-01-01

    at the cell surface, and they are endocytosed both by clathrin-dependent and clathrin-independent mechanisms. Sorting to the Golgi and retrograde transport to the endoplasmic reticulum (ER) are common to these toxins, but the exact mechanisms turn out to be toxin and cell-type dependent. In the ER...

  14. The comparative role of independent and intervening variables on ...

    African Journals Online (AJOL)

    The comparative role of independent and intervening variables on ... forced this study to investigate variables that are most important in determining the adoption behaviour. A cross sectional research design was used to collect data from 113 ...

  15. Web Services for Telegeriatric and Independent Living of the Elderly ...

    African Journals Online (AJOL)

    pc

    2018-03-05

    Mar 5, 2018 ... models. The platform design follows a patient centric philosophy along with the ... aging population in the World). ... independent living environment for older people at home ...... impact scope. .... Configuring a Trusted Cloud.

  16. Platform-independent method for computer aided schematic drawings

    Science.gov (United States)

    Vell, Jeffrey L [Slingerlands, NY; Siganporia, Darius M [Clifton Park, NY; Levy, Arthur J [Fort Lauderdale, FL

    2012-02-14

    A CAD/CAM method is disclosed for a computer system to capture and interchange schematic drawing and associated design information. The schematic drawing and design information are stored in an extensible, platform-independent format.

  17. Web Services for Telegeriatric and Independent Living of the Elderly ...

    African Journals Online (AJOL)

    pc

    2018-03-05

    Mar 5, 2018 ... “Smart Home” technologies can help foster a safe and independent living ..... with care services and other relevant organizational bodies). To support ..... National Center for Injury Prevention and Control. Web–based injury ...

  18. Southeast Fishery-Independent Survey (PC1603, ME70)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The NOAA ship Pisces departed Morehead city on 3 July 2016 for a Southeast Fishery-Independent Survey (SEFIS) research cruise in continental shelf and shelf-break...

  19. Southeast Fishery-Independent Survey (PC1402, ME70)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Southeast Fishery-Independent Survey (SEFIS) was created by the National Marine Fisheries Service in 2010 and operates out of the NOAA Beaufort Laboratory. The...

  20. A representation independent propagator. Pt. 1. Compact Lie groups

    International Nuclear Information System (INIS)

    Tome, W.A.

    1995-01-01

    Conventional path integral expressions for propagators are representation dependent. Rather than having to adapt each propagator to the representation in question, it is shown that for compact Lie groups it is possible to introduce a propagator that is representation independent. For a given set of kinematical variables this propagator is a single function independent of any particular choice of fiducial vector, which monetheless, correctly propagates each element of the coherent state representation associated with these kinematical variables. Although the configuration space is in general curved, nevertheless the lattice phase-space path integral for the representation independent propagator has the form appropriate to flat space. To illustrate the general theory a representation independent propagator is explicitly constructed for the Lie group SU(2). (orig.)

  1. Halo-independent methods for inelastic dark matter scattering

    International Nuclear Information System (INIS)

    Bozorgnia, Nassim; Schwetz, Thomas; Herrero-Garcia, Juan; Zupan, Jure

    2013-01-01

    We present halo-independent methods to analyze the results of dark matter direct detection experiments assuming inelastic scattering. We focus on the annual modulation signal reported by DAMA/LIBRA and present three different halo-independent tests. First, we compare it to the upper limit on the unmodulated rate from XENON100 using (a) the trivial requirement that the amplitude of the annual modulation has to be smaller than the bound on the unmodulated rate, and (b) a bound on the annual modulation amplitude based on an expansion in the Earth's velocity. The third test uses the special predictions of the signal shape for inelastic scattering and allows for an internal consistency check of the data without referring to any astrophysics. We conclude that a strong conflict between DAMA/LIBRA and XENON100 in the framework of spin-independent inelastic scattering can be established independently of the local properties of the dark matter halo

  2. Device-Independent Certification of a Nonprojective Qubit Measurement

    Science.gov (United States)

    Gómez, Esteban S.; Gómez, Santiago; González, Pablo; Cañas, Gustavo; Barra, Johanna F.; Delgado, Aldo; Xavier, Guilherme B.; Cabello, Adán; Kleinmann, Matthias; Vértesi, Tamás; Lima, Gustavo

    2016-12-01

    Quantum measurements on a two-level system can have more than two independent outcomes, and in this case, the measurement cannot be projective. Measurements of this general type are essential to an operational approach to quantum theory, but so far, the nonprojective character of a measurement can only be verified experimentally by already assuming a specific quantum model of parts of the experimental setup. Here, we overcome this restriction by using a device-independent approach. In an experiment on pairs of polarization-entangled photonic qubits we violate by more than 8 standard deviations a Bell-like correlation inequality that is valid for all sets of two-outcome measurements in any dimension. We combine this with a device-independent verification that the system is best described by two qubits, which therefore constitutes the first device-independent certification of a nonprojective quantum measurement.

  3. Constraints on effective interactions imposed by antisymmetry and charge independence

    Energy Technology Data Exchange (ETDEWEB)

    Stringari, S [Trento Univ. (Italy). Dipartimento di Matematica e Fisica; Brink, D M [Oxford Univ. (UK). Dept. of Theoretical Physics

    1978-07-24

    Restrictions on the form of the energy functional following antisymmetry and charge independence have been investigated for a Hartree-Fock theory based on effective interactions. These restrictions impose severe constraints on density dependent effective interactions.

  4. Biologic consequences of Stat1-independent IFN signaling

    Science.gov (United States)

    Gil, M. Pilar; Bohn, Erwin; O'Guin, Andrew K.; Ramana, Chilakamarti V.; Levine, Beth; Stark, George R.; Virgin, Herbert W.; Schreiber, Robert D.

    2001-01-01

    Although Stat1 is required for many IFN-dependent responses, recent work has shown that IFNγ functions independently of Stat1 to affect the growth of tumor cells or immortalized fibroblasts. We now demonstrate that both IFNγ and IFNα/β regulate proliferative responses in cells of the mononuclear phagocyte lineage derived from Stat1-null mice. Using both representational difference analysis and gene arrays, we show that IFNγ exerts its Stat1-independent actions on mononuclear phagocytes by regulating the expression of many genes. This result was confirmed by monitoring changes in expression and function of the corresponding gene products. Regulation of the expression of these genes requires the IFNγ receptor and Jak1. The physiologic relevance of IFN-dependent, Stat1-independent signaling was demonstrated by monitoring antiviral responses in Stat1-null mice. Thus, the IFN receptors engage alternative Stat1-independent signaling pathways that have important physiological consequences. PMID:11390995

  5. 38 CFR 21.146 - Independent instructor course.

    Science.gov (United States)

    2010-07-01

    .... Chapter 31 Special Rehabilitation Services § 21.146 Independent instructor course. (a) Definition. An... the customary channels leading to employment may not be readily available to a veteran requiring an...

  6. Verification of Linear (In)Dependence in Finite Precision Arithmetic

    Czech Academy of Sciences Publication Activity Database

    Rohn, Jiří

    2014-01-01

    Roč. 8, č. 3-4 (2014), s. 323-328 ISSN 1661-8289 Institutional support: RVO:67985807 Keywords : linear dependence * linear independence * pseudoinverse matrix * finite precision arithmetic * verification * MATLAB file Subject RIV: BA - General Mathematics

  7. Contributory factors for the functional independence of oldest old

    Directory of Open Access Journals (Sweden)

    Dâmarys Kohlbeck de Melo Neu Ribeiro

    2015-02-01

    Full Text Available OBJECTIVE To investigate the socioeconomic and clinical factors that contribute to the functional independence of the oldest old of a community. METHOD Cross-sectional quantitative study whose sample consisted of 214 elderly people registered in Basic Health Units. Data were collected through structured interviews and application of the Functional Independence Measure. We used descriptive statistics, and for association of the variables we used the Student t-test, ANOVA and Tukey's test for multiple comparisons. RESULTS The significant variables that contributed to the functional independence were remaining economically active, practicing physical and leisure activities, having a social life, eating fruits, vegetables and meat. The orientation to conduct these practices reduces the demand for care and help needed in everyday activities. CONCLUSION Maintaining independence is primordial to delay disability and presents itself as an excellent field of work for nursing.

  8. Independent component analysis in non-hypothesis driven metabolomics

    DEFF Research Database (Denmark)

    Li, Xiang; Hansen, Jakob; Zhao, Xinjie

    2012-01-01

    In a non-hypothesis driven metabolomics approach plasma samples collected at six different time points (before, during and after an exercise bout) were analyzed by gas chromatography-time of flight mass spectrometry (GC-TOF MS). Since independent component analysis (ICA) does not need a priori...... information on the investigated process and moreover can separate statistically independent source signals with non-Gaussian distribution, we aimed to elucidate the analytical power of ICA for the metabolic pattern analysis and the identification of key metabolites in this exercise study. A novel approach...... based on descriptive statistics was established to optimize ICA model. In the GC-TOF MS data set the number of principal components after whitening and the number of independent components of ICA were optimized and systematically selected by descriptive statistics. The elucidated dominating independent...

  9. The impact of employment statutes on independent contract workers

    International Nuclear Information System (INIS)

    Molnar, L.F.

    1999-01-01

    The minimum statutory entitlements that apply to employees and independent contractors engaged in Alberta's petroleum industry were reviewed. The importance of employers being aware of the potential applications of these statutes to its independent contractors was emphasized. The employment relationship between independent contractors and employers are regulated by the Employment Standards Code and the Human Rights, Citizenship and Multiculturalism Act. The paper also described the obligations that the Occupational Health and Safety Act and the Workers' Compensation Act impose on both employers and independent contractors. This presentation also listed the criteria used in determining if a person is performing a contract of employment or a contract for service. An employee/non-employee questionnaire was also included

  10. Southeast Fishery-Independent Survey (PC1304, ME70)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Southeast Fishery-Independent Survey (SEFIS) was created by the National Marine Fisheries Service in 2010 and operates out of the NOAA Beaufort Laboratory. The...

  11. Positive Disposition in the Prediction of Strategic Independence among Millennials

    Directory of Open Access Journals (Sweden)

    Robert Konopaske

    2017-11-01

    Full Text Available Research on the dispositional traits of Millennials (born in 1980–2000 finds that this generation, compared to earlier generations, tends to be more narcissistic, hold themselves in higher regard and feel more entitled to rewards. The purpose of this intragenerational study is to counter balance extant research by exploring how the positive dispositional traits of proactive personality, core self-evaluation, grit and self-control predict strategic independence in a sample of 311 young adults. Strategic independence is a composite variable measuring a person’s tendency to make plans and achieve long-term goals. A confirmatory factor analysis and hierarchical regression found evidence of discriminant validity across the scales and that three of the four independent variables were statistically significant and positive predictors of strategic independence in the study. The paper discusses research and practical implications, strengths and limitations and areas for future research.

  12. A quasi-independence model to estimate failure rates

    International Nuclear Information System (INIS)

    Colombo, A.G.

    1988-01-01

    The use of a quasi-independence model to estimate failure rates is investigated. Gate valves of nuclear plants are considered, and two qualitative covariates are taken into account: plant location and reactor system. Independence between the two covariates and an exponential failure model are assumed. The failure rate of the components of a given system and plant is assumed to be a constant, but it may vary from one system to another and from one plant to another. This leads to the analysis of a contingency table. A particular feature of the model is the different operating time of the components in the various cells which can also be equal to zero. The concept of independence of the covariates is then replaced by that of quasi-independence. The latter definition, however, is used in a broader sense than usual. Suitable statistical tests are discussed and a numerical example illustrates the use of the method. (author)

  13. How multiple causes combine: independence constraints on causal inference.

    Science.gov (United States)

    Liljeholm, Mimi

    2015-01-01

    According to the causal power view, two core constraints-that causes occur independently (i.e., no confounding) and influence their effects independently-serve as boundary conditions for causal induction. This study investigated how violations of these constraints modulate uncertainty about the existence and strength of a causal relationship. Participants were presented with pairs of candidate causes that were either confounded or not, and that either interacted or exerted their influences independently. Consistent with the causal power view, uncertainty about the existence and strength of causal relationships was greater when causes were confounded or interacted than when unconfounded and acting independently. An elemental Bayesian causal model captured differences in uncertainty due to confounding but not those due to an interaction. Implications of distinct sources of uncertainty for the selection of contingency information and causal generalization are discussed.

  14. Auditor’s Risk Assessment of Independent Directors in Nigeria

    Directory of Open Access Journals (Sweden)

    Salau Abdulmalik

    2017-01-01

    Full Text Available The objective of this study is to investigate the external auditor’s risk assessment of independent directors in Nigeria. The study utilized data from 94 non-financial listed companies on the Nigerian Stock Exchange for the periods 2008-2013. The study used cross-sectional time-series feasible generalized least square regression, which account for heteroscedasticity and autocorrelation to test the influence independent non-executive director on auditor pricing decision in Nigeria. Our result indicates that the proportion of independent non-executive director has a positive relationship with audit fees, suggesting that this class of directors is priced high by the Nigerian auditors. These findings have both policy and practical implication on corporate governance. For instance, future regulatory reforms could consider collaborative board model instead of the insistence on more independent director presence in the boardroom.

  15. A platform independent communication library for distributed computing

    NARCIS (Netherlands)

    Groen, D.; Rieder, S.; Grosso, P.; de Laat, C.; Portegies Zwart, S.

    2010-01-01

    We present MPWide, a platform independent communication library for performing message passing between supercomputers. Our library couples several local MPI applications through a long distance network using, for example, optical links. The implementation is deliberately kept light-weight, platform

  16. Southeast Fishery-Independent Survey (PC1204, ME70)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Southeast Fishery-Independent Survey (SEFIS) was created by the National Marine Fisheries Service in 2010 and operates out of the NOAA Beaufort Laboratory. The...

  17. Fuzzy 5F Analysis of an Independent Chinese Auto Company

    OpenAIRE

    陳, 法恩; 古殿, 幸雄; チン, ホウオン; コドノ, ユキオ; Faen, Chen; Yukio, Kodono

    2014-01-01

     The Chinese market is indispensable to international automobile companies, who are thus expanding investment in the country’s automotive industry. To increase their market share in China, automobile manufacturers and independent automotive enterprises have implemented a series of management strategies. Consequently, competition in China is becoming increasingly intense. At the same time, Chinese automobile companies have no international brand recognition.  In this paper, an independent auto...

  18. Interactions between contemporary American independent cinema and popular music culture

    OpenAIRE

    Nicholls, Matthew

    2011-01-01

    In recent years, many American independent films have become increasingly engaged with popular music culture and have used various forms of pop music in their soundtracks to various effects. Disparate films from a variety of genres use different forms of popular music in different ways, however these negotiations with pop music and its cultural surroundings have one true implication: that the 'independentness' (or 'indieness') of these movies is informed, anchored and embellished by their rel...

  19. Independent game development – Developers’ reflections in postmortems

    OpenAIRE

    Suorsa, Noora

    2017-01-01

    Independent computer games have gained a lot of popularity in the past few years. Digital distribution methods and networks have made it possible for indie games to find more players, and get an easier access to markets, and get noticed by the consumers, than it was during the traditional brick and mortar shop based retail and console game dominant era. The increased popularity and number of indie games and developers has made indie games an interesting research area. Research of independent ...

  20. Culture independent PCR: an alternative enzyme discovery strategy

    DEFF Research Database (Denmark)

    Jacobsen, Jonas; Lydolph, Magnus; Lange, Lene

    2005-01-01

    Degenerate primers were designed for use in a culture-independent PCR screening of DNA from composite fungal communities, inhabiting residues of corn stovers and leaves. According to similarity searches and alignments amplified clone sequences affiliated with glycosyl hydrolase family 7 and glyco...... the value of culture-independent PCR in microbial diversity studies and could add to development of a new enzyme screening technology....

  1. Newspapers and Parties: How Advertising Revenues Created an Independent Press

    OpenAIRE

    Maria Petrova

    2009-01-01

    Does economic development promote media freedom? Do higher advertising revenues tend to make media outlets independent of political groups?in?uence? Using data on the 19th century American newspapers, I show that in places with higher advertising revenues, newspapers were more likely to be independent from political parties. Similar results hold when local advertising rates are instrumented by regulations on outdoor advertising and newspaper distribution. I also show that newly created newspa...

  2. Biologic consequences of Stat1-independent IFN signaling

    OpenAIRE

    Gil, M. Pilar; Bohn, Erwin; O'Guin, Andrew K.; Ramana, Chilakamarti V.; Levine, Beth; Stark, George R.; Virgin, Herbert W.; Schreiber, Robert D.

    2001-01-01

    Although Stat1 is required for many IFN-dependent responses, recent work has shown that IFNγ functions independently of Stat1 to affect the growth of tumor cells or immortalized fibroblasts. We now demonstrate that both IFNγ and IFNα/β regulate proliferative responses in cells of the mononuclear phagocyte lineage derived from Stat1-null mice. Using both representational difference analysis and gene arrays, we show that IFNγ exerts its Stat1-independent actions on m...

  3. The non conventional gas, a factor of energy independence?

    International Nuclear Information System (INIS)

    Jacques Percebois

    2011-01-01

    As the recent exploitation of non conventional gases (or shale gases) has dramatically changed the energy deal in the USA, and therefore the energy world market, these gases seem to be a factor of energy independence for countries which possess such resources, but also create environmental constrains. The author describes how shale gas produces a technological revolution, and discusses how it can be a factor for the diversification of the energy mix, and above all a way to reconquer some energy independence

  4. Independent directors’ board networks and controlling shareholders’ tunneling behavior

    OpenAIRE

    Chen, Yunsen; Wang, Yutao; Lin, Le

    2014-01-01

    As one of the channels by which board directors build important relationships, board networks can affect the governance role of independent directors. Defining director board networks as their connections based on direct ties they establish when serving on at least one common board, this paper explores the role of the network centrality of independent directors in restraining tunneling behavior by controlling shareholders in the Chinese capital market. Our empirical evidence shows that tunnel...

  5. Online Crowdfunding Campaign for an Independent Video Game

    OpenAIRE

    Kivikangas, Inessa

    2014-01-01

    Over the past several years online reward-model crowdfunding platforms have become a popular tool for raising funds among independent game developers. Big success of several brilliant indie titles brought to the online crowdfunding platforms Kickstarter and Indiegogo hundreds of hopeful independent developers. However, apart from creating an excellent game indie developers have to be able to reach out to their audience and capture attention of potential supporters and gaming media. Time and e...

  6. Device-independent entanglement certification of all entangled states

    OpenAIRE

    Bowles, Joseph; Šupić, Ivan; Cavalcanti, Daniel; Acín, Antonio

    2018-01-01

    We present a method to certify the entanglement of all bipartite entangled quantum states in a device-independent way. This is achieved by placing the state in a quantum network and constructing a correlation inequality based on an entanglement witness for the state. Our method is device-independent, in the sense that entanglement can be certified from the observed statistics alone, under minimal assumptions on the underlying physics. Conceptually, our results borrow ideas from the field of s...

  7. Independence: proposing an initial framework for occupational therapy.

    Science.gov (United States)

    Collins, Bethan

    2017-11-01

    The concept of independence is common in occupational therapy theory and practice but has rarely been clearly defined or conceptualized within in occupational therapy literature and there seems to be no standard definition. This can result in ambiguity, which potentially jeopardizes client-centred practice. This paper proposes an occupational therapy independence framework (OTIF) that synthesizes the range of characterizations of independence in a practically useful and occupation-centred manner. A review of literature, clinical experience, doctoral research and conversations with occupational therapists and disabled people, in particular those involved in a disability activism group and people with physical disabilities, has led to the development of the OTIF. Independence and interdependence, as characterized in the OTIF, occur when an individual exerts choice over occupational performance and can engage in occupations in a manner acceptable to the individual. Interdependence results when occupations are performed with another person whereas independence involves solitary occupational performance. Dependence typically results from inability to choose occupations or a mismatch between performance capacity and environmental factors. The OTIF has the potential to clarify the conceptualization of independence within occupational therapy theory and practice. This initial proposal is presented to stimulate debate and discussion.

  8. Volume independence in large Nc QCD-like gauge theories

    International Nuclear Information System (INIS)

    Kovtun, Pavel; Uensal, Mithat; Yaffe, Laurence G.

    2007-01-01

    Volume independence in large N c gauge theories may be viewed as a generalized orbifold equivalence. The reduction to zero volume (or Eguchi-Kawai reduction) is a special case of this equivalence. So is temperature independence in confining phases. A natural generalization concerns volume independence in 'theory space' of quiver gauge theories. In pure Yang-Mills theory, the failure of volume independence for sufficiently small volumes (at weak coupling) due to spontaneous breaking of center symmetry, together with its validity above a critical size, nicely illustrate the symmetry realization conditions which are both necessary and sufficient for large N c orbifold equivalence. The existence of a minimal size below which volume independence fails also applies to Yang-Mills theory with antisymmetric representation fermions [QCD(AS)]. However, in Yang-Mills theory with adjoint representation fermions [QCD(Adj)], endowed with periodic boundary conditions, volume independence remains valid down to arbitrarily small size. In sufficiently large volumes, QCD(Adj) and QCD(AS) have a large N c ''orientifold'' equivalence, provided charge conjugation symmetry is unbroken in the latter theory. Therefore, via a combined orbifold-orientifold mapping, a well-defined large N c equivalence exists between QCD(AS) in large, or infinite, volume and QCD(Adj) in arbitrarily small volume. Since asymptotically free gauge theories, such as QCD(Adj), are much easier to study (analytically or numerically) in small volume, this equivalence should allow greater understanding of large N c QCD in infinite volume

  9. Independent checks of linear accelerators equipped with multileaf collimators

    International Nuclear Information System (INIS)

    Pavlikova, I.; Ekendahl, D.; Horakova, I.

    2005-01-01

    National Radiation Protection Institute (NRPI) provides independent checks of therapeutic equipment as a part of state supervision. In the end of 2003, the audit was broaden for linear accelerators equipped with multileaf collimators (MLC). NRPI provides TLD postal audits and on-site independent checks. This contribution describes tests for multileaf collimators and intensity modulated radiation therapy (IMRT) technique that are accomplished within the independent on-site check of linear accelerators. The character and type of tests that are necessary to pursue for multileaf collimator depends on application technique. There are three basic application of the MLC. The first we call 'static MLC' and it serves for replacing conventional blocking or for adjusting the field shape to match the beam's-eye view projection of a planning target volume during an arc rotation of the x-ray beam. This procedure is called conformal radiotherapy. The most advanced technique with MLC is intensity modulated radiation therapy. The dose can be delivered to the patient with IMRT in various different ways: dynamic MLC, segmented MLC and IMRT arc therapy. Independent audits represent an important instrument of quality assurance. Methodology for independent check of static MLC was successfully verified on two types of accelerators: Varian and Elekta. Results from pilot measurements with dynamic MLC imply that the methodology is applicable for Varian accelerators. In the future, the experience with other types of linear accelerators will contribute to renovation, modification, and broaden independent checks methodology. (authors)

  10. Regional Autonomy and Local Democracy: Independent Candidates Cases

    Directory of Open Access Journals (Sweden)

    Suryanto

    2016-11-01

    Full Text Available One of the efforts to achieve local democracy is through the participation of independent candidates in the Direct General Election in the region. The presence of independent candidates in the Direct General Election gives a great hope to change the political structure of the shackles of the old forces. This paper aims to discuss the implication of regional heads coming from independent candidates on the effectiveness of local governance and the implementation of substantive democracy in the region. The method used is a qualitative approach using descriptive research method. The data collection is done through literature approach. Processing data uses Milles and Huberman interactive models, which includes data reduction, data presentation, and conclusion. The study concluded three things: First, the presence of independent candidates in the Direct General Election gives the opportunities to achieve local democracy that is getting bigger, Second, Regional Heads elected from independent candidates face the challenges of the ineffectiveness of regional government, and Third, within certain limits, the power of elected regional heads from independent lane leads to the realization of democracy that is not substantial.

  11. Productive Entry of Foot-and-Mouth Disease Virus via Macropinocytosis Independent of Phosphatidylinositol 3-Kinase

    Science.gov (United States)

    Han, Shi-Chong; Guo, Hui-Chen; Sun, Shi-Qi; Jin, Ye; Wei, Yan-Quan; Feng, Xia; Yao, Xue-Ping; Cao, Sui-Zhong; Xiang Liu, Ding; Liu, Xiang-Tao

    2016-01-01

    Virus entry is an attractive target for therapeutic intervention. Here, using a combination of electron microscopy, immunofluorescence assay, siRNA interference, specific pharmacological inhibitors, and dominant negative mutation, we demonstrated that the entry of foot-and-mouth disease virus (FMDV) triggered a substantial amount of plasma membrane ruffling. We also found that the internalization of FMDV induced a robust increase in fluid-phase uptake, and virions internalized within macropinosomes colocalized with phase uptake marker dextran. During this stage, the Rac1-Pak1 signaling pathway was activated. After specific inhibition on actin, Na+/H+ exchanger, receptor tyrosine kinase, Rac1, Pak1, myosin II, and protein kinase C, the entry and infection of FMDV significantly decreased. However, inhibition of phosphatidylinositol 3-kinase (PI3K) did not reduce FMDV internalization but increased the viral entry and infection to a certain extent, implying that FMDV entry did not require PI3K activity. Results showed that internalization of FMDV exhibited the main hallmarks of macropinocytosis. Moreover, intracellular trafficking of FMDV involves EEA1/Rab5-positive vesicles. The present study demonstrated macropinocytosis as another endocytic pathway apart from the clathrin-mediated pathway. The findings greatly expand our understanding of the molecular mechanisms of FMDV entry into cells, as well as provide potential insights into the entry mechanisms of other picornaviruses. PMID:26757826

  12. Securing financial independence in the legal basis of a central bank

    NARCIS (Netherlands)

    F. Amtenbrink (Fabian)

    2005-01-01

    textabstractTogether with institutional, functional and organizational independence, financial independence constitutes one of the cornerstones of central bank independence, the economic ratio of which has been demonstrated extensively in the literature. In broad terms financial independence may be

  13. Appraising the value of independent EIA follow-up verifiers

    Energy Technology Data Exchange (ETDEWEB)

    Wessels, Jan-Albert, E-mail: janalbert.wessels@nwu.ac.za [School of Geo and Spatial Sciences, Department of Geography and Environmental Management, North-West University, C/O Hoffman and Borcherd Street, Potchefstroom, 2520 (South Africa); Retief, Francois, E-mail: francois.retief@nwu.ac.za [School of Geo and Spatial Sciences, Department of Geography and Environmental Management, North-West University, C/O Hoffman and Borcherd Street, Potchefstroom, 2520 (South Africa); Morrison-Saunders, Angus, E-mail: A.Morrison-Saunders@murdoch.edu.au [School of Geo and Spatial Sciences, Department of Geography and Environmental Management, North-West University, C/O Hoffman and Borcherd Street, Potchefstroom, 2520 (South Africa); Environmental Assessment, School of Environmental Science, Murdoch University, Australia. (Australia)

    2015-01-15

    Independent Environmental Impact Assessment (EIA) follow-up verifiers such as monitoring agencies, checkers, supervisors and control officers are active on various construction sites across the world. There are, however, differing views on the value that these verifiers add and very limited learning in EIA has been drawn from independent verifiers. This paper aims to appraise how and to what extent independent EIA follow-up verifiers add value in major construction projects in the developing country context of South Africa. A framework for appraising the role of independent verifiers was established and four South African case studies were examined through a mixture of site visits, project document analysis, and interviews. Appraisal results were documented in the performance areas of: planning, doing, checking, acting, public participating and integration with other programs. The results indicate that independent verifiers add most value to major construction projects when involved with screening EIA requirements of new projects, allocation of financial and human resources, checking legal compliance, influencing implementation, reporting conformance results, community and stakeholder engagement, integration with self-responsibility programs such as environmental management systems (EMS), and controlling records. It was apparent that verifiers could be more creatively utilized in pre-construction preparation, providing feedback of knowledge into assessment of new projects, giving input to the planning and design phase of projects, and performance evaluation. The study confirms the benefits of proponent and regulator follow-up, specifically in having independent verifiers that disclose information, facilitate discussion among stakeholders, are adaptable and proactive, aid in the integration of EIA with other programs, and instill trust in EIA enforcement by conformance evaluation. Overall, the study provides insight on how to harness the learning opportunities

  14. Appraising the value of independent EIA follow-up verifiers

    International Nuclear Information System (INIS)

    Wessels, Jan-Albert; Retief, Francois; Morrison-Saunders, Angus

    2015-01-01

    Independent Environmental Impact Assessment (EIA) follow-up verifiers such as monitoring agencies, checkers, supervisors and control officers are active on various construction sites across the world. There are, however, differing views on the value that these verifiers add and very limited learning in EIA has been drawn from independent verifiers. This paper aims to appraise how and to what extent independent EIA follow-up verifiers add value in major construction projects in the developing country context of South Africa. A framework for appraising the role of independent verifiers was established and four South African case studies were examined through a mixture of site visits, project document analysis, and interviews. Appraisal results were documented in the performance areas of: planning, doing, checking, acting, public participating and integration with other programs. The results indicate that independent verifiers add most value to major construction projects when involved with screening EIA requirements of new projects, allocation of financial and human resources, checking legal compliance, influencing implementation, reporting conformance results, community and stakeholder engagement, integration with self-responsibility programs such as environmental management systems (EMS), and controlling records. It was apparent that verifiers could be more creatively utilized in pre-construction preparation, providing feedback of knowledge into assessment of new projects, giving input to the planning and design phase of projects, and performance evaluation. The study confirms the benefits of proponent and regulator follow-up, specifically in having independent verifiers that disclose information, facilitate discussion among stakeholders, are adaptable and proactive, aid in the integration of EIA with other programs, and instill trust in EIA enforcement by conformance evaluation. Overall, the study provides insight on how to harness the learning opportunities

  15. How Many Separable Sources? Model Selection In Independent Components Analysis

    Science.gov (United States)

    Woods, Roger P.; Hansen, Lars Kai; Strother, Stephen

    2015-01-01

    Unlike mixtures consisting solely of non-Gaussian sources, mixtures including two or more Gaussian components cannot be separated using standard independent components analysis methods that are based on higher order statistics and independent observations. The mixed Independent Components Analysis/Principal Components Analysis (mixed ICA/PCA) model described here accommodates one or more Gaussian components in the independent components analysis model and uses principal components analysis to characterize contributions from this inseparable Gaussian subspace. Information theory can then be used to select from among potential model categories with differing numbers of Gaussian components. Based on simulation studies, the assumptions and approximations underlying the Akaike Information Criterion do not hold in this setting, even with a very large number of observations. Cross-validation is a suitable, though computationally intensive alternative for model selection. Application of the algorithm is illustrated using Fisher's iris data set and Howells' craniometric data set. Mixed ICA/PCA is of potential interest in any field of scientific investigation where the authenticity of blindly separated non-Gaussian sources might otherwise be questionable. Failure of the Akaike Information Criterion in model selection also has relevance in traditional independent components analysis where all sources are assumed non-Gaussian. PMID:25811988

  16. Enhanced dynamic wedge and independent monitor unit verification

    International Nuclear Information System (INIS)

    Howlett, SJ.

    2005-01-01

    Some serious radiation accidents have occurred around the world during the delivery of radiotherapy treatment. The regrettable incident in Panama clearly indicated the need for independent monitor unit (MU) verification. Indeed the International Atomic Energy Agency (IAEA), after investigating the incident, made specific recommendations for radiotherapy centres which included an independent monitor unit check for all treatments. Independent monitor unit verification is practiced in many radiotherapy centres in developed countries around the world. It is mandatory in USA but not yet in Australia. This paper describes development of an independent MU program, concentrating on the implementation of the Enhanced Dynamic Wedge (EDW) component. The difficult case of non centre of field (COF) calculation points under the EDW was studied in some detail. Results of a survey of Australasian centres regarding the use of independent MU check systems is also presented. The system was developed with reference to MU calculations made by Pinnacle 3 D Radiotherapy Treatment Planning (RTP) system (ADAC - Philips) for 4MV, 6MV and 18MV X-ray beams used at the Newcastle Mater Misericordiae Hospital (NMMH) in the clinical environment. A small systematic error was detected in the equation used for the EDW calculations. Results indicate that COF equations may be used in the non COF situation with similar accuracy to that achieved with profile corrected methods. Further collaborative work with other centres is planned to extend these findings

  17. Remuneration Committee, Board Independence and Top Executive Compensation

    Directory of Open Access Journals (Sweden)

    Chii-Shyan Kuo

    2014-04-01

    Full Text Available In this study, we examine whether the levels and structures of top executive compensation vary discernibly with different levels of board independence. We also examine how the newly mandated adoption of the remuneration committee (RC in Taiwan affects the board independence-executive pay relation. The mandatory establishment of RC for Taiwanese public firms, starting in 2011, is intended to strengthen the reasonableness and effectiveness of the executive compensation structure; thus, it is timely and of interest for practitioners and regulators to understand whether the establishment of RCs can effectively discipline top executive compensation policies. We first find that CEOs of firms that do not appoint independent directors have greater levels of annual pay than is the case for firms that have appointed independent directors, after controlling for the effect of CEO pay determinants. Second, we find that CEO pay for early RC adopters is more closely related to firm performance. Third, we find that the establishing of RCs may decrease CEO pay and enhance the pay-performance association, in particular for firms that have not appointed independent directors; however, this effect is not found to be statistically significant.

  18. Delay-independent stability of genetic regulatory networks.

    Science.gov (United States)

    Wu, Fang-Xiang

    2011-11-01

    Genetic regulatory networks can be described by nonlinear differential equations with time delays. In this paper, we study both locally and globally delay-independent stability of genetic regulatory networks, taking messenger ribonucleic acid alternative splicing into consideration. Based on nonnegative matrix theory, we first develop necessary and sufficient conditions for locally delay-independent stability of genetic regulatory networks with multiple time delays. Compared to the previous results, these conditions are easy to verify. Then we develop sufficient conditions for global delay-independent stability for genetic regulatory networks. Compared to the previous results, this sufficient condition is less conservative. To illustrate theorems developed in this paper, we analyze delay-independent stability of two genetic regulatory networks: a real-life repressilatory network with three genes and three proteins, and a synthetic gene regulatory network with five genes and seven proteins. The simulation results show that the theorems developed in this paper can effectively determine the delay-independent stability of genetic regulatory networks.

  19. Mutual information, perceptual independence, and holistic face perception.

    Science.gov (United States)

    Fitousi, Daniel

    2013-07-01

    The concept of perceptual independence is ubiquitous in psychology. It addresses the question of whether two (or more) dimensions are perceived independently. Several authors have proposed perceptual independence (or its lack thereof) as a viable measure of holistic face perception (Loftus, Oberg, & Dillon, Psychological Review 111:835-863, 2004; Wenger & Ingvalson, Learning, Memory, and Cognition 28:872-892, 2002). According to this notion, the processing of facial features occurs in an interactive manner. Here, I examine this idea from the perspective of two theories of perceptual independence: the multivariate uncertainty analysis (MUA; Garner & Morton, Definitions, models, and experimental paradigms. Psychological Bulletin 72:233-259, 1969), and the general recognition theory (GRT; Ashby & Townsend, Psychological Review 93:154-179, 1986). The goals of the study were to (1) introduce the MUA, (2) examine various possible relations between MUA and GRT using numerical simulations, and (3) apply the MUA to two consensual markers of holistic face perception(-)recognition of facial features (Farah, Wilson, Drain, & Tanaka, Psychological Review 105:482-498, 1998) and the composite face effect (Young, Hellawell, & Hay, Perception 16:747-759, 1987). The results suggest that facial holism is generated by violations of several types of perceptual independence. They highlight the important theoretical role played by converging operations in the study of holistic face perception.

  20. Calibrating EASY-Care independence scale to improve accuracy

    Science.gov (United States)

    Jotheeswaran, A. T.; Dias, Amit; Philp, Ian; Patel, Vikram; Prince, Martin

    2016-01-01

    Background there is currently limited support for the reliability and validity of the EASY-Care independence scale, with little work carried out in low- or middle-income countries. Therefore, we assessed the internal construct validity and hierarchical and classical scaling properties among frail dependent older people in the community. Objective we assessed the internal construct validity and hierarchical and classical scaling properties among frail dependent older people in the community. Methods three primary care physicians administered EASY-Care comprehensive geriatric assessment for 150 frail and/or dependent older people in the primary care setting. A Mokken model was applied to investigate hierarchical scaling properties of EASY-Care independence scale, and internal consistency (Cronbach's alpha) of the scale was also examined. Results we found that EASY-Care independence scale is highly internally consistent and is a strong hierarchical scale, hence providing strong evidence for unidimensionality. However, two items in the scale (unable to use telephone and manage finances) had much lower item Loevinger H coefficients than others. Exclusion of these two items improved the overall internal consistency of the scale. Conclusions the strong performance of the EASY-Care independence scale among community-dwelling frail older people is encouraging. This study confirms that EASY-Care independence scale is highly internally consistent and a strong hierarchical scale. PMID:27496925

  1. Joint Integration Office Independent Review Committee annual report, 1985

    International Nuclear Information System (INIS)

    1986-08-01

    Comprised of seven persons with extensive experience in the issues of nuclear waste, the Independent Review Committee (IRC) provides independent and objective review of Defense Transuranic Waste Program (DTWP) activities managed by the Joint Integration Office (JIO), formerly the Defense Transuranic Waste Lead Organization (TLO). The Committee is ensured a broad, interdisciplinary perspective since its membership includes representatives from the fields of nuclear engineering, nuclear waste transportation, industrial quality control, systems and environmental engineering and state and local government. The scope of IRC activities includes overall review of specific TLO plans, projects and activities, and technical review of particular research and development projects. The Committee makes specific suggestions and recommendations based upon expertise in the field of TRU Waste Management. The IRC operates as a consulting group, under an independent charter providing objective review of program activities. This report summarizes the 12 major topics reviewed by the committee during 1985

  2. Independent community care gerontological nursing: becoming an entrepreneur.

    Science.gov (United States)

    Caffrey, Rosalie A

    2005-08-01

    Few nurses have the experience of developing an independent practice. This ethnographic study explores the process and challenges of becoming an entrepreneur as described by nurses developing independent practices in community care gerontologic nursing. The process included developing a legal contract, marketing strategies, and reimbursement amounts and strategies. Major barriers to implementing this role identified by the nurses included ignorance and confusion by others about their role, financial issues related to an uncertain income, time management, and legal concerns especially around delegation. These were experienced and dedicated nurses who were also risk-takers and enjoyed the independence of practicing nursing because they believed it was meant to be practiced. Suggestions for research, education, and practice are included.

  3. Independent rate and temporal coding in hippocampal pyramidal cells.

    Science.gov (United States)

    Huxter, John; Burgess, Neil; O'Keefe, John

    2003-10-23

    In the brain, hippocampal pyramidal cells use temporal as well as rate coding to signal spatial aspects of the animal's environment or behaviour. The temporal code takes the form of a phase relationship to the concurrent cycle of the hippocampal electroencephalogram theta rhythm. These two codes could each represent a different variable. However, this requires the rate and phase to vary independently, in contrast to recent suggestions that they are tightly coupled, both reflecting the amplitude of the cell's input. Here we show that the time of firing and firing rate are dissociable, and can represent two independent variables: respectively the animal's location within the place field, and its speed of movement through the field. Independent encoding of location together with actions and stimuli occurring there may help to explain the dual roles of the hippocampus in spatial and episodic memory, or may indicate a more general role of the hippocampus in relational/declarative memory.

  4. Model-independent effects of Δ excitation in nucleon polarizabilities

    International Nuclear Information System (INIS)

    Pascalutsa, Vladimir; Phillips, Daniel R.

    2003-01-01

    Model-independent effects of Δ(1232) excitation on nucleon polarizabilities are computed in a Lorentz-invariant fashion. We find a large effect of relative order (M Δ -M)/M in some of the spin polarizabilities, with the backward spin polarizability receiving the largest contribution. Similar subleading effects are found to be important in the fourth-order spin-independent polarizabilities α Eν , α E2 , β Mν , and β M2 . Combining our results with those for the model-independent effects of pion loops we obtain predictions for spin and fourth-order polarizabilities which compare favorably with the results of a recent dispersion-relation analysis of data

  5. Cap-independent translation of plant viral RNAs.

    Science.gov (United States)

    Kneller, Elizabeth L Pettit; Rakotondrafara, Aurélie M; Miller, W Allen

    2006-07-01

    The RNAs of many plant viruses lack a 5' cap and must be translated by a cap-independent mechanism. Here, we discuss the remarkably diverse cap-independent translation elements that have been identified in members of the Potyviridae, Luteoviridae, and Tombusviridae families, and genus Tobamovirus. Many other plant viruses have uncapped RNAs but their translation control elements are uncharacterized. Cap-independent translation elements of plant viruses differ strikingly from those of animal viruses: they are smaller (translation factors, and speculate on their mechanism of action and their roles in the virus replication cycle. Much remains to be learned about how these elements enable plant viruses to usurp the host translational machinery.

  6. Loss of Financial Management Independence After Brain Injury: Survivors' Experiences.

    Science.gov (United States)

    Koller, Kathryn; Woods, Lindsay; Engel, Lisa; Bottari, Carolina; Dawson, Deirdre R; Nalder, Emily

    2016-01-01

    This pilot study explored the experiences of brain injury survivors after a change in financial management (FM) independence. Using a qualitative descriptive design, 6 participants with acquired brain injury were recruited from a community brain injury organization and participated in semistructured interviews. Data were analyzed using thematic analysis. Three themes emerged from the interviews: (1) trajectory of FM change, involving family members as key change agents; (2) current FM situation, involving FM strategies such as automatic deposits and restricted budgets; and (3) the struggle for control, in which survivors desired control while also accepting supports for FM. This study identifies some of the challenges brain injury survivors face in managing their finances and the adjustment associated with a loss of FM independence. Occupational therapists should be aware of clients' experiences when supporting them through a change in independence. Copyright © 2016 by the American Occupational Therapy Association, Inc.

  7. Is Cognitive Activity of Speech Based On Statistical Independence?

    DEFF Research Database (Denmark)

    Feng, Ling; Hansen, Lars Kai

    2008-01-01

    This paper explores the generality of COgnitive Component Analysis (COCA), which is defined as the process of unsupervised grouping of data such that the ensuing group structure is well-aligned with that resulting from human cognitive activity. The hypothesis of {COCA} is ecological......: the essentially independent features in a context defined ensemble can be efficiently coded using a sparse independent component representation. Our devised protocol aims at comparing the performance of supervised learning (invoking cognitive activity) and unsupervised learning (statistical regularities) based...... on similar representations, and the only difference lies in the human inferred labels. Inspired by the previous research on COCA, we introduce a new pair of models, which directly employ the independent hypothesis. Statistical regularities are revealed at multiple time scales on phoneme, gender, age...

  8. Independent verification: operational phase liquid metal breeder reactors

    International Nuclear Information System (INIS)

    Bourne, P.B.

    1981-01-01

    The Fast Flux Test Facility (FFTF) recently achieved 100-percent power and now is in the initial stages of operation as a test reactor. An independent verification program has been established to assist in maintaining stable plant conditions, and to assure the safe operation of the reactor. Independent verification begins with the development of administrative procedures to control all other procedures and changes to the plant configurations. The technical content of the controlling procedures is subject to independent verification. The actual accomplishment of test procedures and operational maneuvers is witnessed by personnel not responsible for operating the plant. Off-normal events are analyzed, problem reports from other operating reactors are evaluated, and these results are used to improve on-line performance. Audits are used to confirm compliance with established practices and to identify areas where individual performance can be improved

  9. Multifractal analysis of managed and independent float exchange rates

    Science.gov (United States)

    Stošić, Darko; Stošić, Dusan; Stošić, Tatijana; Stanley, H. Eugene

    2015-06-01

    We investigate multifractal properties of daily price changes in currency rates using the multifractal detrended fluctuation analysis (MF-DFA). We analyze managed and independent floating currency rates in eight countries, and determine the changes in multifractal spectrum when transitioning between the two regimes. We find that after the transition from managed to independent float regime the changes in multifractal spectrum (position of maximum and width) indicate an increase in market efficiency. The observed changes are more pronounced for developed countries that have a well established trading market. After shuffling the series, we find that the multifractality is due to both probability density function and long term correlations for managed float regime, while for independent float regime multifractality is in most cases caused by broad probability density function.

  10. Mass independent isotope effects and their observations in nature

    International Nuclear Information System (INIS)

    Thiemens, M.H.

    2002-01-01

    In 1983, Thiemens and Heidenreich reported the first chemically produced mass independent isotope effect. A significant feature of the fractionation was that it identically produced the isotopic relation observed in the calcium-aluminum inclusions in the Allende meteorite. This δ 17 O=δ 18 O composition had previously been thought to represent a nucleosynthetic component as no chemical process was capable of producing a mass independent isotopic composition. It now appears nearly certain that the meteoritic oxygen isotopic anomalies were produced by chemical, rather than nuclear, processes. Since oxygen is the major element in stony planets this represents a major event in the formation of the solar system. In a recent review (Thiemens, 1999), it has been shown that mass independent isotopic compositions are pervasive in the Earth's atmosphere. Molecules which have been demonstrated to possess mass independent isotopic compositions include: O 2 , O 3 , CO 2 , CO, and N 2 O. In each case, the specific nature of the mass independent isotopic composition has provided details of their atmospheric chemistry that could not have been obtained by any other measurement technique. Most recently, solid materials have been observed to possess mass independent isotopic composition. In this paper, these observations are briefly discussed. These solid reservoirs include: 1) carbonates and sulphates from Mars, 2) terrestrial aerosol sulphate, 3) sulphides and sulphates from the Earth, ranging in time from 3.8 to 2.2 billion years before present, 4) sulphates from the Namibian desert and 5) the Antartic Dry Valleys. The information obtained from these measurements is extraordinarily wide ranging, extending from understanding the history of Martian atmosphereregolith interaction to the evolution of the oxygen in the Earth's earliest atmosphere. As was the case for gas phase species, this information and insight could not have been obtained by any other measurement technique

  11. Cineclube Antonio das Mortes and its independent film production

    Directory of Open Access Journals (Sweden)

    Marina da Costa Campos

    2014-07-01

    Full Text Available This article analysis the production of experimental films made by Cineclube Antonio das Mortes (CAM in 1980, in Goiania, Through the term "independent film". This work is an initial study, therefore, it’s intended, first, to discuss the various conceptions given to “independent cinema” in Brazilian cinema history, from the late 1940s until 1980. Then, this work will try to understand how this production of this Cineclube approaches or moves away from the different conceptions that this term has acquired over the decades.

  12. Independent Technical (open-quotes Red Teamclose quotes) Reviews

    International Nuclear Information System (INIS)

    Thullen, P.; Bennett, D.R.; Kosiewicz, S.T.; Weaver, D.L.

    1995-01-01

    Offices under the Assistant Secretary for Environmental Restoration and Waste Management (EM) in the Department of Energy (DOE) and some National Laboratories are using Independent Technical or open-quotes Red Teamclose quotes Reviews to understand and improve the performance of major projects, major system acquisitions, programs and organizations. A core group formed in 1991 by Los Alamos National Laboratory and Sandia National Laboratories, has organized teams of commercial and private consultants to perform over fifteen Independent Technical Reviews (ITRs) throughout the DOE Complex. This paper discusses: review initiation, team formation, methodology, site response, and observations gathered over the past three years

  13. Work teams help independents make best use of technology

    International Nuclear Information System (INIS)

    Greene, J.F.; Rees, G.D.

    1992-01-01

    This paper reports that application of new technology in multidisciplinary team environments can help independent producers prosper in the world's evolving oil and gas industry. Independents face changes on both a macro and micro level involving resource access, capital pricing, tools, systems, and processes which are progressing at a disconcerting pace. Many opportunities, challenges, successes, and failures will transpire in this environment. Organizations and individuals will succeed or fail based on the ability to adapt, create, capitalize, and excel in a business world that fails to offer a clear vision

  14. Central bank independence and its effect on money market stability

    OpenAIRE

    MSc. Anera Alishani

    2012-01-01

    Since 1990s many countries have moved toward greater central bank independence (CBI) by either amending their Central Bank’s laws or writing them de novo. Also countries of Western Balkans and many other transition countries have moved toward greater CBI. There are many potential benefits associated with greater CBI, and one of them is stable growth of money and liquidity. For a given level of money market development the hypothesis is that a more independent CB is likely to promote more stab...

  15. Independent component analysis of edge information for face recognition

    CERN Document Server

    Karande, Kailash Jagannath

    2013-01-01

    The book presents research work on face recognition using edge information as features for face recognition with ICA algorithms. The independent components are extracted from edge information. These independent components are used with classifiers to match the facial images for recognition purpose. In their study, authors have explored Canny and LOG edge detectors as standard edge detection methods. Oriented Laplacian of Gaussian (OLOG) method is explored to extract the edge information with different orientations of Laplacian pyramid. Multiscale wavelet model for edge detection is also propos

  16. Model-independent cosmological constraints from growth and expansion

    Science.gov (United States)

    L'Huillier, Benjamin; Shafieloo, Arman; Kim, Hyungjin

    2018-05-01

    Reconstructing the expansion history of the Universe from Type Ia supernovae data, we fit the growth rate measurements and put model-independent constraints on some key cosmological parameters, namely, Ωm, γ, and σ8. The constraints are consistent with those from the concordance model within the framework of general relativity, but the current quality of the data is not sufficient to rule out modified gravity models. Adding the condition that dark energy density should be positive at all redshifts, independently of its equation of state, further constrains the parameters and interestingly supports the concordance model.

  17. Central Bank Independence and Inflation IN EU-28

    Directory of Open Access Journals (Sweden)

    Beju Daniela-Georgeta

    2017-12-01

    Full Text Available Today, both policymakers and academicians consider that the central bank’s main goal is to guarantee price stability. The central bank can sustain the government’s economic policies, but only without prejudicing this objective. In order to focus on price stability several studies found that central bank should have a high level of independence. This is why during the recent decades the majority of developed countries, but also several emerging economies have employed institutional reforms that conferred their monetary authorities – the central bank – more independence.

  18. A converse to linear independence criteria, valid almost everywhere

    DEFF Research Database (Denmark)

    Fischler, Stéphane; Hussain, Mumtaz; Kristensen, Simon

    We prove a weighted analogue of the Khintchine-Groshev Theorem, where the distance to the nearest integer is replaced by the absolute value. This is subsequently applied to proving the optimality of several linear independence criteria over the field of rational numbers.......We prove a weighted analogue of the Khintchine-Groshev Theorem, where the distance to the nearest integer is replaced by the absolute value. This is subsequently applied to proving the optimality of several linear independence criteria over the field of rational numbers....

  19. Semi-device-independent random-number expansion without entanglement

    International Nuclear Information System (INIS)

    Li Hongwei; Yin Zhenqiang; Wu Yuchun; Zou Xubo; Wang Shuang; Chen Wei; Guo Guangcan; Han Zhengfu

    2011-01-01

    By testing the classical correlation violation between two systems, true random numbers can be generated and certified without applying classical statistical method. In this work, we propose a true random-number expansion protocol without entanglement, where the randomness can be guaranteed only by the two-dimensional quantum witness violation. Furthermore, we only assume that the dimensionality of the system used in the protocol has a tight bound, and the whole protocol can be regarded as a semi-device-independent black-box scenario. Compared with the device-independent random-number expansion protocol based on entanglement, our protocol is much easier to implement and test.

  20. The frequency-independent control method for distributed generation systems

    DEFF Research Database (Denmark)

    Naderi, Siamak; Pouresmaeil, Edris; Gao, Wenzhong David

    2012-01-01

    In this paper a novel frequency-independent control method suitable for distributed generation (DG) is presented. This strategy is derived based on the . abc/. αβ transformation and . abc/. dq transformation of the ac system variables. The active and reactive currents injected by the DG are contr......In this paper a novel frequency-independent control method suitable for distributed generation (DG) is presented. This strategy is derived based on the . abc/. αβ transformation and . abc/. dq transformation of the ac system variables. The active and reactive currents injected by the DG...