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Sample records for biasing seven-transmembrane receptors

  1. Quantitative phosphoproteomics dissection of seven-transmembrane receptor signaling using full and biased agonists

    DEFF Research Database (Denmark)

    Christensen, Gitte L; Kelstrup, Christian D; Lyngsø, Christina

    2010-01-01

    (q)-dependent and -independent AT(1)R signaling. This study provides substantial novel insight into angiotensin II signal transduction and is the first study dissecting the differences between a full agonist and a biased agonist from a 7TMR on a systems-wide scale. Importantly, it reveals a previously unappreciated diversity......Seven-transmembrane receptors (7TMRs) signal through the well described heterotrimeric G proteins but can also activate G protein-independent signaling pathways of which the impact and complexity are less understood. The angiotensin II type 1 receptor (AT(1)R) is a prototypical 7TMR...... and quantity of Galpha(q) protein-independent signaling and uncovers novel signaling pathways. We foresee that the amount and diversity of G protein-independent signaling may be more pronounced than previously recognized for other 7TMRs as well. Quantitative mass spectrometry is a promising tool for evaluation...

  2. Molecular pharmacology of promiscuous seven transmembrane receptors sensing organic nutrients.

    Science.gov (United States)

    Wellendorph, Petrine; Johansen, Lars Dan; Bräuner-Osborne, Hans

    2009-09-01

    A number of highly promiscuous seven transmembrane (7TM) receptors have been cloned and characterized within the last few years. It is noteworthy that many of these receptors are activated broadly by amino acids, proteolytic degradation products, carbohydrates, or free fatty acids and are expressed in taste tissue, the gastrointestinal tract, endocrine glands, adipose tissue, and/or kidney. These receptors thus hold the potential to act as sensors of food intake, regulating, for example, release of incretin hormones from the gut, insulin/glucagon from the pancreas, and leptin from adipose tissue. The promiscuous tendency in ligand recognition of these receptors is in contrast to the typical specific interaction with one physiological agonist seen for most receptors, which challenges the classic "lock-and-key" concept. We here review the molecular mechanisms of nutrient sensing of the calcium-sensing receptor, the G protein-coupled receptor family C, group 6, subtype A (GPRC6A), and the taste1 receptor T1R1/T1R3, which are sensing L-alpha-amino acids, the carbohydrate-sensing T1R2/T1R3 receptor, the proteolytic degradation product sensor GPR93 (also termed GPR92), and the free fatty acid (FFA) sensing receptors FFA1, FFA2, FFA3, GPR84, and GPR120. The involvement of the individual receptors in sensing of food intake has been validated to different degrees because of limited availability of specific pharmacological tools and/or receptor knockout mice. However, as a group, the receptors represent potential drug targets, to treat, for example, type II diabetes by mimicking food intake by potent agonists or positive allosteric modulators. The ligand-receptor interactions of the promiscuous receptors of organic nutrients thus remain an interesting subject of emerging functional importance.

  3. Molecular pharmacological phenotyping of EBI2. An orphan seven-transmembrane receptor with constitutive activity

    DEFF Research Database (Denmark)

    Rosenkilde, Mette M; Benned-Jensen, Tau; Holst, Peter J

    2006-01-01

    Epstein-Barr virus (EBV)-induced receptor 2 (EBI2) is an orphan seven-transmembrane (7TM) receptor originally identified as the most up-regulated gene (>200-fold) in EBV-infected cells. Here we show that EBI2 signals with constitutive activity through Galpha(i) as determined by a receptor...

  4. Promiscuous Seven Transmembrane Receptors Sensing L-α-amino Acids

    DEFF Research Database (Denmark)

    Smajilovic, Sanela; Wellendorph, Petrine; Bräuner-Osborne, Hans

    2014-01-01

    A number of nutrient sensing seven trans-membrane (7TM) receptors have been identified and characterized over the past few years. While the sensing mechanisms to carbohydrates and free fatty acids are well understood, the molecular basis of amino acid sensing has recently come to the limelight....... The present review describes the current status of promiscuous L-α-amino acid sensors, the calcium sensing receptor (CaSR), the GPRC6A receptor, the T1R1/T1R3 receptor and also their molecular pharmacology, expression pattern and physiological significance....

  5. Molecular pharmacology of promiscuous seven transmembrane receptors sensing organic nutrients

    DEFF Research Database (Denmark)

    Wellendorph, Petrine; Johansen, Lars Dan; Bräuner-Osborne, Hans

    2009-01-01

    drug targets, to treat, for example, type II diabetes by mimicking food intake by potent agonists or positive allosteric modulators. The ligand-receptor interactions of the promiscuous receptors of organic nutrients thus remain an interesting subject of emerging functional importance....... in taste tissue, the gastrointestinal tract, endocrine glands, adipose tissue, and/or kidney. These receptors thus hold the potential to act as sensors of food intake, regulating, for example, release of incretin hormones from the gut, insulin/glucagon from the pancreas, and leptin from adipose tissue....... The promiscuous tendency in ligand recognition of these receptors is in contrast to the typical specific interaction with one physiological agonist seen for most receptors, which challenges the classic "lock-and-key" concept. We here review the molecular mechanisms of nutrient sensing of the calcium...

  6. Structure, function and physiological consequences of virally encoded chemokine seven transmembrane receptors

    DEFF Research Database (Denmark)

    Rosenkilde, M M; Smit, M J; Waldhoer, M

    2008-01-01

    A number of human and animal herpes viruses encode G-protein coupled receptors with seven transmembrane (7TM) segments-most of which are clearly related to human chemokine receptors. It appears, that these receptors are used by the virus for immune evasion, cellular transformation, tissue targeting...... pathogenesis is still poorly understood. Here we focus on the current knowledge of structure, function and trafficking patterns of virally encoded chemokine receptors and further address the putative roles of these receptors in virus survival and host -cell and/or -immune system modulation. Finally, we...

  7. Ligand Modulation of the Epstein-Barr Virus-induced Seven-transmembrane Receptor EBI2

    DEFF Research Database (Denmark)

    Benned-Jensen, Tau; Smethurst, Christopher; Holst, Peter Johannes

    2011-01-01

    The Epstein-Barr virus-induced receptor 2 (EBI2) is a constitutively active seven-transmembrane receptor, which was recently shown to orchestrate the positioning of B cells in the follicle. To date, no ligands, endogenously or synthetic, have been identified that modulate EBI2 activity. Here we...... with similar potency. Overexpression of EBI2 profoundly potentiated antibody-stimulated ex vivo proliferation of murine B cells compared with WT cells, whereas this was equivalently reduced for EBI2-deficient B cells. Inhibition of EBI2 constitutive activity suppressed the proliferation in all cases...

  8. A bioluminescence resonance energy transfer 2 (BRET2) assay for monitoring seven transmembrane receptor and insulin receptor crosstalk

    DEFF Research Database (Denmark)

    Sanni, Samra Joke; Kulahin, Nikolaj; Jorgensen, Rasmus

    2017-01-01

    The angiotensin AT1 receptor is a seven transmembrane (7TM) receptor, which mediates the regulation of blood pressure. Activation of angiotensin AT1 receptor may lead to impaired insulin signaling indicating crosstalk between angiotensin AT1 receptor and insulin receptor signaling pathways....... To elucidate the molecular mechanisms behind this crosstalk, we applied the BRET2 technique to monitor the effect of angiotensin II on the interaction between Rluc8 tagged insulin receptor and GFP2 tagged insulin receptor substrates 1, 4, 5 (IRS1, IRS4, IRS5) and Src homology 2 domain-containing protein (Shc......). We demonstrate that angiotensin II reduces the interaction between insulin receptor and IRS1 and IRS4, respectively, while the interaction with Shc is unaffected, and this effect is dependent on Gαq activation. Activation of other Gαq-coupled 7TM receptors led to a similar reduction in insulin...

  9. Evolutionary and Comparative Genomics to Drive Rational Drug Design, with Particular Focus on Neuropeptide Seven-Transmembrane Receptors.

    Science.gov (United States)

    Furlong, Michael; Seong, Jae Young

    2017-01-01

    Seven transmembrane receptors (7TMRs), also known as G protein-coupled receptors, are popular targets of drug development, particularly 7TMR systems that are activated by peptide ligands. Although many pharmaceutical drugs have been discovered via conventional bulk analysis techniques the increasing availability of structural and evolutionary data are facilitating change to rational, targeted drug design. This article discusses the appeal of neuropeptide-7TMR systems as drug targets and provides an overview of concepts in the evolution of vertebrate genomes and gene families. Subsequently, methods that use evolutionary concepts and comparative analysis techniques to aid in gene discovery, gene function identification, and novel drug design are provided along with case study examples.

  10. Seven transmembrane G protein-coupled receptor repertoire of gastric ghrelin cells

    DEFF Research Database (Denmark)

    Engelstoft, Maja S; Park, Won-Mee; Sakata, Ichiro

    2013-01-01

    The molecular mechanisms regulating secretion of the orexigenic-glucoregulatory hormone ghrelin remain unclear. Based on qPCR analysis of FACS-purified gastric ghrelin cells, highly expressed and enriched 7TM receptors were comprehensively identified and functionally characterized using in vitro......, ex vivo and in vivo methods. Five Gαs-coupled receptors efficiently stimulated ghrelin secretion: as expected the β1-adrenergic, the GIP and the secretin receptors but surprisingly also the composite receptor for the sensory neuropeptide CGRP and the melanocortin 4 receptor. A number of Gαi....../o-coupled receptors inhibited ghrelin secretion including somatostatin receptors SSTR1, SSTR2 and SSTR3 and unexpectedly the highly enriched lactate receptor, GPR81. Three other metabolite receptors known to be both Gαi/o- and Gαq/11-coupled all inhibited ghrelin secretion through a pertussis toxin-sensitive Gαi...

  11. A conserved aromatic lock for the tryptophan rotameric switch in TM-VI of seven-transmembrane receptors

    DEFF Research Database (Denmark)

    Holst, Birgitte; Nygaard, Rie; Hansen, Louise Valentin

    2010-01-01

    simulations in rhodopsin demonstrated that rotation around the chi1 torsion angle of Trp-VI:13 brings its side chain close to the equally highly conserved Phe-V:13 (Phe-5.47) in TM-V. In the ghrelin receptor, engineering of high affinity metal-ion sites between these positions confirmed their close spatial...... degree as observed in the constructs where Trp-VI:13 itself was mutated, but again without affecting agonist potency. In a proposed active receptor conformation generated by molecular simulations, where the extracellular segment of TM-VI is tilted inwards in the main ligand-binding pocket, Trp-VI:13......The conserved tryptophan in position 13 of TM-VI (Trp-VI:13 or Trp-6.48) of the CWXP motif located at the bottom of the main ligand-binding pocket in TM-VI is believed to function as a rotameric microswitch in the activation process of seven-transmembrane (7TM) receptors. Molecular dynamics...

  12. Metal ion site engineering indicates a global toggle switch model for seven-transmembrane receptor activation

    DEFF Research Database (Denmark)

    Elling, Christian E; Frimurer, Thomas M; Gerlach, Lars-Ole

    2006-01-01

    for monoamine binding in TM-III, was used as the starting point to engineer activating metal ion sites between the extracellular segments of the beta2-adrenergic receptor. Cu(II) and Zn(II) alone and in complex with aromatic chelators acted as potent (EC50 decreased to 0.5 microm) and efficacious agonists...

  13. PheVI:09 (Phe6.44) as a sliding microswitch in seven-transmembrane (7TM) G protein-coupled receptor activation

    DEFF Research Database (Denmark)

    Valentin-Hansen, Louise; Holst, Birgitte; Frimurer, Thomas M

    2012-01-01

    In seven-transmembrane (7TM), G protein-coupled receptors, highly conserved residues function as microswitches, which alternate between different conformations and interaction partners in an extended allosteric interface between the transmembrane segments performing the large scale conformational......-V into a tight pocket generated by five hydrophobic residues protruding from TM-III and TM-V. Of these, the residue in position III:16 (3.40) (often an Ile or Val) appears to function as a barrier or gate for the transition between inactive and active conformation. Mutational analysis showed that PheVI:09...... an aromatic microswitch that stabilizes the active, outward tilted conformation of TM-VI relative to TM-III by sliding into a tight hydrophobic pocket between TM-III and TM-V and that the hydrophobic residue in position III:16 constitutes a gate for this transition....

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

    DEFF Research Database (Denmark)

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

    2006-01-01

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

  15. Identification and functional comparison of seven-transmembrane G-protein-coupled BILF1 receptors in recently discovered nonhuman primate lymphocryptoviruses

    DEFF Research Database (Denmark)

    Spiess, Katja; Fares, Suzan; Sparre-Ulrich, Alexander H

    2015-01-01

    Coevolution of herpesviruses with their respective host has resulted in a delicate balance between virus-encoded immune evasion mechanisms and host antiviral immunity. BILF1 encoded by human Epstein-Barr virus (EBV) is a 7-transmembrane (7TM) G-protein-coupled receptor (GPCR) with multiple immuno...

  16. SGIP1 alters internalization and modulates signaling of activated cannabinoid receptor 1 in a biased manner

    Czech Academy of Sciences Publication Activity Database

    Hájková, Alena; Techlovská, Šárka; Dvořáková, Michaela; Chambers, Jayne Nicole; Kumpošt, Jiří; Hubálková, Pavla; Prezeau, L.; Blahoš, Jaroslav

    2016-01-01

    Roč. 107, léto (2016), s. 201-214 ISSN 0028-3908 R&D Projects: GA ČR GAP303/12/2408 Institutional support: RVO:68378050 Keywords : Seven transmembrane receptors * G-protein coupled receptors * Cannabinoid receptor 1 * Protein-protein interactions * Bias signaling * Receptor endocytosis Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.012, year: 2016

  17. Selective elimination of high constitutive activity or chemokine binding in the human herpesvirus 8 encoded seven transmembrane oncogene ORF74

    DEFF Research Database (Denmark)

    Rosenkilde, M M; Kledal, T N; Holst, Peter Johannes

    2000-01-01

    Open reading frame 74 (ORF74) encoded by human herpesvirus 8 is a highly constitutively active seven transmembrane (7TM) receptor stimulated by angiogenic chemokines, e.g. growth-related oncogene-alpha, and inhibited by angiostatic chemokines e.g. interferon-gamma-inducible protein. Transgenic mice...

  18. Agonists and inverse agonists for the herpesvirus 8-encoded constitutively active seven-transmembrane oncogene product, ORF-74

    DEFF Research Database (Denmark)

    Rosenkilde, M M; Kledal, T N; Bräuner-Osborne, Hans

    1999-01-01

    A number of CXC chemokines competed with similar, nanomolar affinity against 125I-interleukin-8 (IL-8) binding to ORF-74, a constitutively active seven-transmembrane receptor encoded by human herpesvirus 8. However, in competition against 125I-labeled growth-related oncogene (GRO)-alpha, the ORF-74...

  19. Corruption of host seven-transmembrane proteins by pathogenic microbes: a common theme in animals and plants?

    Science.gov (United States)

    Panstruga, Ralph; Schulze-Lefert, Paul

    2003-04-01

    Human diseases like AIDS, malaria, and pneumonia are caused by pathogens that corrupt host chemokine G-protein coupled receptors for molecular docking. Comparatively, little is known about plant host factors that are required for pathogenesis and that may serve as receptors for the entry of pathogenic microbes. Here, we review potential analogies between human chemokine receptors and the plant seven-transmembrane MLO protein, a candidate serving a dual role as docking molecule and defence modulator for the phytopathogenic powdery mildew fungus.

  20. Quantitative phosphoproteomics dissection of 7TM receptor signaling using full and biased agonists

    DEFF Research Database (Denmark)

    Christensen, Gitte L; Kelstrup, Christian D; Lyngsø, Christina

    2010-01-01

    only activates the Gaq protein-independent signaling.e quantified more than ten thousand phosphorylation sites of which 1183 were regulated by Angiotensin II or its analogue SII Angiotensin II. 36% of the AT1R regulated phosphorylations were regulated by SII Angiotensin II. Analysis of phosphorylation...... into Angiotensin II signal transduction and is the first study dissecting the differences between a full agonist and a biased agonist from a 7TMR on a systems-wide scale. Importantly, it reveals a previously unappreciated diversity and quantity of Gaq protein-independent signaling and uncovers novel signaling......Seven-transmembrane receptors (7TMRs) signal through the well described heterotrimeric G proteins, but can also activate G protein-independent signaling pathways of which the impact and complexity are less understood. The Angiotensin II type 1 receptor (AT1R) is a prototypical 7TMR and an important...

  1. Differential expression of a novel seven transmembrane domain protein in epididymal fat from aged and diabetic mice.

    Science.gov (United States)

    Yang, H; Egan, J M; Rodgers, B D; Bernier, M; Montrose-Rafizadeh, C

    1999-06-01

    To identify novel seven transmembrane domain proteins from 3T3-L1 adipocytes, we used PCR to amplify 3T3-L1 adipocyte complementary DNA (cDNA) with primers homologous to the N- and C-termini of pancreatic glucagon-like peptide-1 (GLP-1) receptor. We screened a cDNA library prepared from fully differentiated 3T3-L1 adipocytes using a 500-bp cDNA PCR product probe. Herein describes the isolation and characterization of a 1.6-kb cDNA clone that encodes a novel 298-amino acid protein that we termed TPRA40 (transmembrane domain protein of 40 kDa regulated in adipocytes). TPRA40 has seven putative transmembrane domains and shows little homology with the known GLP-1 receptor or with other G protein-coupled receptors. The levels of TPRA40 mRNA and protein were higher in 3T3-L1 adipocytes than in 3T3-L1 fibroblasts. TPRA40 is present in a number of mouse and human tissues. Interestingly, TPRA40 mRNA levels were significantly increased by 2- to 3-fold in epididymal fat of 24-month-old mice vs. young controls as well as in db/db and ob/ob mice vs. nondiabetic control littermates. No difference in TPRA40 mRNA levels was observed in brain, heart, skeletal muscle, liver, or kidney. Furthermore, no difference in TPRA40 expression was detected in brown fat of ob/ob mice when compared with age-matched controls. Taken together, these data suggest that TPRA40 represents a novel membrane-associated protein whose expression in white adipose tissue is altered with aging and type 2 diabetes.

  2. Probing Biased Signaling in Chemokine Receptors

    DEFF Research Database (Denmark)

    Amarandi, Roxana Maria; Hjortø, Gertrud Malene; Rosenkilde, Mette Marie

    2016-01-01

    The chemokine system mediates leukocyte migration during homeostatic and inflammatory processes. Traditionally, it is described as redundant and promiscuous, with a single chemokine ligand binding to different receptors and a single receptor having several ligands. Signaling of chemokine receptors...... of others has been termed signaling bias and can accordingly be grouped into ligand bias, receptor bias, and tissue bias. Bias has so far been broadly overlooked in the process of drug development. The low number of currently approved drugs targeting the chemokine system, as well as the broad range...... of failed clinical trials, reflects the need for a better understanding of the chemokine system. Thus, understanding the character, direction, and consequence of biased signaling in the chemokine system may aid the development of new therapeutics. This review describes experiments to assess G protein...

  3. Biased and g protein-independent signaling of chemokine receptors

    DEFF Research Database (Denmark)

    Steen, Anne; Larsen, Olav; Thiele, Stefanie

    2014-01-01

    ), different receptors (with the same ligand), or different tissues or cells (for the same ligand-receptor pair). Most often biased signaling is differentiated into G protein-dependent and β-arrestin-dependent signaling. Yet, it may also cover signaling differences within these groups. Moreover, it may...

  4. Biased agonism of the calcium-sensing receptor

    DEFF Research Database (Denmark)

    Thomsen, Alex Rojas Bie; Hvidtfeldt, Maja; Bräuner-Osborne, Hans

    2012-01-01

    After the discovery of molecules modulating G protein-coupled receptors (GPCRs) that are able to selectively affect one signaling pathway over others for a specific GPCR, thereby "biasing" the signaling, it has become obvious that the original model of GPCRs existing in either an "on" or "off...... through recruitment of ß-arrestins. Next, by measuring activity of all three signaling pathways we found that barium, spermine, neomycin, and tobramycin act as biased agonist in terms of efficacy and/or potency. Finally, polyamines and aminoglycosides in general were biased in their potencies toward ERK1...

  5. Functionally biased signalling properties of 7TM receptors - opportunities for drug development for the ghrelin receptor

    DEFF Research Database (Denmark)

    Sivertsen, B; Holliday, N; Madsen, A N

    2013-01-01

    UNLABELLED: The ghrelin receptor is a 7 transmembrane (7TM) receptor involved in a variety of physiological functions including growth hormone secretion, increased food intake and fat accumulation as well as modulation of reward and cognitive functions. Because of its important role in metabolism...... and energy expenditure, the ghrelin receptor has become an important therapeutic target for drug design and the development of anti-obesity compounds. However, none of the compounds developed so far have been approved for commercial use. Interestingly, the ghrelin receptor is able to signal through several...... review, we have described how ligands and mutations in the 7TM receptor may bias the receptors to favour either one G-protein over another or to promote G-protein independent signalling pathways rather than G-protein-dependent pathways. For the ghrelin receptor, both agonist and inverse agonists have...

  6. Biased signaling of G protein-coupled receptors - From a chemokine receptor CCR7 perspective

    DEFF Research Database (Denmark)

    Jørgensen, Astrid Sissel; Rosenkilde, Mette M; Hjortø, Gertrud M

    2018-01-01

    of CCL21 displays an extraordinarily strong glycosaminoglycan (GAG) binding, CCR7 plays a central role in coordinating the meeting between mature antigen presenting DCs and naïve T-cells which normally takes place in the lymph nodes (LNs). This process is a prerequisite for the initiation of an antigen...... the cell-based immune system is controlled. Bias comes in three forms; ligand-, receptor- and tissue-bias. Biased signaling is increasingly being recognized as playing an important role in contributing to the fine-tuned coordination of immune cell chemotaxis. In the current review we discuss the recent...

  7. Uniform isotope labeling of a eukaryotic seven-transmembrane helical protein in yeast enables high-resolution solid-state NMR studies in the lipid environment

    International Nuclear Information System (INIS)

    Fan Ying; Shi Lichi; Ladizhansky, Vladimir; Brown, Leonid S.

    2011-01-01

    Overexpression of isotope-labeled multi-spanning eukaryotic membrane proteins for structural NMR studies is often challenging. On the one hand, difficulties with achieving proper folding, membrane insertion, and native-like post-translational modifications frequently disqualify bacterial expression systems. On the other hand, eukaryotic cell cultures can be prohibitively expensive. One of the viable alternatives, successfully used for producing proteins for solution NMR studies, is yeast expression systems, particularly Pichia pastoris. We report on successful implementation and optimization of isotope labeling protocols, previously used for soluble secreted proteins, to produce homogeneous samples of a eukaryotic seven-transmembrane helical protein, rhodopsin from Leptosphaeria maculans. Even in shake-flask cultures, yields exceeded 5 mg of purified uniformly 13 C, 15 N-labeled protein per liter of culture. The protein was stable (at least several weeks at 5°C) and functionally active upon reconstitution into lipid membranes at high protein-to-lipid ratio required for solid-state NMR. The samples gave high-resolution 13 C and 15 N solid-state magic angle spinning NMR spectra, amenable to a detailed structural analysis. We believe that similar protocols can be adopted for challenging mammalian targets, which often resist characterization by other structural methods.

  8. Unique interaction pattern for a functionally biased ghrelin receptor agonist

    DEFF Research Database (Denmark)

    Sivertsen, Bjørn Behrens; Lang, Manja; Frimurer, Thomas M.

    2011-01-01

    Based on the conformationally constrained D-Trp-Phe-D-Trp (wFw) core of the prototype inverse agonist [D-Arg(1),D-Phe(5),D-Trp(7,9),Leu(11)]substance P, a series of novel, small, peptide-mimetic agonists for the ghrelin receptor were generated. By using various simple, ring-constrained spacers...... connecting the D-Trp-Phe-D-Trp motif with the important C-terminal carboxyamide group, 40 nm agonism potency was obtained and also in one case (wFw-Isn-NH(2), where Isn is isonipecotic acid) ~80% efficacy. However, in contrast to all previously reported ghrelin receptor agonists, the piperidine-constrained w......Fw-Isn-NH(2) was found to be a functionally biased agonist. Thus, wFw-Isn-NH(2) mediated potent and efficacious signaling through the Ga(q) and ERK1/2 signaling pathways, but in contrast to all previous ghrelin receptor agonists it did not signal through the serum response element, conceivably the Ga(12...

  9. High constitutive activity of a virus-encoded seven transmembrane receptor in the absence of the conserved DRY motif (Asp-Arg-Tyr) in transmembrane helix 3

    DEFF Research Database (Denmark)

    Rosenkilde, Mette M; Kledal, Thomas N; Schwartz, Thue W

    2005-01-01

    -driven transcriptional activity through a pertussis toxin-sensitive manner. Gs and Gq were not activated constitutively as determined by the lack of inositol phosphate turnover and activities of the three transcription factors: cAMP response element-binding protein (CREB), nuclear factor-kappaB, and nuclear factor...

  10. The Extracellular Surface of the GLP-1 Receptor Is a Molecular Trigger for Biased Agonism.

    Science.gov (United States)

    Wootten, Denise; Reynolds, Christopher A; Smith, Kevin J; Mobarec, Juan C; Koole, Cassandra; Savage, Emilia E; Pabreja, Kavita; Simms, John; Sridhar, Rohan; Furness, Sebastian G B; Liu, Mengjie; Thompson, Philip E; Miller, Laurence J; Christopoulos, Arthur; Sexton, Patrick M

    2016-06-16

    Ligand-directed signal bias offers opportunities for sculpting molecular events, with the promise of better, safer therapeutics. Critical to the exploitation of signal bias is an understanding of the molecular events coupling ligand binding to intracellular signaling. Activation of class B G protein-coupled receptors is driven by interaction of the peptide N terminus with the receptor core. To understand how this drives signaling, we have used advanced analytical methods that enable separation of effects on pathway-specific signaling from those that modify agonist affinity and mapped the functional consequence of receptor modification onto three-dimensional models of a receptor-ligand complex. This yields molecular insights into the initiation of receptor activation and the mechanistic basis for biased agonism. Our data reveal that peptide agonists can engage different elements of the receptor extracellular face to achieve effector coupling and biased signaling providing a foundation for rational design of biased agonists. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  11. Biased Agonism of Endogenous Opioid Peptides at the μ-Opioid Receptor.

    Science.gov (United States)

    Thompson, Georgina L; Lane, J Robert; Coudrat, Thomas; Sexton, Patrick M; Christopoulos, Arthur; Canals, Meritxell

    2015-08-01

    Biased agonism is having a major impact on modern drug discovery, and describes the ability of distinct G protein-coupled receptor (GPCR) ligands to activate different cell signaling pathways, and to result in different physiologic outcomes. To date, most studies of biased agonism have focused on synthetic molecules targeting various GPCRs; however, many of these receptors have multiple endogenous ligands, suggesting that "natural" bias may be an unappreciated feature of these GPCRs. The μ-opioid receptor (MOP) is activated by numerous endogenous opioid peptides, remains an attractive therapeutic target for the treatment of pain, and exhibits biased agonism in response to synthetic opiates. The aim of this study was to rigorously assess the potential for biased agonism in the actions of endogenous opioids at the MOP in a common cellular background, and compare these to the effects of the agonist d-Ala2-N-MePhe4-Gly-ol enkephalin (DAMGO). We investigated activation of G proteins, inhibition of cAMP production, extracellular signal-regulated kinase 1 and 2 phosphorylation, β-arrestin 1/2 recruitment, and MOP trafficking, and applied a novel analytical method to quantify biased agonism. Although many endogenous opioids displayed signaling profiles similar to that of DAMGO, α-neoendorphin, Met-enkephalin-Arg-Phe, and the putatively endogenous peptide endomorphin-1 displayed particularly distinct bias profiles. These may represent examples of natural bias if it can be shown that they have different signaling properties and physiologic effects in vivo compared with other endogenous opioids. Understanding how endogenous opioids control physiologic processes through biased agonism can reveal vital information required to enable the design of biased opioids with improved pharmacological profiles and treat diseases involving dysfunction of the endogenous opioid system. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

  12. Heart Failure Therapeutics on the Basis of a Biased Ligand of the Angiotensin-2 Type 1 Receptor Rationale and Design of the BLAST-AHF Study (Biased Ligand of the Angiotensin Receptor Study in Acute Heart Failure)

    NARCIS (Netherlands)

    Felker, G. Michael; Butler, Javed; Collins, Sean P.; Cotter, Gad; Davison, Beth A.; Ezekowitz, Justin A.; Filippatos, Gerasimos; Levy, Phillip D.; Metra, Marco; Ponikowski, Piotr; Soergel, David G.; Teerlink, John R.; Violin, Jonathan D.; Voors, Adriaan A.; Pang, Peter S.

    The BLAST-AHF (Biased Ligand of the Angiotensin Receptor Study in Acute Heart Failure) study is designed to test the efficacy and safety of TRV027, a novel biased ligand of the angiotensin-2 type 1 receptor, in patients with acute heart failure (AHF). AHF remains a major public health problem, and

  13. A method for the quantification of biased signalling at constitutively active receptors.

    Science.gov (United States)

    Hall, David A; Giraldo, Jesús

    2018-06-01

    Biased agonism, the ability of an agonist to differentially activate one of several signal transduction pathways when acting at a given receptor, is an increasingly recognized phenomenon at many receptors. The Black and Leff operational model lacks a way to describe constitutive receptor activity and hence inverse agonism. Thus, it is impossible to analyse the biased signalling of inverse agonists using this model. In this theoretical work, we develop and illustrate methods for the analysis of biased inverse agonism. Methods were derived for quantifying biased signalling in systems that demonstrate constitutive activity using the modified operational model proposed by Slack and Hall. The methods were illustrated using Monte Carlo simulations. The Monte Carlo simulations demonstrated that, with an appropriate experimental design, the model parameters are 'identifiable'. The method is consistent with methods based on the measurement of intrinsic relative activity (RA i ) (ΔΔlogR or ΔΔlog(τ/K a )) proposed by Ehlert and Kenakin and their co-workers but has some advantages. In particular, it allows the quantification of ligand bias independently of 'system bias' removing the requirement to normalize to a standard ligand. In systems with constitutive activity, the Slack and Hall model provides methods for quantifying the absolute bias of agonists and inverse agonists. This provides an alternative to methods based on RA i and is complementary to the ΔΔlog(τ/K a ) method of Kenakin et al. in systems where use of that method is inappropriate due to the presence of constitutive activity. © 2018 The British Pharmacological Society.

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

    Science.gov (United States)

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

    2018-01-01

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

  15. Molecular identification of the first SIFamide receptor

    DEFF Research Database (Denmark)

    Jørgensen, Lars M; Hauser, Frank; Cazzamali, Giuseppe

    2006-01-01

    , an impressive sequence conservation (67-77% amino acid sequence identities between the seven-transmembrane areas; 82-87% sequence similarities). The identification of well-conserved SIFamide receptor orthologues in all other insects with a sequenced genome, suggests that the SIFamide/receptor couple must have...... an essential function in arthropods. This paper is the first report on the identification of a SIFamide receptor....

  16. G Protein and β-arrestin signaling bias at the ghrelin receptor.

    Science.gov (United States)

    Evron, Tama; Peterson, Sean M; Urs, Nikhil M; Bai, Yushi; Rochelle, Lauren K; Caron, Marc G; Barak, Larry S

    2014-11-28

    The G protein-coupled ghrelin receptor GHSR1a is a potential pharmacological target for treating obesity and addiction because of the critical role ghrelin plays in energy homeostasis and dopamine-dependent reward. GHSR1a enhances growth hormone release, appetite, and dopamine signaling through G(q/11), G(i/o), and G(12/13) as well as β-arrestin-based scaffolds. However, the contribution of individual G protein and β-arrestin pathways to the diverse physiological responses mediated by ghrelin remains unknown. To characterize whether a signaling bias occurs for GHSR1a, we investigated ghrelin signaling in a number of cell-based assays, including Ca(2+) mobilization, serum response factor response element, stress fiber formation, ERK1/2 phosphorylation, and β-arrestin translocation, utilizing intracellular second loop and C-tail mutants of GHSR1a. We observed that GHSR1a and β-arrestin rapidly form metastable plasma membrane complexes following exposure to an agonist, but replacement of the GHSR1a C-tail by the tail of the vasopressin 2 receptor greatly stabilizes them, producing complexes observable on the plasma membrane and also in endocytic vesicles. Mutations of the contiguous conserved amino acids Pro-148 and Leu-149 in the GHSR1a intracellular second loop generate receptors with a strong bias to G protein and β-arrestin, respectively, supporting a role for conformation-dependent signaling bias in the wild-type receptor. Our results demonstrate more balance in GHSR1a-mediated ERK signaling from G proteins and β-arrestin but uncover an important role for β-arrestin in RhoA activation and stress fiber formation. These findings suggest an avenue for modulating drug abuse-associated changes in synaptic plasticity via GHSR1a and indicate the development of GHSR1a-biased ligands as a promising strategy for selectively targeting downstream signaling events. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  17. Endomorphin-2: a biased agonist at the μ-opioid receptor.

    Science.gov (United States)

    Rivero, Guadalupe; Llorente, Javier; McPherson, Jamie; Cooke, Alex; Mundell, Stuart J; McArdle, Craig A; Rosethorne, Elizabeth M; Charlton, Steven J; Krasel, Cornelius; Bailey, Christopher P; Henderson, Graeme; Kelly, Eamonn

    2012-08-01

    Previously we correlated the efficacy for G protein activation with that for arrestin recruitment for a number of agonists at the μ-opioid receptor (MOPr) stably expressed in HEK293 cells. We suggested that the endomorphins (endomorphin-1 and -2) might be biased toward arrestin recruitment. In the present study, we investigated this phenomenon in more detail for endomorphin-2, using endogenous MOPr in rat brain as well as MOPr stably expressed in HEK293 cells. For MOPr in neurons in brainstem locus ceruleus slices, the peptide agonists [d-Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin (DAMGO) and endomorphin-2 activated inwardly rectifying K(+) current in a concentration-dependent manner. Analysis of these responses with the operational model of pharmacological agonism confirmed that endomorphin-2 had a much lower operational efficacy for G protein-mediated responses than did DAMGO at native MOPr in mature neurons. However, endomorphin-2 induced faster desensitization of the K(+) current than did DAMGO. In addition, in HEK293 cells stably expressing MOPr, the ability of endomorphin-2 to induce phosphorylation of Ser375 in the COOH terminus of the receptor, to induce association of arrestin with the receptor, and to induce cell surface loss of receptors was much more efficient than would be predicted from its efficacy for G protein-mediated signaling. Together, these results indicate that endomorphin-2 is an arrestin-biased agonist at MOPr and the reason for this is likely to be the ability of endomorphin-2 to induce greater phosphorylation of MOPr than would be expected from its ability to activate MOPr and to induce activation of G proteins.

  18. Selectivity of Odorant Receptors in Insects

    Science.gov (United States)

    2012-07-13

    Luetje, C. W., and Robertson, H. M. (2007). A honey bee odorant receptor for the queen substance 9-oxo-2-decenoic acid. Proc. Natl. Acad. Sci. U.S.A...since they might be exposed to a greater number of pharmacolog- ically active compounds than other conventional ligand-gated ion channels and G- protein ...2008). Drosophila odorant receptors are novel seven transmembrane domain proteins that can signal independently of heterotrimeric G proteins

  19. Sex bias in copy number variation of olfactory receptor gene family depends on ethnicity

    Directory of Open Access Journals (Sweden)

    Farideh eShadravan

    2013-03-01

    Full Text Available Gender plays a pivotal role in the human genetic identity and is also manifested in many genetic disorders particularly mental retardation. In this study its effect on copy number variation (CNV, known to cause genetic disorders was explored. As the olfactory receptor (OR repertoire comprises the largest human gene family, it was selected for this study, which was carried out within and between three populations, derived from 150 individuals from the 1000 Genome Project. Analysis of 3872 CNVs detected among 791 OR loci, in which 307 loci showed CNV, revealed the following novel findings: Sex bias in CNV was significantly more prevalent in uncommon than common CNV variants of OR pseudogenes, in which the male genome showed more CNVs; and in one-copy number loss compared to complete deletion of OR pseudogenes; both findings implying a more recent evolutionary role for gender. Sex bias in copy number gain was also detected. Another novel finding was that the observed six bias was largely dependent on ethnicity and was in general absent in East Asians. Using a CNV public database for sick children (ISCA the application of these findings for improving clinical molecular diagnostics is discussed by showing an example of sex bias in CNV among kids with autism. Additional clinical relevance is discussed, as the most polymorphic CNV-enriched OR cluster in the human genome, located on chr 15q11.2, is found near the PWS/AS bi-directionally imprinted region associated with two well-known mental retardation syndromes. As olfaction represents the primitive cognition in most mammals, arguably in competition with the development of a larger brain, the extensive retention of OR pseudogenes in females of this study, might point to a parent-of-origin indirect regulatory role for OR pseudogenes in the embryonic development of human brain. Thus any perturbation in the temporal regulation of olfactory system could lead to developmental delay disorders including

  20. Inter-domain tagging implicates caveolin-1 in insulin receptor trafficking and Erk signaling bias in pancreatic beta-cells

    Directory of Open Access Journals (Sweden)

    Tobias Boothe

    2016-05-01

    Full Text Available Objective: The role and mechanisms of insulin receptor internalization remain incompletely understood. Previous trafficking studies of insulin receptors involved fluorescent protein tagging at their termini, manipulations that may be expected to result in dysfunctional receptors. Our objective was to determine the trafficking route and molecular mechanisms of functional tagged insulin receptors and endogenous insulin receptors in pancreatic beta-cells. Methods: We generated functional insulin receptors tagged with pH-resistant fluorescent proteins between domains. Confocal, TIRF and STED imaging revealed a trafficking pattern of inter-domain tagged insulin receptors and endogenous insulin receptors detected with antibodies. Results: Surprisingly, interdomain-tagged and endogenous insulin receptors in beta-cells bypassed classical Rab5a- or Rab7-mediated endocytic routes. Instead, we found that removal of insulin receptors from the plasma membrane involved tyrosine-phosphorylated caveolin-1, prior to trafficking within flotillin-1-positive structures to lysosomes. Multiple methods of inhibiting caveolin-1 significantly reduced Erk activation in vitro or in vivo, while leaving Akt signaling mostly intact. Conclusions: We conclude that phosphorylated caveolin-1 plays a role in insulin receptor internalization towards lysosomes through flotillin-1-positive structures and that caveolin-1 helps bias physiological beta-cell insulin signaling towards Erk activation. Author Video: Author Video Watch what authors say about their articles Keywords: Insulin receptor internalization, Insulin resistance, Pancreatic islet beta-cells, Autocrine insulin signaling

  1. Known regulators of nitric oxide synthase and arginase are agonists at the human G-protein-coupled receptor GPRC6A

    DEFF Research Database (Denmark)

    Christiansen, Bolette; Wellendorph, Petrine; Bräuner-Osborne, Hans

    2006-01-01

    receptor construct, h6A/5.24, containing the ligand-binding amino-terminal domain of the human GPRC6A and the seven-transmembrane domain and carboxy terminus of the homologous goldfish receptor 5.24. Based on knowledge that this chimera prefers basic L-alpha-amino acids such as arginine, lysine...

  2. Structure of the human glucagon class B G-protein-coupled receptor

    NARCIS (Netherlands)

    Siu, F.Y.; He, M.; de Graaf, C.; Yang, D; Zhang, Z.; Zhou, C.; Han, G.W.; Xu, Q.; Wacker, D.; Joseph, J.S.; Wei, Liu; Lau, J.F.; Cherezov, V.; Katritch, V; Wang, M.W.; Stevens, R.C.

    2013-01-01

    Binding of the glucagon peptide to the glucagon receptor (GCGR) triggers the release of glucose from the liver during fasting; thus GCGR plays an important role in glucose homeostasis. Here we report the crystal structure of the seven transmembrane helical domain of human GCGR at 3.4 Å resolution,

  3. Strontium is a biased agonist of the calcium-sensing receptor in rat medullary thyroid carcinoma 6-23 cells

    DEFF Research Database (Denmark)

    Thomsen, Alex Rojas Bie; Worm, Jesper; Jacobsen, Stine Engesgaard

    2012-01-01

    The calcium-sensing receptor (CaSR)-specific allosteric modulator cinacalcet has revolutionized the treatment of secondary hyperparathyroidism in patients with chronic kidney disease. However, its application is limited to patients with end-stage renal disease because of hypocalcemic side effects......SR-stimulated signaling bias, which may be used to develop novel drugs for the treatment of secondary hyperparathyroidism....

  4. Quantification of mutation-derived bias for alternate mating functionalities of the Saccharomyces cerevisiae Ste2p pheromone receptor.

    Science.gov (United States)

    Choudhary, Pooja; Loewen, Michele C

    2016-01-01

    Although well documented for mammalian G-protein-coupled receptors, alternate functionalities and associated alternate signalling remain to be unequivocally established for the Saccharomyces cerevisiae pheromone Ste2p receptor. Here, evidence supporting alternate functionalities for Ste2p is re-evaluated, extended and quantified. In particular, strong mating and constitutive signalling mutations, focusing on residues S254, P258 and S259 in TM6 of Ste2p, are stacked and investigated in terms of their effects on classical G-protein-mediated signal transduction associated with cell cycle arrest, and alternatively, their impact on downstream mating projection and zygote formation events. In relative dose response experiments, accounting for systemic and observational bias, mutational-derived functional differences were observed, validating the S254L-derived bias for downstream mating responses and highlighting complex relationships between TM6-mutation derived constitutive signalling and ligand-induced functionalities. Mechanistically, localization studies suggest that alterations to receptor trafficking may contribute to mutational bias, in addition to expected receptor conformational stabilization effects. Overall, these results extend previous observations and quantify the contributions of Ste2p variants to mediating cell cycle arrest versus downstream mating functionalities. © Crown copyright 2015.

  5. Conformational Profiling of the AT1 Angiotensin II Receptor Reflects Biased Agonism, G Protein Coupling, and Cellular Context.

    Science.gov (United States)

    Devost, Dominic; Sleno, Rory; Pétrin, Darlaine; Zhang, Alice; Shinjo, Yuji; Okde, Rakan; Aoki, Junken; Inoue, Asuka; Hébert, Terence E

    2017-03-31

    Here, we report the design and use of G protein-coupled receptor-based biosensors to monitor ligand-mediated conformational changes in receptors in intact cells. These biosensors use bioluminescence resonance energy transfer with Renilla luciferase (RlucII) as an energy donor, placed at the distal end of the receptor C-tail, and the small fluorescent molecule FlAsH as an energy acceptor, its binding site inserted at different positions throughout the intracellular loops and C-terminal tail of the angiotensin II type I receptor. We verified that the modifications did not compromise receptor localization or function before proceeding further. Our biosensors were able to capture effects of both canonical and biased ligands, even to the extent of discriminating between different biased ligands. Using a combination of G protein inhibitors and HEK 293 cell lines that were CRISPR/Cas9-engineered to delete Gα q , Gα 11 , Gα 12 , and Gα 13 or β-arrestins, we showed that Gα q and Gα 11 are required for functional responses in conformational sensors in ICL3 but not ICL2. Loss of β-arrestin did not alter biased ligand effects on ICL2P2. We also demonstrate that such biosensors are portable between different cell types and yield context-dependent readouts of G protein-coupled receptor conformation. Our study provides mechanistic insights into signaling events that depend on either G proteins or β-arrestin. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  6. High throughput mutagenesis for identification of residues regulating human prostacyclin (hIP receptor expression and function.

    Directory of Open Access Journals (Sweden)

    Anke Bill

    Full Text Available The human prostacyclin receptor (hIP receptor is a seven-transmembrane G protein-coupled receptor (GPCR that plays a critical role in vascular smooth muscle relaxation and platelet aggregation. hIP receptor dysfunction has been implicated in numerous cardiovascular abnormalities, including myocardial infarction, hypertension, thrombosis and atherosclerosis. Genomic sequencing has discovered several genetic variations in the PTGIR gene coding for hIP receptor, however, its structure-function relationship has not been sufficiently explored. Here we set out to investigate the applicability of high throughput random mutagenesis to study the structure-function relationship of hIP receptor. While chemical mutagenesis was not suitable to generate a mutagenesis library with sufficient coverage, our data demonstrate error-prone PCR (epPCR mediated mutagenesis as a valuable method for the unbiased screening of residues regulating hIP receptor function and expression. Here we describe the generation and functional characterization of an epPCR derived mutagenesis library compromising >4000 mutants of the hIP receptor. We introduce next generation sequencing as a useful tool to validate the quality of mutagenesis libraries by providing information about the coverage, mutation rate and mutational bias. We identified 18 mutants of the hIP receptor that were expressed at the cell surface, but demonstrated impaired receptor function. A total of 38 non-synonymous mutations were identified within the coding region of the hIP receptor, mapping to 36 distinct residues, including several mutations previously reported to affect the signaling of the hIP receptor. Thus, our data demonstrates epPCR mediated random mutagenesis as a valuable and practical method to study the structure-function relationship of GPCRs.

  7. High throughput mutagenesis for identification of residues regulating human prostacyclin (hIP) receptor expression and function.

    Science.gov (United States)

    Bill, Anke; Rosethorne, Elizabeth M; Kent, Toby C; Fawcett, Lindsay; Burchell, Lynn; van Diepen, Michiel T; Marelli, Anthony; Batalov, Sergey; Miraglia, Loren; Orth, Anthony P; Renaud, Nicole A; Charlton, Steven J; Gosling, Martin; Gaither, L Alex; Groot-Kormelink, Paul J

    2014-01-01

    The human prostacyclin receptor (hIP receptor) is a seven-transmembrane G protein-coupled receptor (GPCR) that plays a critical role in vascular smooth muscle relaxation and platelet aggregation. hIP receptor dysfunction has been implicated in numerous cardiovascular abnormalities, including myocardial infarction, hypertension, thrombosis and atherosclerosis. Genomic sequencing has discovered several genetic variations in the PTGIR gene coding for hIP receptor, however, its structure-function relationship has not been sufficiently explored. Here we set out to investigate the applicability of high throughput random mutagenesis to study the structure-function relationship of hIP receptor. While chemical mutagenesis was not suitable to generate a mutagenesis library with sufficient coverage, our data demonstrate error-prone PCR (epPCR) mediated mutagenesis as a valuable method for the unbiased screening of residues regulating hIP receptor function and expression. Here we describe the generation and functional characterization of an epPCR derived mutagenesis library compromising >4000 mutants of the hIP receptor. We introduce next generation sequencing as a useful tool to validate the quality of mutagenesis libraries by providing information about the coverage, mutation rate and mutational bias. We identified 18 mutants of the hIP receptor that were expressed at the cell surface, but demonstrated impaired receptor function. A total of 38 non-synonymous mutations were identified within the coding region of the hIP receptor, mapping to 36 distinct residues, including several mutations previously reported to affect the signaling of the hIP receptor. Thus, our data demonstrates epPCR mediated random mutagenesis as a valuable and practical method to study the structure-function relationship of GPCRs.

  8. Insight into pattern of codon biasness and nucleotide base usage in serotonin receptor gene family from different mammalian species.

    Science.gov (United States)

    Dass, J Febin Prabhu; Sudandiradoss, C

    2012-07-15

    5-HT (5-Hydroxy-tryptamine) or serotonin receptors are found both in central and peripheral nervous system as well as in non-neuronal tissues. In the animal and human nervous system, serotonin produces various functional effects through a variety of membrane bound receptors. In this study, we focus on 5-HT receptor family from different mammals and examined the factors that account for codon and nucleotide usage variation. A total of 110 homologous coding sequences from 11 different mammalian species were analyzed using relative synonymous codon usage (RSCU), correspondence analysis (COA) and hierarchical cluster analysis together with nucleotide base usage frequency of chemically similar amino acid codons. The mean effective number of codon (ENc) value of 37.06 for 5-HT(6) shows very high codon bias within the family and may be due to high selective translational efficiency. The COA and Spearman's rank correlation reveals that the nucleotide compositional mutation bias as the major factors influencing the codon usage in serotonin receptor genes. The hierarchical cluster analysis suggests that gene function is another dominant factor that affects the codon usage bias, while species is a minor factor. Nucleotide base usage was reported using Goldman, Engelman, Stietz (GES) scale reveals the presence of high uracil (>45%) content at functionally important hydrophobic regions. Our in silico approach will certainly help for further investigations on critical inference on evolution, structure, function and gene expression aspects of 5-HT receptors family which are potential antipsychotic drug targets. Copyright © 2012 Elsevier B.V. All rights reserved.

  9. The adhesion G protein-coupled receptor G2 (ADGRG2/GPR64) constitutively activates SRE and NFκB and is involved in cell adhesion and migration

    DEFF Research Database (Denmark)

    Cornelia Peeters, Miriam; Fokkelman, Michiel; Boogaard, Bob

    2015-01-01

    Adhesion G protein-coupled receptors (ADGRs) are believed to be activated by auto-proteolytic cleavage of their very large extracellular N-terminal domains normally acting as a negative regulator of the intrinsically constitutively active seven transmembrane domain. ADGRG2 (or GPR64) which...

  10. Odorant Receptor Modulation: Ternary Paradigm for Mode of Action of Insect Repellents

    Science.gov (United States)

    2012-01-01

    Ostrinia nubilalis. PLoS ONE 5, e8685. Wanner, K.W., Nichols, A.S.,Walden, K.K., Brockmann, A., Luetje, C.W., Robertson, H.M., 2007. A honey bee odorant...allosteric”. Protein Sci. 20, 1119e1124. Christopoulos, A., Kenakin, T., 2002. G protein -coupled receptor allosterism and complexing. Pharmacol. Rev. 54...Newcomb, R.D., Warr, C.G., 2008. Drosophila odorant receptors are novel seven transmembrane domain proteins that can signal independently of

  11. Recent Advances on the Role of G Protein-Coupled Receptors in Hypoxia-Mediated Signaling

    OpenAIRE

    Lappano, Rosamaria; Rigiracciolo, Damiano; De Marco, Paola; Avino, Silvia; Cappello, Anna Rita; Rosano, Camillo; Maggiolini, Marcello; De Francesco, Ernestina Marianna

    2016-01-01

    G protein-coupled receptors (GPCRs) are cell surface proteins mainly involved in signal transmission; however, they play a role also in several pathophysiological conditions. Chemically heterogeneous molecules like peptides, hormones, lipids, and neurotransmitters activate second messengers and induce several biological responses by binding to these seven transmembrane receptors, which are coupled to heterotrimeric G proteins. Recently, additional molecular mechanisms have been involved in GP...

  12. T cell Receptor Alpha Variable 12-2 bias in the immunodominant response to Yellow fever virus

    OpenAIRE

    Bovay, Amandine; Zoete, Vincent; Dolton, Garry; Bulek, Anna M.; Cole, David K.; Rizkallah, Pierre J.; Fuller, Anna; Beck, Konrad; Michielin, Olivier; Speiser, Daniel E.; Sewell, Andrew K.; Fuertes Marraco, Silvia A.

    2018-01-01

    The repertoire of human αβ T-cell receptors (TCRs) is generated via somatic recombination of germline gene segments. Despite this enormous variation, certain epitopes can be immunodominant, associated with high frequencies of antigen-specific T cells and/or exhibit bias toward a TCR gene segment. Here, we studied the TCR repertoire of the HLA-A*0201-restricted epitope LLWNGPMAV (hereafter, A2/LLW) from Yellow Fever virus, which generates an immunodominant CD8 javax.xml.bind.JAXBElement@714aac...

  13. A single extracellular amino acid in Free Fatty Acid Receptor 2 defines antagonist species selectivity and G protein selection bias

    DEFF Research Database (Denmark)

    Sergeev, Eugenia; Hansen, Anders Højgaard; Bolognini, Daniele

    2017-01-01

    selectivity and mutational swap studies confirmed this hypothesis. Extending these studies to agonist function indicated that although the lysine - arginine variation between human and mouse orthologs had limited effect on G protein-mediated signal transduction, removal of positive charge from this residue...... produced a signalling-biased variant of Free Fatty Acid Receptor 2 in which Gi-mediated signalling by both short chain fatty acids and synthetic agonists was maintained whilst there was marked loss of agonist potency for signalling via Gq/11 and G12/13 G proteins. A single residue at the extracellular face...

  14. Biased Type 1 Cannabinoid Receptor Signaling Influences Neuronal Viability in a Cell Culture Model of Huntington Disease.

    Science.gov (United States)

    Laprairie, Robert B; Bagher, Amina M; Kelly, Melanie E M; Denovan-Wright, Eileen M

    2016-03-01

    Huntington disease (HD) is an inherited, autosomal dominant, neurodegenerative disorder with limited treatment options. Prior to motor symptom onset or neuronal cell loss in HD, levels of the type 1 cannabinoid receptor (CB1) decrease in the basal ganglia. Decreasing CB1 levels are strongly correlated with chorea and cognitive deficit. CB1 agonists are functionally selective (biased) for divergent signaling pathways. In this study, six cannabinoids were tested for signaling bias in in vitro models of medium spiny projection neurons expressing wild-type (STHdh(Q7/Q7)) or mutant huntingtin protein (STHdh(Q111/Q111)). Signaling bias was assessed using the Black and Leff operational model. Relative activity [ΔlogR (τ/KA)] and system bias (ΔΔlogR) were calculated relative to the reference compound WIN55,212-2 for Gαi/o, Gαs, Gαq, Gβγ, and β-arrestin1 signaling following treatment with 2-arachidonoylglycerol (2-AG), anandamide (AEA), CP55,940, Δ(9)-tetrahydrocannabinol (THC), cannabidiol (CBD), and THC+CBD (1:1), and compared between wild-type and HD cells. The Emax of Gαi/o-dependent extracellular signal-regulated kinase (ERK) signaling was 50% lower in HD cells compared with wild-type cells. 2-AG and AEA displayed Gαi/o/Gβγ bias and normalized CB1 protein levels and improved cell viability, whereas CP55,940 and THC displayed β-arrestin1 bias and reduced CB1 protein levels and cell viability in HD cells. CBD was not a CB1 agonist but inhibited THC-dependent signaling (THC+CBD). Therefore, enhancing Gαi/o-biased endocannabinoid signaling may be therapeutically beneficial in HD. In contrast, cannabinoids that are β-arrestin-biased--such as THC found at high levels in modern varieties of marijuana--may be detrimental to CB1 signaling, particularly in HD where CB1 levels are already reduced. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  15. Biased Iglambda expression in hypermutated IgD multiple myelomas does not result from receptor revision

    NARCIS (Netherlands)

    van der Burg, M.; Bende, R. J.; Aarts, W. M.; Langerak, A. W.; van Dongen, J. J. M.; van Noesel, C. J. M.

    2002-01-01

    Normal IgM(-)IgD(+) CD38(+) B cells and IgM(-)IgD(+) multiple myelomas (MM) are characterized by Cmu deletion, biased Iglambda expression and hypermutated IgV regions. The predominant Iglambda usage has been proposed as resulting from secondary Ig gene rearrangements during extensive clonal

  16. The emerging role of promiscuous 7TM receptors as chemosensors for food intake

    DEFF Research Database (Denmark)

    Wellendorph, Petrine; Johansen, Lars Dan; Bräuner-Osborne, Hans

    2010-01-01

    review, we describe the molecular mechanisms of nutrient-sensing of the calcium-sensing receptor (CaR), the G protein-coupled receptor family C, group 6, subtype A (GPRC6A), and the taste1 receptor T1R1/T1R3-sensing L-a-amino acids; the carbohydrate-sensing T1R2/T1R3 receptor; the proteolytic degradation......In recent years, several highly promiscuous seven transmembrane (7TM) receptors have been cloned and characterized of which many are activated broadly by amino acids, proteolytic degradation products, carbohydrates, or free fatty acids (FFAs) and are expressed in taste tissue, the gastrointestinal...

  17. The effects of the dopamine D₃ receptor antagonist GSK598809 on attentional bias to palatable food cues in overweight and obese subjects.

    Science.gov (United States)

    Nathan, Pradeep J; O'Neill, Barry V; Mogg, Karin; Bradley, Brendan P; Beaver, John; Bani, Massimo; Merlo-Pich, Emilio; Fletcher, Paul C; Swirski, Bridget; Koch, Annelize; Dodds, Chris M; Bullmore, Edward T

    2012-03-01

    The mesolimbic dopamine system plays a critical role in the reinforcing effects of rewards. Evidence from pre-clinical studies suggests that D₃ receptor antagonists may attenuate the motivational impact of rewarding cues. In this study we examined the acute effects of the D₃ receptor antagonist GSK598809 on attentional bias to rewarding food cues in overweight to obese individuals (n=26, BMI mean=32.7±3.7, range 27-40 kg/m²) who reported binge and emotional eating. We also determined whether individual differences in restrained eating style modulated the effects of GSK598809 on attentional bias. The study utilized a randomized, double-blind, placebo-controlled cross-over design with each participant tested following acute administration of placebo and GSK598809 (175 mg). Attentional bias was assessed by the visual probe task and modified Stroop task using food-related words. Overall GSK598809 had no effects on attentional bias in either the visual probe or food Stroop tasks. However, the effect of GSK598809 on both visual probe and food Stroop attentional bias scores was inversely correlated with a measure of eating restraint allowing the identification of two subpopulations, low- and high-restrained eaters. Low-restrained eaters had a significant attentional bias towards food cues in both tasks under placebo, and this was attenuated by GSK598809. In contrast, high-restrained eaters showed no attentional bias to food cues following either placebo or GSK598809. These findings suggest that excessive attentional bias to food cues generated by individual differences in eating traits can be modulated by D₃ receptor antagonists, warranting further investigation with measures of eating behaviour and weight loss.

  18. BIASED AGONISM OF THREE DIFFERENT CANNABINOID RECEPTOR AGONISTS IN MOUSE BRAIN CORTEX

    Directory of Open Access Journals (Sweden)

    Rebeca Diez-Alarcia

    2016-11-01

    Full Text Available Cannabinoid receptors are able to couple to different families of G-proteins when activated by an agonist drug. It has been suggested that different intracellular responses may be activated depending on the ligand. The goal of the present study was to characterize the pattern of G protein subunit stimulation triggered by three different cannabinoid ligands, THC, WIN55212-2 and ACEA in mouse brain cortex.Stimulation of the [35S]GTPS binding coupled to specific immunoprecipitation with antibodies against different subtypes of G proteins (Gαi1, Gαi2, Gαi3, Gαo, Gαz, Gαs, Gαq/11, and Gα12/13, in the presence of Δ9-THC, WIN55212-2 and ACEA (submaximal concentration 10 µM was determined by Scintillation Proximity Assay (SPA technique in mouse cortex of wild type, CB1 knock-out, CB2 knock-out and CB1/CB2 double knock-out mice. Results show that, in mouse brain cortex, cannabinoid agonists are able to significantly stimulate not only the classical inhibitory Gαi/o subunits but also other G subunits like Gαz, Gαq/11, and Gα12/13. Moreover, the specific pattern of G protein subunit activation is different depending on the ligand. In conclusion, our results demonstrate that, in mice brain native tissue, different exogenous cannabinoid ligands are able to selectively activate different inhibitory and non-inhibitory Gα protein subtypes, through the activation of CB1 and/or CB2 receptors. Results of the present study may help to understand the specific molecular pathways involved in the pharmacological effects of cannabinoid-derived drugs.

  19. Ligand binding to G protein-coupled receptors in tethered cell membranes

    DEFF Research Database (Denmark)

    Martinez, Karen L.; Meyer, Bruno H.; Hovius, Ruud

    2003-01-01

    for the surface immobilization of membrane proteins was developed using the prototypic seven transmembrane neurokinin-1 receptor. The receptor was expressed as a biotinylated protein in mammalian cells. Membranes from cell homogenates were selectively immobilized on glass surfaces covered with streptavidin. TIRF...... measurements showed that a fluorescent agonist binds to the receptor on the sensor surface with similar affinity as to the receptor in live cells. This approach offers the possibility to investigate minute amounts of membrane protein in an active form and in its native environment without purification....

  20. Receptor oligomerization in family B1 of G-protein-coupled receptors

    DEFF Research Database (Denmark)

    Roed, Sarah Norklit; Ørgaard, Anne; Jørgensen, Rasmus

    2012-01-01

    , the glucagon receptor, and the receptors for parathyroid hormone (PTHR1 and PTHR2). The dysregulation of several family B1 receptors is involved in diseases, such as diabetes, chronic inflammation, and osteoporosis which underlines the pathophysiological importance of this GPCR subfamily. In spite of this......, investigation of family B1 receptor oligomerization and especially its pharmacological importance is still at an early stage. Even though GPCR oligomerization is a well-established phenomenon, there is a need for more investigations providing a direct link between these interactions and receptor functionality......The superfamily of the seven transmembrane G-protein-coupled receptors (7TM/GPCRs) is the largest family of membrane-associated receptors. GPCRs are involved in the pathophysiology of numerous human diseases, and they constitute an estimated 30-40% of all drug targets. During the last two decades...

  1. Molecular modeling of ligand-receptor interactions in the OR5 olfactory receptor.

    Science.gov (United States)

    Singer, M S; Shepherd, G M

    1994-06-02

    Olfactory receptors belong to the superfamily of seven transmembrane domain, G protein-coupled receptors. In order to begin analysis of mechanisms of receptor activation, a computer model of the OR5 olfactory receptor has been constructed and compared with other members of this superfamily. We have tested docking of the odor molecule lyral, which is known to activate the OR5 receptor. The results point to specific ligand-binding residues on helices III through VII that form a binding pocket in the receptor. Some of these residues occupy sequence positions identical to ligand-binding residues conserved among other superfamily members. The results provide new insights into possible molecular mechanisms of odor recognition and suggest hypotheses to guide future experimental studies using site-directed mutagenesis.

  2. Identification of biased sectors in emission data using a combination of chemical transport model and receptor model

    Science.gov (United States)

    Uranishi, Katsushige; Ikemori, Fumikazu; Nakatsubo, Ryohei; Shimadera, Hikari; Kondo, Akira; Kikutani, Yuki; Asano, Katsuyoshi; Sugata, Seiji

    2017-10-01

    This study presented a comparison approach with multiple source apportionment methods to identify which sectors of emission data have large biases. The source apportionment methods for the comparison approach included both receptor and chemical transport models, which are widely used to quantify the impacts of emission sources on fine particulate matter of less than 2.5 μm in diameter (PM2.5). We used daily chemical component concentration data in the year 2013, including data for water-soluble ions, elements, and carbonaceous species of PM2.5 at 11 sites in the Kinki-Tokai district in Japan in order to apply the Positive Matrix Factorization (PMF) model for the source apportionment. Seven PMF factors of PM2.5 were identified with the temporal and spatial variation patterns and also retained features of the sites. These factors comprised two types of secondary sulfate, road transportation, heavy oil combustion by ships, biomass burning, secondary nitrate, and soil and industrial dust, accounting for 46%, 17%, 7%, 14%, 13%, and 3% of the PM2.5, respectively. The multiple-site data enabled a comprehensive identification of the PM2.5 sources. For the same period, source contributions were estimated by air quality simulations using the Community Multiscale Air Quality model (CMAQ) with the brute-force method (BFM) for four source categories. Both models provided consistent results for the following three of the four source categories: secondary sulfates, road transportation, and heavy oil combustion sources. For these three target categories, the models' agreement was supported by the small differences and high correlations between the CMAQ/BFM- and PMF-estimated source contributions to the concentrations of PM2.5, SO42-, and EC. In contrast, contributions of the biomass burning sources apportioned by CMAQ/BFM were much lower than and little correlated with those captured by the PMF model, indicating large uncertainties in the biomass burning emissions used in the

  3. Family C 7TM receptor dimerization and activation

    DEFF Research Database (Denmark)

    Bonde, Marie Mi; Sheikh, Søren P; Hansen, Jakob Lerche

    2006-01-01

    The family C seven transmembrane (7TM) receptors constitutes a small and especially well characterized subfamily of the large 7TM receptor superfamily. Approximately 50% of current prescription drugs target 7TM receptors, this biologically important family represents the largest class of drug...... to be fully defined. This review presents the biochemical support for family C 7TM receptor dimerization and discusses its importance for receptor biosynthesis, surface expression, ligand binding and activation, since lessons learnt here may well be applicable to the whole superfamily of 7TM receptors.......-targets today. It is well established that family C 7TM receptors form homo- or hetero-dimers on the cell surface of living cells. The large extra-cellular domains (ECD) have been crystallized as a dimer in the presence and absence of agonist. Upon agonist binding, the dimeric ECD undergoes large conformational...

  4. A G Protein-biased Designer G Protein-coupled Receptor Useful for Studying the Physiological Relevance of Gq/11-dependent Signaling Pathways.

    Science.gov (United States)

    Hu, Jianxin; Stern, Matthew; Gimenez, Luis E; Wanka, Lizzy; Zhu, Lu; Rossi, Mario; Meister, Jaroslawna; Inoue, Asuka; Beck-Sickinger, Annette G; Gurevich, Vsevolod V; Wess, Jürgen

    2016-04-08

    Designerreceptorsexclusivelyactivated by adesignerdrug (DREADDs) are clozapine-N-oxide-sensitive designer G protein-coupled receptors (GPCRs) that have emerged as powerful novel chemogenetic tools to study the physiological relevance of GPCR signaling pathways in specific cell types or tissues. Like endogenous GPCRs, clozapine-N-oxide-activated DREADDs do not only activate heterotrimeric G proteins but can also trigger β-arrestin-dependent (G protein-independent) signaling. To dissect the relative physiological relevance of G protein-mediatedversusβ-arrestin-mediated signaling in different cell types or physiological processes, the availability of G protein- and β-arrestin-biased DREADDs would be highly desirable. In this study, we report the development of a mutationally modified version of a non-biased DREADD derived from the M3muscarinic receptor that can activate Gq/11with high efficacy but lacks the ability to interact with β-arrestins. We also demonstrate that this novel DREADD is activein vivoand that cell type-selective expression of this new designer receptor can provide novel insights into the physiological roles of G protein (Gq/11)-dependentversusβ-arrestin-dependent signaling in hepatocytes. Thus, this novel Gq/11-biased DREADD represents a powerful new tool to study the physiological relevance of Gq/11-dependent signaling in distinct tissues and cell types, in the absence of β-arrestin-mediated cellular effects. Such studies should guide the development of novel classes of functionally biased ligands that show high efficacy in various pathophysiological conditions but display a reduced incidence of side effects. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  5. Plasticity of Signaling by Spinal Estrogen Receptor α, κ-Opioid Receptor, and Metabotropic Glutamate Receptors over the Rat Reproductive Cycle Regulates Spinal Endomorphin 2 Antinociception: Relevance of Endogenous-Biased Agonism.

    Science.gov (United States)

    Liu, Nai-Jiang; Murugaiyan, Vijaya; Storman, Emiliya M; Schnell, Stephen A; Kumar, Arjun; Wessendorf, Martin W; Gintzler, Alan R

    2017-11-15

    We previously showed that intrathecal application of endomorphin 2 [EM2; the highly specific endogenous μ-opioid receptor (MOR) ligand] induces antinociception that varies with stage of the rat estrous cycle: minimal during diestrus and prominent during proestrus. Earlier studies, however, did not identify proestrus-activated signaling strategies that enable spinal EM2 antinociception. We now report that in female rats, increased spinal dynorphin release and κ-opioid receptor (KOR) signaling, as well as the emergence of glutamate-activated metabotropic glutamate receptor 1 (mGluR 1 ) signaling, are critical to the transition from an EM2 nonresponsive state (during diestrus) to an analgesically responsive state (during proestrus). Differential signaling by mGluR 1 , depending on its activation by membrane estrogen receptor α (mERα; during diestrus) versus glutamate (during proestrus), concomitant with the ebb and flow of spinal dynorphin/KOR signaling, functions as a switch, preventing or promoting, respectively, spinal EM2 antinociception. Importantly, EM2 and glutamate-containing varicosities appose spinal neurons that express MOR along with mGluRs and mERα, suggesting that signaling mechanisms regulating analgesic effectiveness of intrathecally applied EM2 also pertain to endogenous EM2. Regulation of spinal EM2 antinociception by both the nature of the endogenous mGluR 1 activator (i.e., endogenous biased agonism at mGluR 1 ) and changes in spinal dynorphin/KOR signaling represent a novel mechanism for modulating analgesic responsiveness to endogenous EM2 (and perhaps other opioids). This points the way for developing noncanonical pharmacological approaches to pain management by harnessing endogenous opioids for pain relief. SIGNIFICANCE STATEMENT The current prescription opioid abuse epidemic underscores the urgency to develop alternative pharmacotherapies for managing pain. We find that the magnitude of spinal endomorphin 2 (EM2) antinociception not only

  6. Role of protease-activated receptor-2 in inflammation, and its possible implications as a putative mediator of periodontitis

    Directory of Open Access Journals (Sweden)

    M Holzhausen

    2005-03-01

    Full Text Available Proteinase-activated receptor-2 (PAR2 belongs to a novel subfamily of G-protein-coupled receptors with seven-transmembrane domains. This receptor is widely distributed throughout the body and seems to be importantly involved in inflammatory processes. PAR2 can be activated by serine proteases such as trypsin, mast cell tryptase, and bacterial proteases, such as gingipain produced by Porphyromonas gingivalis. This review describes the current stage of knowledge of the possible mechanisms that link PAR2 activation with periodontal disease, and proposes future therapeutic strategies to modulate the host response in the treatment of periodontitis.

  7. G protein-coupled receptor 39 deficiency is associated with pancreatic islet dysfunction

    DEFF Research Database (Denmark)

    Holst, Birgitte; Egerod, Kristoffer L; Jin, Chunyu

    2009-01-01

    G protein-coupled receptor (GPR)-39 is a seven-transmembrane receptor expressed mainly in endocrine and metabolic tissues that acts as a Zn(++) sensor signaling mainly through the G(q) and G(12/13) pathways. The expression of GPR39 is regulated by hepatocyte nuclear factor (HNF)-1alpha and HNF-4...... tolerance both during oral and iv glucose tolerance tests, and Gpr39(-/-) mice had decreased plasma insulin response to oral glucose. Islet architecture was normal in the Gpr39 null mice, but expression of Pdx-1 and Hnf-1alpha was reduced. Isolated, perifused islets from Gpr39 null mice secreted less...

  8. A Hydrogen-Bonded Polar Network in the Core of the Glucagon-Like Peptide-1 Receptor Is a Fulcrum for Biased Agonism: Lessons from Class B Crystal Structures

    OpenAIRE

    Wootten, Denise; Reynolds, Christopher A.; Koole, Cassandra; Smith, Kevin J.; Mobarec, Juan C.; Simms, John; Quon, Tezz; Coudrat, Thomas; Furness, Sebastian G. B.; Miller, Laurence J.; Christopoulos, Arthur; Sexton, Patrick M.

    2016-01-01

    The glucagon-like peptide 1 (GLP-1) receptor is a class B G protein-coupled receptor (GPCR) that is a key target for treatments for type II diabetes and obesity. This receptor, like other class B GPCRs, displays biased agonism, though the physiologic significance of this is yet to be elucidated. Previous work has implicated R2.60190, N3.43240, Q7.49394, and H6.52363 as key residues involved in peptide-mediated biased agonism, with R2.60190, N3.43240, and Q7.49394 predicted to form a polar int...

  9. Dopamine receptor blockade attenuates the general incentive motivational effects of noncontingently delivered rewards and reward-paired cues without affecting their ability to bias action selection.

    Science.gov (United States)

    Ostlund, Sean B; Maidment, Nigel T

    2012-01-01

    Environmental cues affect our behavior in a variety of ways. Despite playing an invaluable role in guiding our daily activities, such cues also appear to trigger the harmful, compulsive behaviors that characterize addiction and other disorders of behavioral control. In instrumental conditioning, rewards and reward-paired cues bias action selection and invigorate reward-seeking behaviors, and appear to do so through distinct neurobehavioral processes. Although reward-paired cues are known to invigorate performance through a dopamine-dependent incentive motivational process, it is not known if dopamine also mediates the influence of rewards and reward-paired cues over action selection. The current study contrasted the effects of systemic administration of the nonspecific dopamine receptor antagonist flupentixol on response invigoration and action bias in Pavlovian-instrumental transfer, a test of cue-elicited responding, and in instrumental reinstatement, a test of noncontingent reward-elicited responding. Hungry rats were trained on two different stimulus-outcome relationships (eg, tone-grain pellets and noise-sucrose solution) and two different action-outcome relationships (eg, left press-grain and right press-sucrose). At test, we found that flupentixol pretreatment blocked the response invigoration generated by the cues but spared their ability to bias action selection to favor the action whose outcome was signaled by the cue being presented. The response-biasing influence of noncontingent reward deliveries was also unaffected by flupentixol. Interestingly, although flupentixol had a modest effect on the immediate response invigoration produced by those rewards, it was particularly potent in countering the lingering enhancement of responding produced by multiple reward deliveries. These findings indicate that dopamine mediates the general incentive motivational effects of noncontingent rewards and reward-paired cues but does not support their ability to bias

  10. Adrenergic Agonists Bind to Adrenergic-Receptor-Like Regions of the Mu Opioid Receptor, Enhancing Morphine and Methionine-Enkephalin Binding: A New Approach to "Biased Opioids"?

    Science.gov (United States)

    Root-Bernstein, Robert; Turke, Miah; Subhramanyam, Udaya K Tiruttani; Churchill, Beth; Labahn, Joerg

    2018-01-17

    Extensive evidence demonstrates functional interactions between the adrenergic and opioid systems in a diversity of tissues and organs. While some effects are due to receptor and second messenger cross-talk, recent research has revealed an extracellular, allosteric opioid binding site on adrenergic receptors that enhances adrenergic activity and its duration. The present research addresses whether opioid receptors may have an equivalent extracellular, allosteric adrenergic binding site that has similar enhancing effects on opioid binding. Comparison of adrenergic and opioid receptor sequences revealed that these receptors share very significant regions of similarity, particularly in some of the extracellular and transmembrane regions associated with adrenergic binding in the adrenergic receptors. Five of these shared regions from the mu opioid receptor (muOPR) were synthesized as peptides and tested for binding to adrenergic, opioid and control compounds using ultraviolet spectroscopy. Adrenergic compounds bound to several of these muOPR peptides with low micromolar affinity while acetylcholine, histamine and various adrenergic antagonists did not. Similar studies were then conducted with purified, intact muOPR with similar results. Combinations of epinephrine with methionine enkephalin or morphine increased the binding of both by about half a log unit. These results suggest that muOPR may be allosterically enhanced by adrenergic agonists.

  11. Modulation of constitutive activity and signaling bias of the ghrelin receptor by conformational constraint in the second extracellular loop

    DEFF Research Database (Denmark)

    Mokrosinski, Jacek; Frimurer, Thomas M; Sivertsen, Bjoern

    2012-01-01

    Based on a rare, natural Glu for Ala204(C+6) variant located six residues after the conserved Cys residue in extracellular loop 2 (ECL2b) associated with selective elimination of the high constitutive signaling of the ghrelin receptor, this loop was subjected to a detailed structure functional....... Moreover, the constitutive activity of the receptor was inhibited by Zn(2+) binding in an engineered metal-ion site stabilizing an a-helical conformation of this loop segment. It is concluded that the high constitutive activity of the ghrelin receptor is dependent upon flexibility in the C-terminal segment...

  12. Conversion of agonist site to metal-ion chelator site in the beta(2)-adrenergic receptor

    DEFF Research Database (Denmark)

    Elling, C E; Thirstrup, K; Holst, Birgitte

    1999-01-01

    Previously metal-ion sites have been used as structural and functional probes in seven transmembrane receptors (7TM), but as yet all the engineered sites have been inactivating. Based on presumed agonist interaction points in transmembrane III (TM-III) and -VII of the beta(2)-adrenergic receptor,...... as generic, pharmacologic tools to switch 7TM receptors with engineered metal-ion sites on or off at will.......Previously metal-ion sites have been used as structural and functional probes in seven transmembrane receptors (7TM), but as yet all the engineered sites have been inactivating. Based on presumed agonist interaction points in transmembrane III (TM-III) and -VII of the beta(2)-adrenergic receptor......, in this paper we construct an activating metal-ion site between the amine-binding Asp-113 in TM-III-or a His residue introduced at this position-and a Cys residue substituted for Asn-312 in TM-VII. No increase in constitutive activity was observed in the mutant receptors. Signal transduction was activated...

  13. Identification of serine 348 on the apelin receptor as a novel regulatory phosphorylation site in apelin-13-induced G protein-independent biased signaling.

    Science.gov (United States)

    Chen, Xiaoyu; Bai, Bo; Tian, Yanjun; Du, Hui; Chen, Jing

    2014-11-07

    Phosphorylation plays vital roles in the regulation of G protein-coupled receptor (GPCR) functions. The apelin and apelin receptor (APJ) system is involved in the regulation of cardiovascular function and central control of body homeostasis. Here, using tandem mass spectrometry, we first identified phosphorylated serine residues in the C terminus of APJ. To determine the role of phosphorylation sites in APJ-mediated G protein-dependent and -independent signaling and function, we induced a mutation in the C-terminal serine residues and examined their effects on the interaction between APJ with G protein or GRK/β-arrestin and their downstream signaling. Mutation of serine 348 led to an elimination of both GRK and β-arrestin recruitment to APJ induced by apelin-13. Moreover, APJ internalization and G protein-independent ERK signaling were also abolished by point mutation at serine 348. In contrast, this mutant at serine residues had no demonstrable impact on apelin-13-induced G protein activation and its intracellular signaling. These findings suggest that mutation of serine 348 resulted in inactive GRK/β-arrestin. However, there was no change in the active G protein thus, APJ conformation was biased. These results provide important information on the molecular interplay and impact of the APJ function, which may be extrapolated to design novel drugs for cardiac hypertrophy based on this biased signal pathway. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  14. Functional Consequences of Glucagon-like Peptide-1 Receptor Cross-talk and Trafficking

    DEFF Research Database (Denmark)

    Roed, Sarah Noerklit; Nøhr, Anne Cathrine; Wismann, Pernille

    2015-01-01

    The signaling capacity of seven-transmembrane/G-protein-coupled receptors (7TM/GPCRs) can be regulated through ligand-mediated receptor trafficking. Classically, the recycling of internalized receptors is associated with resensitization, whereas receptor degradation terminates signaling. We have......) and glucagon (GCGR) receptors. The interaction and cross-talk between coexpressed receptors is a wide phenomenon of the 7TM/GPCR superfamily. Numerous reports show functional consequences for signaling and trafficking of the involved receptors. On the basis of the high structural similarity and tissue...... coexpression, we here investigated the potential cross-talk between GLP-1R and GIPR or GCGR in both trafficking and signaling pathways. Using a real-time time-resolved FRET-based internalization assay, we show that GLP-1R, GIPR, and GCGR internalize with differential properties. Remarkably, upon coexpression...

  15. Sequence and expression pattern of a novel human orphan G-protein-coupled receptor, GPRC5B, a family C receptor with a short amino-terminal domain

    DEFF Research Database (Denmark)

    Bräuner-Osborne, Hans; Krogsgaard-Larsen, P

    2000-01-01

    Query of GenBank with the amino acid sequence of human metabotropic glutamate receptor subtype 2 (mGluR2) identified a predicted gene product of unknown function on BAC clone CIT987SK-A-69G12 (located on chromosome band 16p12) as a homologous protein. The transcript, entitled GPRC5B, was cloned f...... from an expressed sequence tag clone that contained the entire open reading frame of the transcript encoding a protein of 395 amino acids. Analysis of the protein sequence reveal that GPRC5B contains a signal peptide and seven transmembrane alpha-helices, which is a hallmark of G...

  16. New functions and signaling mechanisms for the class of adhesion G protein-coupled receptors

    DEFF Research Database (Denmark)

    Liebscher, Ines; Ackley, Brian; Araç, Demet

    2014-01-01

    The class of adhesion G protein-coupled receptors (aGPCRs), with 33 human homologs, is the second largest family of GPCRs. In addition to a seven-transmembrane α-helix-a structural feature of all GPCRs-the class of aGPCRs is characterized by the presence of a large N-terminal extracellular region....... In addition, all aGPCRs but one (GPR123) contain a GPCR autoproteolysis-inducing (GAIN) domain that mediates autoproteolytic cleavage at the GPCR autoproteolysis site motif to generate N- and a C-terminal fragments (NTF and CTF, respectively) during protein maturation. Subsequently, the NTF and CTF...

  17. Association between the melatonin receptor 1B gene polymorphism on the risk of type 2 diabetes, impaired glucose regulation: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Qing Xia

    Full Text Available BACKGROUND: Melatonin receptor 1B (MTNR1B belongs to the seven-transmembrane G protein-coupled receptor superfamily involved in insulin secretion, which has attracted considerable attention as a candidate gene for type 2 diabetes (T2D since it was first identified as a loci associated with fasting plasma glucose level through genome wide association approach. The relationship between MTNR1B and T2D has been reported in various ethnic groups. The aim of this study was to consolidate and summarize published data on the potential of MTNR1B polymorphisms in T2D risk prediction. METHODS: PubMed, EMBASE, ISI web of science and the CNKI databases were systematically searched to identify relevant studies. Odds ratios (ORs and 95% confidence intervals (95% CIs were calculated. Heterogeneity and publication bias were also tested. RESULTS: A total of 23 studies involving 172,963 subjects for two common polymorphisms (rs10830963, rs1387153 on MTNR1B were included. An overall random effects per-allele OR of 1.05 (95% CI: 1.02-1.08; P<10(-4 and 1.04 (95% CI: 0.98-1.10; P = 0.20 were found for the two variants respectively. Similar results were also observed using dominant or recessive genetic model. There was strong evidence of heterogeneity, which largely disappeared after stratification by ethnicity. Significant results were found in Caucasians when stratified by ethnicity; while no significant associations were observed in East Asians and South Asians. Besides, we found that the rs10830963 polymorphism is a risk factor associated with increased impaired glucose regulation susceptibility. CONCLUSIONS: This meta-analysis demonstrated that the rs10830963 polymorphism is a risk factor for developing impaired glucose regulation and T2D.

  18. [GPCRs heterodimerization: a new way towards the discovery of function for the orphan receptors?].

    Science.gov (United States)

    Levoye, Angélique; Jockers, Ralf

    2007-01-01

    G protein-coupled receptors (GPCRs), also called seven transmembrane domain (7TM) proteins, represent the largest family of cell surface receptors. GPCRs control a variety of physiological processes, are involved in multiple diseases and are major drug targets. Despite a vast effort of academic and industrial research, more than one hundred receptors remain orphans. These orphan GPCRs offer a great potential for drug discovery, as almost 60% of currently prescribed drugs target GPCRs. Deorphenization strategies have concentrated mainly on the identification of the natural ligands of these proteins. Recent advances have shown that orphan GPCRs, similar to orphan nuclear receptors, can regulate the function of non-orphan receptors by heterodimerization. These findings not only help to better understand the extraordinary diversity of GPCRs, but also open new perspectives for the identification of the function of these orphan receptors that hold great therapeutic potential.

  19. TRV0109101, a G Protein-Biased Agonist of the µ-Opioid Receptor, Does Not Promote Opioid-Induced Mechanical Allodynia following Chronic Administration.

    Science.gov (United States)

    Koblish, Michael; Carr, Richard; Siuda, Edward R; Rominger, David H; Gowen-MacDonald, William; Cowan, Conrad L; Crombie, Aimee L; Violin, Jonathan D; Lark, Michael W

    2017-08-01

    Prescription opioids are a mainstay in the treatment of acute moderate to severe pain. However, chronic use leads to a host of adverse consequences including tolerance and opioid-induced hyperalgesia (OIH), leading to more complex treatment regimens and diminished patient compliance. Patients with OIH paradoxically experience exaggerated nociceptive responses instead of pain reduction after chronic opioid usage. The development of OIH and tolerance tend to occur simultaneously and, thus, present a challenge when studying the molecular mechanisms driving each phenomenon. We tested the hypothesis that a G protein-biased µ -opioid peptide receptor (MOPR) agonist would not induce symptoms of OIH, such as mechanical allodynia, following chronic administration. We observed that the development of opioid-induced mechanical allodynia (OIMA), a model of OIH, was absent in β -arrestin1 -/- and β -arrestin2 -/- mice in response to chronic administration of conventional opioids such as morphine, oxycodone and fentanyl, whereas tolerance developed independent of OIMA. In agreement with the β -arrestin knockout mouse studies, chronic administration of TRV0109101, a G protein-biased MOPR ligand and structural analog of oliceridine, did not promote the development of OIMA but did result in drug tolerance. Interestingly, following induction of OIMA by morphine or fentanyl, TRV0109101 was able to rapidly reverse allodynia. These observations establish a role for β -arrestins in the development of OIH, independent of tolerance, and suggest that the use of G protein-biased MOPR ligands, such as oliceridine and TRV0109101, may be an effective therapeutic avenue for managing chronic pain with reduced propensity for opioid-induced hyperalgesia. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

  20. Structural optimization and structure-functional selectivity relationship studies of G protein-biased EP2 receptor agonists.

    Science.gov (United States)

    Ogawa, Seiji; Watanabe, Toshihide; Moriyuki, Kazumi; Goto, Yoshikazu; Yamane, Shinsaku; Watanabe, Akio; Tsuboi, Kazuma; Kinoshita, Atsushi; Okada, Takuya; Takeda, Hiroyuki; Tani, Kousuke; Maruyama, Toru

    2016-05-15

    The modification of the novel G protein-biased EP2 agonist 1 has been investigated to improve its G protein activity and develop a better understanding of its structure-functional selectivity relationship (SFSR). The optimization of the substituents on the phenyl ring of 1, followed by the inversion of the hydroxyl group on the cyclopentane moiety led to compound 9, which showed a 100-fold increase in its G protein activity compared with 1 without any increase in β-arrestin recruitment. Furthermore, SFSR studies revealed that the combination of meta and para substituents on the phenyl moiety was crucial to the functional selectivity. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. The Paradigm of G Protein Receptor Transactivation: A Mechanistic Definition and Novel Example

    Directory of Open Access Journals (Sweden)

    Peter J. Little

    2011-01-01

    Full Text Available Seven transmembrane G protein—coupled receptors are among the most common in biology and they transduce cellular signals from a plethora of hormones. As well as their own well-characterized signaling pathways, they can also transactivate tyrosine kinase growth factor receptors to greatly expand their own cellular repertoire of responses. Recent data in vascular smooth muscle cells have expanded the breadth of transactivation to include serine/threonine kinase receptors, specifically the receptor for transforming growth factor beta (TGF-β. Stimulation with endothelin and thrombin leads to the rapid formation of C-terminal phosphorylated Smad2, which is the immediate product of activation of the TGF-β receptor. Additionally, it appears that no definition of transactivation based on mechanism is available, so we have provided a definition involving temporal aspects and the absence of de novo protein synthesis. The phenomenon of transactivation is an important biochemical mechanism and potential drug target in multiple diseases.

  2. Anti-analgesic effect of the mu/delta opioid receptor heteromer revealed by ligand-biased antagonism.

    Directory of Open Access Journals (Sweden)

    Laura Milan-Lobo

    Full Text Available Delta (DOR and mu opioid receptors (MOR can complex as heteromers, conferring functional properties in agonist binding, signaling and trafficking that can differ markedly from their homomeric counterparts. Because of these differences, DOR/MOR heteromers may be a novel therapeutic target in the treatment of pain. However, there are currently no ligands selective for DOR/MOR heteromers, and, consequently, their role in nociception remains unknown. In this study, we used a pharmacological opioid cocktail that selectively activates and stabilizes the DOR/MOR heteromer at the cell surface by blocking its endocytosis to assess its role in antinociception. We found that mice treated chronically with this drug cocktail showed a significant right shift in the ED50 for opioid-mediated analgesia, while mice treated with a drug that promotes degradation of the heteromer did not. Furthermore, promoting degradation of the DOR/MOR heteromer after the right shift in the ED50 had occurred, or blocking signal transduction from the stabilized DOR/MOR heteromer, shifted the ED50 for analgesia back to the left. Taken together, these data suggest an anti-analgesic role for the DOR/MOR heteromer in pain. In conclusion, antagonists selective for DOR/MOR heteromer could provide an avenue for alleviating reduced analgesic response during chronic pain treatment.

  3. A library of 7TM receptor C-terminal tails - Interactions with the proposed post-endocytic sorting proteins ERM-binding phosphoprotein 50 (EBP50), N-ethylmaleimide-sensitive factor (NSF), sorting nexin 1 (SNX1), and G protein-coupled receptor-associated sorting protein (GASP)

    DEFF Research Database (Denmark)

    Heydorn, A.; Sondergaard, B.P.; Ersbøll, Bjarne Kjær

    2004-01-01

    Adaptor and scaffolding proteins determine the cellular targeting, the spatial, and thereby the functional association of G protein-coupled seven-transmembrane receptors with co-receptors, transducers, and downstream effectors and the adaptors determine post-signaling events such as receptor...... only a single receptor tail, i.e. the beta(2)-adrenergic receptor, whereas N-ethylmaleimide-sensitive factor bound 11 of the tail-fusion proteins. Of the two proteins proposed to target receptors for lysosomal degradation, sorting nexin 1 (SNX1) bound 10 and the C-terminal domain of G protein...... the expected nanomolar affinities for interaction with SNX1. Truncations of the NK1 receptor revealed that an extended binding epitope is responsible for the interaction with both SNX1 and G protein-coupled receptor-associated sorting protein as well as with N-ethylmaleimide-sensitive factor. It is concluded...

  4. A library of 7TM receptor C-terminal tails. Interactions with the proposed post-endocytic sorting proteins ERM-binding phosphoprotein 50 (EBP50), N-ethylmaleimide-sensitive factor (NSF), sorting nexin 1 (SNX1), and G protein-coupled receptor-associated sorting protein (GASP)

    DEFF Research Database (Denmark)

    Heydorn, Arne; Søndergaard, Birgitte P; Ersbøll, Bjarne

    2004-01-01

    Adaptor and scaffolding proteins determine the cellular targeting, the spatial, and thereby the functional association of G protein-coupled seven-transmembrane receptors with co-receptors, transducers, and downstream effectors and the adaptors determine post-signaling events such as receptor...... only a single receptor tail, i.e. the beta(2)-adrenergic receptor, whereas N-ethylmaleimide-sensitive factor bound 11 of the tail-fusion proteins. Of the two proteins proposed to target receptors for lysosomal degradation, sorting nexin 1 (SNX1) bound 10 and the C-terminal domain of G protein...... the expected nanomolar affinities for interaction with SNX1. Truncations of the NK(1) receptor revealed that an extended binding epitope is responsible for the interaction with both SNX1 and G protein-coupled receptor-associated sorting protein as well as with N-ethylmaleimide-sensitive factor. It is concluded...

  5. Two distinct CXC chemokine receptors (CXCR3 and CXCR4) from the big-belly seahorse Hippocampus abdominalis: Molecular perspectives and immune defensive role upon pathogenic stress.

    Science.gov (United States)

    Priyathilaka, Thanthrige Thiunuwan; Oh, Minyoung; Bathige, S D N K; De Zoysa, Mahanama; Lee, Jehee

    2017-06-01

    CXC chemokine receptor 3 (CXCR3) and 4 (CXCR4) are members of the seven transmembrane G protein coupled receptor family, involved in pivotal physiological functions. In this study, seahorse CXCR3 and CXCR4 (designated as HaCXCR3 and HaCXCR4) cDNA sequences were identified from the transcriptome library and subsequently molecularly characterized. HaCXCR3 and HaCXCR4 encoded 363 and 373 amino acid long polypeptides, respectively. The HaCXCR3 and HaCXCR4 deduced proteins have typical structural features of chemokine receptors, including seven transmembrane domains and a G protein coupled receptors family 1 profile with characteristic DRY motifs. Amino acid sequence comparison and phylogenetic analysis of these two CXC chemokine receptors revealed a close relationship to their corresponding teleost counterparts. Quantitative real time PCR analysis revealed that HaCXCR3 and HaCXCR4 were ubiquitously expressed in all the tested tissues, with highest expression levels in blood cells. The seahorse blood cells and kidney HaCXCR3 and HaCXCR4 mRNA expressions were differently modulated when challenged with Edwardsiella tarda, Streptococcus iniae, lipopolysaccharide, and polyinosinic:polycytidylic acid, confirming their involvement in post immune responses. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Key interactions by conserved polar amino acids located at the transmembrane helical boundaries in Class B GPCRs modulate activation, effector specificity and biased signalling in the glucagon-like peptide-1 receptor

    OpenAIRE

    Wootten, Denise; Reynolds, Christopher A.; Smith, Kevin J.; Mobarec, Juan C.; Furness, Sebastian G.B.; Miller, Laurence J.; Christopoulos, Arthur; Sexton, Patrick M.

    2016-01-01

    Class B GPCRs can activate multiple signalling effectors with the potential to exhibit biased agonism in response to ligand stimulation. Previously, we highlighted key TM domain polar amino acids that were crucial for the function of the GLP-1 receptor, a key therapeutic target for diabetes and obesity. Using a combination of mutagenesis, pharmacological characterisation, mathematical and computational molecular modelling, this study identifies additional highly conserved polar residues locat...

  7. Key interactions by conserved polar amino acids located at the transmembrane helical boundaries in Class B GPCRs modulate activation, effector specificity and biased signalling in the glucagon-like peptide-1 receptor.

    Science.gov (United States)

    Wootten, Denise; Reynolds, Christopher A; Smith, Kevin J; Mobarec, Juan C; Furness, Sebastian G B; Miller, Laurence J; Christopoulos, Arthur; Sexton, Patrick M

    2016-10-15

    Class B GPCRs can activate multiple signalling effectors with the potential to exhibit biased agonism in response to ligand stimulation. Previously, we highlighted key TM domain polar amino acids that were crucial for the function of the GLP-1 receptor, a key therapeutic target for diabetes and obesity. Using a combination of mutagenesis, pharmacological characterisation, mathematical and computational molecular modelling, this study identifies additional highly conserved polar residues located towards the TM helical boundaries of Class B GPCRs that are important for GLP-1 receptor stability and/or controlling signalling specificity and biased agonism. This includes (i) three positively charged residues (R3.30 227 , K4.64 288 , R5.40 310 ) located at the extracellular boundaries of TMs 3, 4 and 5 that are predicted in molecular models to stabilise extracellular loop 2, a crucial domain for ligand affinity and receptor activation; (ii) a predicted hydrogen bond network between residues located in TMs 2 (R2.46 176 ), 6 (R6.37 348 ) and 7 (N7.61 406 and E7.63 408 ) at the cytoplasmic face of the receptor that is important for stabilising the inactive receptor and directing signalling specificity, (iii) residues at the bottom of TM 5 (R5.56 326 ) and TM6 (K6.35 346 and K6.40 351 ) that are crucial for receptor activation and downstream signalling; (iv) residues predicted to be involved in stabilisation of TM4 (N2.52 182 and Y3.52 250 ) that also influence cell signalling. Collectively, this work expands our understanding of peptide-mediated signalling by the GLP-1 receptor. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  8. Sympathetic bias.

    Science.gov (United States)

    Levy, David M; Peart, Sandra J

    2008-06-01

    We wish to deal with investigator bias in a statistical context. We sketch how a textbook solution to the problem of "outliers" which avoids one sort of investigator bias, creates the temptation for another sort. We write down a model of the approbation seeking statistician who is tempted by sympathy for client to violate the disciplinary standards. We give a simple account of one context in which we might expect investigator bias to flourish. Finally, we offer tentative suggestions to deal with the problem of investigator bias which follow from our account. As we have given a very sparse and stylized account of investigator bias, we ask what might be done to overcome this limitation.

  9. PHARMACOGENOMICS OF PROSTAGLANDIN AND LEUKOTRIENE RECEPTORS

    Directory of Open Access Journals (Sweden)

    José Antonio Cornejo-García

    2016-09-01

    Full Text Available Individual genetic background together with environmental effects are thought to be behind many human complex diseases. A number of genetic variants, mainly single nucleotide polymorphisms (SNPs, have been shown to be associated with various pathological and inflammatory conditions, representing potential therapeutic targets. Prostaglandins (PTGs and leukotrienes (LTs are eicosanoids derived from arachidonic acid and related polyunsaturated fatty acids that participate in both normal homeostasis and inflammatory conditions. These bioactive lipid mediators are synthesised through two major multistep enzymatic pathways: PTGs by cyclooxygenase and LTs by 5-lipoxygenase. The main physiological effects of PTGs include vasodilation and vascular leakage (PTGE2; mast cell maturation, eosinophil recruitment and allergic responses (PTGD2; vascular and respiratory smooth muscle contraction (PTGF2, and inhibition of platelet aggregation (PTGI2. LTB4 is mainly involved in neutrophil recruitment, vascular leakage, and epithelial barrier function, whereas cysteinyl LTs (CysLTs (LTC4, LTD4 and LTE4 induce bronchoconstriction and neutrophil extravasation, and also participate in vascular leakage. PTGs and LTs exert their biological functions by binding to cognate receptors, which belong to the seven transmembrane, G protein-coupled receptor superfamily. SNPs in genes encoding these receptors may influence their functionality and have a role in disease susceptibility and drug treatment response. In this review we summarize SNPs in PTGs and LTs receptors and their relevance in human diseases. We also provide information on gene expression. Finally, we speculate on future directions for this topic.

  10. The Cannabinoid Receptor CB1 Modulates the Signaling Properties of the Lysophosphatidylinositol Receptor GPR55*

    Science.gov (United States)

    Kargl, Julia; Balenga, Nariman; Parzmair, Gerald P.; Brown, Andrew J.; Heinemann, Akos; Waldhoer, Maria

    2012-01-01

    The G protein-coupled receptor (GPCR) 55 (GPR55) and the cannabinoid receptor 1 (CB1R) are co-expressed in many tissues, predominantly in the central nervous system. Seven transmembrane spanning (7TM) receptors/GPCRs can form homo- and heteromers and initiate distinct signaling pathways. Recently, several synthetic CB1 receptor inverse agonists/antagonists, such as SR141716A, AM251, and AM281, were reported to activate GPR55. Of these, SR141716A was marketed as a promising anti-obesity drug, but was withdrawn from the market because of severe side effects. Here, we tested whether GPR55 and CB1 receptors are capable of (i) forming heteromers and (ii) whether such heteromers could exhibit novel signaling patterns. We show that GPR55 and CB1 receptors alter each others signaling properties in human embryonic kidney (HEK293) cells. We demonstrate that the co-expression of FLAG-CB1 receptors in cells stably expressing HA-GPR55 specifically inhibits GPR55-mediated transcription factor activation, such as nuclear factor of activated T-cells and serum response element, as well as extracellular signal-regulated kinases (ERK1/2) activation. GPR55 and CB1 receptors can form heteromers, but the internalization of both receptors is not affected. In addition, we observe that the presence of GPR55 enhances CB1R-mediated ERK1/2 and nuclear factor of activated T-cell activation. Our data provide the first evidence that GPR55 can form heteromers with another 7TM/GPCR and that this interaction with the CB1 receptor has functional consequences in vitro. The GPR55-CB1R heteromer may play an important physiological and/or pathophysiological role in tissues endogenously co-expressing both receptors. PMID:23161546

  11. receptores

    Directory of Open Access Journals (Sweden)

    Salete Regina Daronco Benetti

    2006-01-01

    Full Text Available Se trata de un estudio etnográfico, que tuvo lo objetivo de interpretar el sistema de conocimiento y del significado atribuidos a la sangre referente a la transfusión sanguínea por los donadores y receptores de un banco de sangre. Para la colecta de las informaciones se observaron los participantes y la entrevista etnográfica se realizó el análisis de dominio, taxonómicos y temáticos. Los dominios culturales fueron: la sangre es vida: fuente de vida y alimento valioso; creencias religiosas: fuentes simbólicas de apoyos; donación sanguínea: un gesto colaborador que exige cuidarse, gratifica y trae felicidad; donación sanguínea: fuente simbólica de inseguridad; estar enfermo es una condición para realizar transfusión sanguínea; transfusión sanguínea: esperanza de vida; Creencias populares: transfusión sanguínea como riesgo para la salud; donadores de sangre: personas benditas; donar y recibir sangre: como significado de felicidad. Temática: “líquido precioso que origina, sostiene, modifica la vida, provoca miedo e inseguridad”.

  12. A Hydrogen-Bonded Polar Network in the Core of the Glucagon-Like Peptide-1 Receptor Is a Fulcrum for Biased Agonism: Lessons from Class B Crystal Structures.

    Science.gov (United States)

    Wootten, Denise; Reynolds, Christopher A; Koole, Cassandra; Smith, Kevin J; Mobarec, Juan C; Simms, John; Quon, Tezz; Coudrat, Thomas; Furness, Sebastian G B; Miller, Laurence J; Christopoulos, Arthur; Sexton, Patrick M

    2016-03-01

    The glucagon-like peptide 1 (GLP-1) receptor is a class B G protein-coupled receptor (GPCR) that is a key target for treatments for type II diabetes and obesity. This receptor, like other class B GPCRs, displays biased agonism, though the physiologic significance of this is yet to be elucidated. Previous work has implicated R2.60(190), N3.43(240), Q7.49(394), and H6.52(363) as key residues involved in peptide-mediated biased agonism, with R2.60(190), N3.43(240), and Q7.49(394) predicted to form a polar interaction network. In this study, we used novel insight gained from recent crystal structures of the transmembrane domains of the glucagon and corticotropin releasing factor 1 (CRF1) receptors to develop improved models of the GLP-1 receptor that predict additional key molecular interactions with these amino acids. We have introduced E6.53(364)A, N3.43(240)Q, Q7.49(394)N, and N3.43(240)Q/Q7.49(394)N mutations to probe the role of predicted H-bonding and charge-charge interactions in driving cAMP, calcium, or extracellular signal-regulated kinase (ERK) signaling. A polar interaction between E6.53(364) and R2.60(190) was predicted to be important for GLP-1- and exendin-4-, but not oxyntomodulin-mediated cAMP formation and also ERK1/2 phosphorylation. In contrast, Q7.49(394), but not R2.60(190)/E6.53(364) was critical for calcium mobilization for all three peptides. Mutation of N3.43(240) and Q7.49(394) had differential effects on individual peptides, providing evidence for molecular differences in activation transition. Collectively, this work expands our understanding of peptide-mediated signaling from the GLP-1 receptor and the key role that the central polar network plays in these events. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  13. Non-Neuronal Functions of the M2 Muscarinic Acetylcholine Receptor

    Directory of Open Access Journals (Sweden)

    Ritva Tikkanen

    2013-04-01

    Full Text Available Acetylcholine is an important neurotransmitter whose effects are mediated by two classes of receptors. The nicotinic acetylcholine receptors are ion channels, whereas the muscarinic receptors belong to the large family of G protein coupled seven transmembrane helix receptors. Beyond its function in neuronal systems, it has become evident that acetylcholine also plays an important role in non-neuronal cells such as epithelial and immune cells. Furthermore, many cell types in the periphery are capable of synthesizing acetylcholine and express at least some of the receptors. In this review, we summarize the non-neuronal functions of the muscarinic acetylcholine receptors, especially those of the M2 muscarinic receptor in epithelial cells. We will review the mechanisms of signaling by the M2 receptor but also the cellular trafficking and ARF6 mediated endocytosis of this receptor, which play an important role in the regulation of signaling events. In addition, we provide an overview of the M2 receptor in human pathological conditions such as autoimmune diseases and cancer.

  14. Biased and Constitutive Signaling in the CC-Chemokine Receptor CCR5 by manipulating the Interface between Transmembrane Helix 6 and 7

    DEFF Research Database (Denmark)

    Steen, Anne; Thiele, Stefanie; Guo, Dong

    2013-01-01

    The equilibrium state of CCR5 is manipulated here toward either activation or inactivation by introduction of single amino acid substitutions in the transmembrane domains (TMs) 6 and 7. Insertion of a steric hindrance mutation in the center of TM7 (G286F in position VII:09/7.42) resulted in biase...

  15. Two seven-transmembrane domain MILDEW RESISTANCE LOCUS O proteins cofunction in Arabidopsis root thigmomorphogenesis.

    Science.gov (United States)

    Chen, Zhongying; Noir, Sandra; Kwaaitaal, Mark; Hartmann, H Andreas; Wu, Ming-Jing; Mudgil, Yashwanti; Sukumar, Poornima; Muday, Gloria; Panstruga, Ralph; Jones, Alan M

    2009-07-01

    Directional root expansion is governed by nutrient gradients, positive gravitropism and hydrotropism, negative phototropism and thigmotropism, as well as endogenous oscillations in the growth trajectory (circumnutation). Null mutations in phylogenetically related Arabidopsis thaliana genes MILDEW RESISTANCE LOCUS O 4 (MLO4) and MLO11, encoding heptahelical, plasma membrane-localized proteins predominantly expressed in the root tip, result in aberrant root thigmomorphogenesis. mlo4 and mlo11 mutant plants show anisotropic, chiral root expansion manifesting as tightly curled root patterns upon contact with solid surfaces. The defect in mlo4 and mlo11 mutants is nonadditive and dependent on light and nutrients. Genetic epistasis experiments demonstrate that the mutant phenotype is independently modulated by the Gbeta subunit of the heterotrimeric G-protein complex. Analysis of expressed chimeric MLO4/MLO2 proteins revealed that the C-terminal domain of MLO4 is necessary but not sufficient for MLO4 action in root thigmomorphogenesis. The expression of the auxin efflux carrier fusion, PIN1-green fluorescent protein, the pattern of auxin-induced gene expression, and acropetal as well as basipetal auxin transport are altered at the root tip of mlo4 mutant seedlings. Moreover, addition of auxin transport inhibitors or the loss of EIR1/AGR1/PIN2 function abolishes root curling of mlo4, mlo11, and wild-type seedlings. These results demonstrate that the exaggerated root curling phenotypes of the mlo4 and mlo11 mutants depend on auxin gradients and suggest that MLO4 and MLO11 cofunction as modulators of touch-induced root tropism.

  16. Journal bias or author bias?

    Science.gov (United States)

    Harris, Ian

    2016-01-01

    I read with interest the comment by Mark Wilson in the Indian Journal of Medical Ethics regarding bias and conflicts of interest in medical journals. Wilson targets one journal (the New England Journal of Medicine: NEJM) and one particular "scandal" to make his point that journals' decisions on publication are biased by commercial conflicts of interest (CoIs). It is interesting that he chooses the NEJM which, by his own admission, had one of the strictest CoI policies and had published widely on this topic. The feeling is that if the NEJM can be guilty, they can all be guilty.

  17. Activation of the CXCR3 chemokine receptor through anchoring of a small molecule chelator ligand between TM-III, -IV, and -VI

    DEFF Research Database (Denmark)

    Rosenkilde, Mette M; Andersen, Michael B; Nygaard, Rie

    2006-01-01

    modeling and molecular simulations combined with mutational analysis indicated that the metal ion site-anchored chelators act as agonists by establishing an aromatic-aromatic, second-site interaction with TyrVI:16 on the inner face of TM-VI. It is noteworthy that this interaction required......Seven transmembrane segment (7TM) receptors are activated through a common, still rather unclear molecular mechanism by a variety of chemical messengers ranging from monoamines to large proteins. By introducing a His residue at position III:05 in the CXCR3 receptor a metal ion site was built...... between the extracellular ends of transmembrane (TM) III and TM-IV to anchor aromatic chelators at a location corresponding to the presumed binding pocket for adrenergic receptor agonists. In this construct, free metal ions had no agonistic effect in accordance with the optimal geometry of the metal ion...

  18. Biased Supervision

    OpenAIRE

    Josse Delfgaauw; Michiel Souverijn

    2014-01-01

    markdownabstract__Abstract__ When verifiable performance measures are imperfect, organizations often resort to subjective performance pay. This may give supervisors the power to direct employees towards tasks that mainly benefit the supervisor rather than the organization. We cast a principal-supervisor-agent model in a multitask setting, where the supervisor has an intrinsic preference towards specific tasks. We show that subjective performance pay based on evaluation by a biased supervisor ...

  19. Molecular cloning of a functional allatostatin gut/brain receptor and an allatostatin preprohormone from the silkworm Bombyx mori

    DEFF Research Database (Denmark)

    Secher, Thomas; Lenz, C; Cazzamali, G

    2001-01-01

    in the DAR-1 and DAR-2 genes, showing that the three receptors are not only structurally but also evolutionarily related. Furthermore, we have cloned a Bombyx allatostatin preprohormone that contains eight different A-type allatostatins. Chinese hamster ovary cells permanently transfected with BAR DNA react......The cockroach-type or A-type allatostatins are inhibitory insect neuropeptides with the C-terminal sequence Tyr/Phe-X-Phe-Gly-Leu-NH(2). Here, we have cloned an A-type allatostatin receptor from the silkworm Bombyx mori (BAR). BAR is 361 amino acid residues long, has seven transmembrane domains....... Northern blots and quantitative reverse transcriptase-polymerase chain reaction of different larval tissues show that BAR mRNA is mainly expressed in the gut and to a much lesser extent in the brain. To our knowledge, this is the first report on the molecular cloning and functional expression of an insect...

  20. Adrenergic Agonists Bind to Adrenergic-Receptor-Like Regions of the Mu Opioid Receptor, Enhancing Morphine and Methionine-Enkephalin Binding: A New Approach to “Biased Opioids”?

    Science.gov (United States)

    Turke, Miah; Subhramanyam, Udaya K. Tiruttani; Churchill, Beth; Labahn, Joerg

    2018-01-01

    Extensive evidence demonstrates functional interactions between the adrenergic and opioid systems in a diversity of tissues and organs. While some effects are due to receptor and second messenger cross-talk, recent research has revealed an extracellular, allosteric opioid binding site on adrenergic receptors that enhances adrenergic activity and its duration. The present research addresses whether opioid receptors may have an equivalent extracellular, allosteric adrenergic binding site that has similar enhancing effects on opioid binding. Comparison of adrenergic and opioid receptor sequences revealed that these receptors share very significant regions of similarity, particularly in some of the extracellular and transmembrane regions associated with adrenergic binding in the adrenergic receptors. Five of these shared regions from the mu opioid receptor (muOPR) were synthesized as peptides and tested for binding to adrenergic, opioid and control compounds using ultraviolet spectroscopy. Adrenergic compounds bound to several of these muOPR peptides with low micromolar affinity while acetylcholine, histamine and various adrenergic antagonists did not. Similar studies were then conducted with purified, intact muOPR with similar results. Combinations of epinephrine with methionine enkephalin or morphine increased the binding of both by about half a log unit. These results suggest that muOPR may be allosterically enhanced by adrenergic agonists. PMID:29342106

  1. Adrenergic Agonists Bind to Adrenergic-Receptor-Like Regions of the Mu Opioid Receptor, Enhancing Morphine and Methionine-Enkephalin Binding: A New Approach to “Biased Opioids”?

    Directory of Open Access Journals (Sweden)

    Robert Root-Bernstein

    2018-01-01

    Full Text Available Extensive evidence demonstrates functional interactions between the adrenergic and opioid systems in a diversity of tissues and organs. While some effects are due to receptor and second messenger cross-talk, recent research has revealed an extracellular, allosteric opioid binding site on adrenergic receptors that enhances adrenergic activity and its duration. The present research addresses whether opioid receptors may have an equivalent extracellular, allosteric adrenergic binding site that has similar enhancing effects on opioid binding. Comparison of adrenergic and opioid receptor sequences revealed that these receptors share very significant regions of similarity, particularly in some of the extracellular and transmembrane regions associated with adrenergic binding in the adrenergic receptors. Five of these shared regions from the mu opioid receptor (muOPR were synthesized as peptides and tested for binding to adrenergic, opioid and control compounds using ultraviolet spectroscopy. Adrenergic compounds bound to several of these muOPR peptides with low micromolar affinity while acetylcholine, histamine and various adrenergic antagonists did not. Similar studies were then conducted with purified, intact muOPR with similar results. Combinations of epinephrine with methionine enkephalin or morphine increased the binding of both by about half a log unit. These results suggest that muOPR may be allosterically enhanced by adrenergic agonists.

  2. Monoclonal Antibodies to the Thyrotropin Receptor

    Directory of Open Access Journals (Sweden)

    Takao Ando

    2005-01-01

    Full Text Available The thyrotropin receptor (TSHR is a seven transmembrane G-protein linked glycoprotein expressed on the thyroid cell surface and which, under the regulation of TSH, controls the production and secretion of thyroid hormone from the thyroid gland. This membrane protein is also a major target antigen in the autoimmune thyroid diseases. In Graves' disease, autoantibodies to the TSHR (TSHR-Abs stimulate the TSHR to produce thyroid hormone excessively. In autoimmune thyroid failure, some patients exhibit TSHR-Abs which block TSH action on the receptor. There have been many attempts to generate human stimulating TSHR-mAbs, but to date, only one pathologically relevant human stimulating TSHR-mAb has been isolated. Most mAbs to the TSHR have been derived from rodents immunized with TSHR antigen from bacteria or insect cells. These antigens lacked the native conformation of the TSHR and the resulting mAbs were exclusively blocking or neutral TSHR-mAbs. However, mAbs raised against intact native TSHR antigen have included stimulating mAbs. One such stimulating mAb has demonstrated a number of differences in its regulation of TSHR post-translational processing. These differences are likely to be reflective of TSHR-Abs seen in Graves' disease.

  3. Localization of the fourth membrane spanning domain as a ligand binding site in the human platelet α2-adrenergic receptor

    International Nuclear Information System (INIS)

    Matsui, Hiroaki; Lefkowitz, R.J.; Caron, M.G.; Regan, J.W.

    1989-01-01

    The human platelet α 2 -adrenergic receptor is an integral membrane protein which binds epinephrine. The gene for this receptor has been cloned, and the primary structure is thus known. A model of its secondary structure predicts that the receptor has seven transmembrane spanning domains. By covalent labeling and peptide mapping, the authors have identified a region of the receptor that is directly involved with ligand binding. Partially purified preparations of the receptor were covalently radiolabeled with either of two specific photoaffinity ligands: [ 3 H]SKF 102229 (an antagonist) or p-azido[ 3 H]clonidine (an agonist). The radiolabeled receptors were then digested with specific endopeptidases, and peptides containing the covalently bound radioligands were identified. Lysylendopeptidase treatment of [ 3 H]SKF 102229 labeled receptor yielded one peptide of M r 2400 as the product of a complete digest. Endopeptidase Arg-C gave a labeled peptide of M r 4000, which was further digested to the M r 2400 peptide by additional treatment with lysylendopeptidase. Using p-azido[ 3 H]clonidine-labeled receptor, a similar M r 2400 peptide was obtained by lysylendopeptidase cleavage. This M r 2400 peptide corresponds to the fourth transmembrane spanning domain of the receptor. These data suggest that this region forms part of the ligand binding domain of the human platelet α 2 -adrenergic receptor

  4. Development of 7TM receptor-ligand complex models using ligand-biased, semi-empirical helix-bundle repacking in torsion space: application to the agonist interaction of the human dopamine D2 receptor.

    Science.gov (United States)

    Malo, Marcus; Persson, Ronnie; Svensson, Peder; Luthman, Kristina; Brive, Lars

    2013-03-01

    Prediction of 3D structures of membrane proteins, and of G-protein coupled receptors (GPCRs) in particular, is motivated by their importance in biological systems and the difficulties associated with experimental structure determination. In the present study, a novel method for the prediction of 3D structures of the membrane-embedded region of helical membrane proteins is presented. A large pool of candidate models are produced by repacking of the helices of a homology model using Monte Carlo sampling in torsion space, followed by ranking based on their geometric and ligand-binding properties. The trajectory is directed by weak initial restraints to orient helices towards the original model to improve computation efficiency, and by a ligand to guide the receptor towards a chosen conformational state. The method was validated by construction of the β1 adrenergic receptor model in complex with (S)-cyanopindolol using bovine rhodopsin as template. In addition, models of the dopamine D2 receptor were produced with the selective and rigid agonist (R)-N-propylapomorphine ((R)-NPA) present. A second quality assessment was implemented by evaluating the results from docking of a library of 29 ligands with known activity, which further discriminated between receptor models. Agonist binding and recognition by the dopamine D2 receptor is interpreted using the 3D structure model resulting from the approach. This method has a potential for modeling of all types of helical transmembrane proteins for which a structural template with sequence homology sufficient for homology modeling is not available or is in an incorrect conformational state, but for which sufficient empirical information is accessible.

  5. An automated system for the analysis of G protein-coupled receptor transmembrane binding pockets: alignment, receptor-based pharmacophores, and their application.

    Science.gov (United States)

    Kratochwil, Nicole A; Malherbe, Pari; Lindemann, Lothar; Ebeling, Martin; Hoener, Marius C; Mühlemann, Andreas; Porter, Richard H P; Stahl, Martin; Gerber, Paul R

    2005-01-01

    G protein-coupled receptors (GPCRs) share a common architecture consisting of seven transmembrane (TM) domains. Various lines of evidence suggest that this fold provides a generic binding pocket within the TM region for hosting agonists, antagonists, and allosteric modulators. Here, a comprehensive and automated method allowing fast analysis and comparison of these putative binding pockets across the entire GPCR family is presented. The method relies on a robust alignment algorithm based on conservation indices, focusing on pharmacophore-like relationships between amino acids. Analysis of conservation patterns across the GPCR family and alignment to the rhodopsin X-ray structure allows the extraction of the amino acids lining the TM binding pocket in a so-called ligand binding pocket vector (LPV). In a second step, LPVs are translated to simple 3D receptor pharmacophore models, where each amino acid is represented by a single spherical pharmacophore feature and all atomic detail is omitted. Applications of the method include the assessment of selectivity issues, support of mutagenesis studies, and the derivation of rules for focused screening to identify chemical starting points in early drug discovery projects. Because of the coarseness of this 3D receptor pharmacophore model, however, meaningful scoring and ranking procedures of large sets of molecules are not justified. The LPV analysis of the trace amine-associated receptor family and its experimental validation is discussed as an example. The value of the 3D receptor model is demonstrated for a class C GPCR family, the metabotropic glutamate receptors.

  6. Biased Gs Versus Gq Proteins and β-Arrestin Signaling in the NK1 Receptor Determined by Interactions in the Water Hydrogen Bond Network

    DEFF Research Database (Denmark)

    Valentin-Hansen, Louise; Frimurer, Thomas M; Mokrosinski, Jacek

    2015-01-01

    X-ray structures, molecular dynamics simulations, and mutational analysis have previously indicated that an extended water hydrogen bond network between trans-membranes I-III, VI, and VII constitutes an allosteric interface essential for stabilizing different active and inactive helical...... of the highly conserved AspII:10 (2.50). Here, we find that this GluII:10 occupies the space of a putative allosteric modulating Na(+) ion and makes direct inter-helical interactions in particular with SerIII:15 (3.39) and AsnVII:16 (7.49) of the NPXXY motif. Mutational changes in the interface between GluII:10....... It is concluded that the interface between position II:10 (2.50), III:15 (3.39), and VII:16 (7.49) in the center of the water hydrogen bond network constitutes a focal point for fine-tuning seven trans-membrane receptor conformations activating different signal transduction pathways....

  7. METHODS FOR RECOMBINANT EXPRESSION AND FUNCTIONAL CHARACTERIZATION OF HUMAN CANNABINOID RECEPTOR CB2

    Directory of Open Access Journals (Sweden)

    Alexei A. Yeliseev

    2013-03-01

    Full Text Available Cannabinoid receptor CB2 is a seven transmembrane-domain integral membrane protein that belongs to a large superfamily of G protein-coupled receptors (GPCR. CB2 is a part of the endocannabinoid system that plays vital role in regulation of immune response, inflammation, pain sensitivity, obesity and other physiological responses. Information about the structure and mechanisms of functioning of this receptor in cell membranes is essential for the rational development of specific pharmaceuticals. Here we review the methodology for recombinant expression, purification, stabilization and biochemical characterization of CB2 suitable for preparation of multi-milligram quantities of functionally active receptor. The biotechnological protocols include expression of the recombinant CB2 in E. coli cells as a fusion with the maltose binding protein, stabilization with a high affinity ligand and a derivative of cholesterol in detergent micelles, efficient purification by tandem affinity chromatography, and reconstitution of the receptor into lipid bilayers. The purified recombinant CB2 receptor is amenable to functional and structural studies including nuclear magnetic resonance spectroscopy and a wide range of biochemical and biophysical techniques.

  8. Delineation of the peptide binding site of the human galanin receptor.

    Science.gov (United States)

    Kask, K; Berthold, M; Kahl, U; Nordvall, G; Bartfai, T

    1996-01-01

    Galanin, a neuroendocrine peptide of 29 amino acids, binds to Gi/Go-coupled receptors to trigger cellular responses. To determine which amino acids of the recently cloned seven-transmembrane domain-type human galanin receptor are involved in the high-affinity binding of the endogenous peptide ligand, we performed a mutagenesis study. Mutation of the His264 or His267 of transmembrane domain VI to alanine, or of Phe282 of transmembrane domain VII to glycine, results in an apparent loss of galanin binding. The substitution of Glu271 to serine in the extracellular loop III of the receptor causes a 12-fold loss in affinity for galanin. We combined the mutagenesis results with data on the pharmacophores (Trp2, Tyr9) of galanin and with molecular modelling of the receptor using bacteriorhodopsin as a model. Based on these studies, we propose a binding site model for the endogenous peptide ligand in the galanin receptor where the N-terminus of galanin hydrogen bonds with Glu271 of the receptor, Trp2 of galanin interacts with the Zn2+ sensitive pair of His264 and His267 of transmembrane domain VI, and Tyr9 of galanin interacts with Phe282 of transmembrane domain VII, while the C-terminus of galanin is pointing towards the N-terminus of th Images PMID:8617199

  9. Cloning of human genes encoding novel G protein-coupled receptors

    Energy Technology Data Exchange (ETDEWEB)

    Marchese, A.; Docherty, J.M.; Heiber, M. [Univ. of Toronto, (Canada)] [and others

    1994-10-01

    We report the isolation and characterization of several novel human genes encoding G protein-coupled receptors. Each of the receptors contained the familiar seven transmembrane topography and most closely resembled peptide binding receptors. Gene GPR1 encoded a receptor protein that is intronless in the coding region and that shared identity (43% in the transmembrane regions) with the opioid receptors. Northern blot analysis revealed that GPR1 transcripts were expressed in the human hippocampus, and the gene was localized to chromosome 15q21.6. Gene GPR2 encoded a protein that most closely resembled an interleukin-8 receptor (51% in the transmembrane regions), and this gene, not expressed in the six brain regions examined, was localized to chromosome 17q2.1-q21.3. A third gene, GPR3, showed identity (56% in the transmembrane regions) with a previously characterized cDNA clone from rat and was localized to chromosome 1p35-p36.1. 31 refs., 5 figs., 1 tab.

  10. Bias against research on gender bias.

    Science.gov (United States)

    Cislak, Aleksandra; Formanowicz, Magdalena; Saguy, Tamar

    2018-01-01

    The bias against women in academia is a documented phenomenon that has had detrimental consequences, not only for women, but also for the quality of science. First, gender bias in academia affects female scientists, resulting in their underrepresentation in academic institutions, particularly in higher ranks. The second type of gender bias in science relates to some findings applying only to male participants, which produces biased knowledge. Here, we identify a third potentially powerful source of gender bias in academia: the bias against research on gender bias. In a bibliometric investigation covering a broad range of social sciences, we analyzed published articles on gender bias and race bias and established that articles on gender bias are funded less often and published in journals with a lower Impact Factor than articles on comparable instances of social discrimination. This result suggests the possibility of an underappreciation of the phenomenon of gender bias and related research within the academic community. Addressing this meta-bias is crucial for the further examination of gender inequality, which severely affects many women across the world.

  11. The role of calcium-sensing receptor and signalling pathways in the pathophysiology in two in vitro models of malignant hypercalcemia: the rat rice H-500 Leydig testis cancer and prostate cancer (PC-3) cells. Expression and regulation of pituitary tumor transforming gene in Leydig testis cancer

    DEFF Research Database (Denmark)

    Tfelt-Hansen, J.

    2008-01-01

    The calcium-sensing receptor (CaR) is a seven transmembrane receptor incorporated into the cell membrane that is sensitive to extracellular calcium and other cations. The finding that the CaR is expressed on cancer cells has opened the door to a new understanding of the role of extracellular...... too many adverse effects on calcium homeostasis. In conclusion, the CaR plays diverse roles in cancer-acting as an inhibitor of cell proliferation in the colon crypt cells giving rise to colon cancer but as a promalignant receptor in most other cancer types, including Leydig cell cancers...... calcium as a promalignant stimulus through the CaR and its signaling apparatus as demonstrated in this thesis. I found, in a model of humoral hypercalcemia of malignancy (HHM), that stimulation of the CaR worsens the promalignant features of the testicular H-500 Leydig cancer cells that were used in my...

  12. Molecular characterization of a rat α2B-adrenergic receptor

    International Nuclear Information System (INIS)

    Zeng, D.; Harrison, J.K.; D'Angelo, D.D.; Barber, C.M.; Tucker, A.L.; Lu, Z.; Lynch, K.R.

    1990-01-01

    α 2 -Adrenergic receptors comprise a heterogeneous population based on pharmacologic and molecular evidence. The authors have isolated a cDNA clone (pRNGα 2 ) encoding a rat α 2 -adrenergic receptor. A rat kidney cDNA library was screened with an oligonucleotide complementary to a highly conserved region found in all biogenic amine receptors described to date. The deduced amino acid sequence displays many features of guanyl nucleotide-binding protein-coupled receptors except it does not have a consensus N-linked glycosylation site near the amino terminus. Membranes prepared from COS cells transfected with pRNGα 2 DNA display high affinity an saturable binding to [ 3 H]rauwolscine. Competition curve data analysis shows that RNGα 2 protein binds to a variety of adrenergic drugs with the following rank order of potency: yohimbine ≥ chlorpromazine > prazosin ≥ clonidine > norepinephrine ≥ oxymetazoline. RNGα 2 RNA accumulates in both rat kidney and neonatal rat lung. When a cysteine residue (Cys-169) that is conserved among all members of the seven-transmembrane-region superfamily is changed to phenylalanine, the RNGα 2 protein fails to bind [ 3 H]rauwolscine after expression in COS cells. They conclude that pRNGα 2 likely represents a cDNA for a rat α 2B -adrenergic receptor

  13. Phosphorylation of G Protein-Coupled Receptors: From the Barcode Hypothesis to the Flute Model.

    Science.gov (United States)

    Yang, Zhao; Yang, Fan; Zhang, Daolai; Liu, Zhixin; Lin, Amy; Liu, Chuan; Xiao, Peng; Yu, Xiao; Sun, Jin-Peng

    2017-09-01

    Seven transmembrane G protein-coupled receptors (GPCRs) are often phosphorylated at the C terminus and on intracellular loops in response to various extracellular stimuli. Phosphorylation of GPCRs by GPCR kinases and certain other kinases can promote the recruitment of arrestin molecules. The arrestins critically regulate GPCR functions not only by mediating receptor desensitization and internalization, but also by redirecting signaling to G protein-independent pathways via interactions with numerous downstream effector molecules. Accumulating evidence over the past decade has given rise to the phospho-barcode hypothesis, which states that ligand-specific phosphorylation patterns of a receptor direct its distinct functional outcomes. Our recent work using unnatural amino acid incorporation and fluorine-19 nuclear magnetic resonance ( 19 F-NMR) spectroscopy led to the flute model, which provides preliminary insight into the receptor phospho-coding mechanism, by which receptor phosphorylation patterns are recognized by an array of phosphate-binding pockets on arrestin and are translated into distinct conformations. These selective conformations are recognized by various effector molecules downstream of arrestin. The phospho-barcoding mechanism enables arrestin to recognize a wide range of phosphorylation patterns of GPCRs, contributing to their diverse functions. Copyright © 2017 by The Author(s).

  14. The Fifth Transmembrane Domain of Angiotensin II Type 1 Receptor Participates in the Formation of the Ligand-binding Pocket and Undergoes a Counterclockwise Rotation upon Receptor Activation*

    Science.gov (United States)

    Domazet, Ivana; Martin, Stéphane S.; Holleran, Brian J.; Morin, Marie-Ève; Lacasse, Patrick; Lavigne, Pierre; Escher, Emanuel; Leduc, Richard; Guillemette, Gaétan

    2009-01-01

    The octapeptide hormone angiotensin II exerts a wide variety of cardiovascular effects through the activation of the angiotensin II Type 1 (AT1) receptor, which belongs to the G protein-coupled receptor superfamily. Like other G protein- coupled receptors, the AT1 receptor possesses seven transmembrane domains that provide structural support for the formation of the ligand-binding pocket. The role of the fifth transmembrane domain (TMD5) was investigated using the substituted cysteine accessibility method. All of the residues within Thr-190 to Leu-217 region were mutated one at a time to cysteine, and after expression in COS-7 cells, the mutant receptors were treated with the sulfhydryl-specific alkylating agent methanethiosulfonate-ethylammonium (MTSEA). MTSEA reacts selectively with water-accessible, free sulfhydryl groups of endogenous or introduced point mutation cysteines. If a cysteine is found in the binding pocket, the covalent modification will affect the binding kinetics of the ligand. MTSEA substantially decreased the binding affinity of L197C-AT1, N200C-AT1, I201C-AT1, G203C-AT1, and F204C-AT1 mutant receptors, which suggests that these residues orient themselves within the water-accessible binding pocket of the AT1 receptor. Interestingly, this pattern of acquired MTSEA sensitivity was altered for TMD5 reporter cysteines engineered in a constitutively active N111G-AT1 receptor background. Indeed, mutant I201C-N111G-AT1 became more sensitive to MTSEA, whereas mutant G203C-N111G-AT1 lost some sensitivity. Our results suggest that constitutive activation of AT1 receptor causes an apparent counterclockwise rotation of TMD5 as viewed from the extracellular side. PMID:19773549

  15. The fifth transmembrane domain of angiotensin II Type 1 receptor participates in the formation of the ligand-binding pocket and undergoes a counterclockwise rotation upon receptor activation.

    Science.gov (United States)

    Domazet, Ivana; Martin, Stéphane S; Holleran, Brian J; Morin, Marie-Eve; Lacasse, Patrick; Lavigne, Pierre; Escher, Emanuel; Leduc, Richard; Guillemette, Gaétan

    2009-11-13

    The octapeptide hormone angiotensin II exerts a wide variety of cardiovascular effects through the activation of the angiotensin II Type 1 (AT(1)) receptor, which belongs to the G protein-coupled receptor superfamily. Like other G protein- coupled receptors, the AT(1) receptor possesses seven transmembrane domains that provide structural support for the formation of the ligand-binding pocket. The role of the fifth transmembrane domain (TMD5) was investigated using the substituted cysteine accessibility method. All of the residues within Thr-190 to Leu-217 region were mutated one at a time to cysteine, and after expression in COS-7 cells, the mutant receptors were treated with the sulfhydryl-specific alkylating agent methanethiosulfonate-ethylammonium (MTSEA). MTSEA reacts selectively with water-accessible, free sulfhydryl groups of endogenous or introduced point mutation cysteines. If a cysteine is found in the binding pocket, the covalent modification will affect the binding kinetics of the ligand. MTSEA substantially decreased the binding affinity of L197C-AT(1), N200C-AT(1), I201C-AT(1), G203C-AT(1), and F204C-AT(1) mutant receptors, which suggests that these residues orient themselves within the water-accessible binding pocket of the AT(1) receptor. Interestingly, this pattern of acquired MTSEA sensitivity was altered for TMD5 reporter cysteines engineered in a constitutively active N111G-AT(1) receptor background. Indeed, mutant I201C-N111G-AT(1) became more sensitive to MTSEA, whereas mutant G203C-N111G-AT(1) lost some sensitivity. Our results suggest that constitutive activation of AT(1) receptor causes an apparent counterclockwise rotation of TMD5 as viewed from the extracellular side.

  16. International Union of Pharmacology. LXXXIX. Update on the Extended Family of Chemokine Receptors and Introducing a New Nomenclature for Atypical Chemokine Receptors

    Science.gov (United States)

    Bachelerie, Francoise; Ben-Baruch, Adit; Burkhardt, Amanda M.; Combadiere, Christophe; Farber, Joshua M.; Graham, Gerard J.; Horuk, Richard; Sparre-Ulrich, Alexander Hovard; Locati, Massimo; Luster, Andrew D.; Mantovani, Alberto; Matsushima, Kouji; Nibbs, Robert; Nomiyama, Hisayuki; Power, Christine A.; Proudfoot, Amanda E. I.; Rosenkilde, Mette M.; Rot, Antal; Sozzani, Silvano; Thelen, Marcus; Yoshie, Osamu; Zlotnik, Albert

    2014-01-01

    Sixteen years ago, the Nomenclature Committee of the International Union of Pharmacology approved a system for naming human seven-transmembrane (7TM) G protein-coupled chemokine receptors, the large family of leukocyte chemoattractant receptors that regulates immune system development and function, in large part by mediating leukocyte trafficking. This was announced in Pharmacological Reviews in a major overview of the first decade of research in this field [Murphy PM, Baggiolini M, Charo IF, Hébert CA, Horuk R, Matsushima K, Miller LH, Oppenheim JJ, and Power CA (2000) Pharmacol Rev 52:145–176]. Since then, several new receptors have been discovered, and major advances have been made for the others in many areas, including structural biology, signal transduction mechanisms, biology, and pharmacology. New and diverse roles have been identified in infection, immunity, inflammation, development, cancer, and other areas. The first two drugs acting at chemokine receptors have been approved by the U.S. Food and Drug Administration (FDA), maraviroc targeting CCR5 in human immunodeficiency virus (HIV)/AIDS, and plerixafor targeting CXCR4 for stem cell mobilization for transplantation in cancer, and other candidates are now undergoing pivotal clinical trials for diverse disease indications. In addition, a subfamily of atypical chemokine receptors has emerged that may signal through arrestins instead of G proteins to act as chemokine scavengers, and many microbial and invertebrate G protein-coupled chemokine receptors and soluble chemokine-binding proteins have been described. Here, we review this extended family of chemokine receptors and chemokine-binding proteins at the basic, translational, and clinical levels, including an update on drug development. We also introduce a new nomenclature for atypical chemokine receptors with the stem ACKR (atypical chemokine receptor) approved by the Nomenclature Committee of the International Union of Pharmacology and the Human

  17. Dopamine D2L receptor-interacting proteins regulate dopaminergic signaling

    Directory of Open Access Journals (Sweden)

    Norifumi Shioda

    2017-10-01

    Full Text Available Dopamine receptor family proteins include seven transmembrane and trimeric GTP-binding protein-coupled receptors (GPCRs. Among them, the dopamine D2 receptor (D2R is most extensively studied. All clinically used antipsychotic drugs serve as D2R antagonists in the mesolimbic dopamine system, and their ability to block D2R signaling is positively correlated with antipsychotic efficiency. Human genetic studies also show a significant association of DRD2 polymorphisms with disorders including schizophrenia and Parkinson's disease. D2R exists as two alternatively spliced isoforms, the long isoform (D2LR and the short isoform (D2SR, which differ in a 29-amino acid (AA insert in the third cytoplasmic loop. Importantly, previous reports demonstrate functional diversity between the two isoforms in humans. In this review, we focus on binding proteins that specifically interact with the D2LR 29AA insert. We discuss how D2R activities are mediated not only by heterotrimeric G proteins but by D2LR-interacting proteins, which in part regulate diverse D2R activities. Keywords: Dopamine D2L receptor, Antipsychotic drugs, DRD2 polymorphisms, Alternatively spliced isoforms, D2LR-interacting proteins

  18. Pathophysiology of GPCR Homo- and Heterodimerization: Special Emphasis on Somatostatin Receptors

    Directory of Open Access Journals (Sweden)

    Rishi K. Somvanshi

    2012-04-01

    Full Text Available G-protein coupled receptors (GPCRs are cell surface proteins responsible for translating >80% of extracellular reception to intracellular signals. The extracellular information in the form of neurotransmitters, peptides, ions, odorants etc is converted to intracellular signals via a wide variety of effector molecules activating distinct downstream signaling pathways. All GPCRs share common structural features including an extracellular N-terminal, seven-transmembrane domains (TMs linked by extracellular/intracellular loops and the C-terminal tail. Recent studies have shown that most GPCRs function as dimers (homo- and/or heterodimers or even higher order of oligomers. Protein-protein interaction among GPCRs and other receptor proteins play a critical role in the modulation of receptor pharmacology and functions. Although ~50% of the current drugs available in the market target GPCRs, still many GPCRs remain unexplored as potential therapeutic targets, opening immense possibility to discover the role of GPCRs in pathophysiological conditions. This review explores the existing information and future possibilities of GPCRs as tools in clinical pharmacology and is specifically focused for the role of somatostatin receptors (SSTRs in pathophysiology of diseases and as the potential candidate for drug discovery.

  19. The emerging role of promiscuous 7TM receptors as chemosensors for food intake.

    Science.gov (United States)

    Wellendorph, Petrine; Johansen, Lars Dan; Bräuner-Osborne, Hans

    2010-01-01

    In recent years, several highly promiscuous seven transmembrane (7TM) receptors have been cloned and characterized of which many are activated broadly by amino acids, proteolytic degradation products, carbohydrates, or free fatty acids (FFAs) and are expressed in taste tissue, the gastrointestinal (GI) tract, endocrine glands, adipose tissue, and/or kidney. This has led to the hypothesis that these receptors may act as sensors of food intake modulating, for example, release of incretin hormones from the gut, insulin/glucagon from the pancreas, and leptin from adipose tissue. In the present review, we describe the molecular mechanisms of nutrient-sensing of the calcium-sensing receptor (CaR), the G protein-coupled receptor family C, group 6, subtype A (GPRC6A), and the taste1 receptor T1R1/T1R3-sensing L-α-amino acids; the carbohydrate-sensing T1R2/T1R3 receptor; the proteolytic degradation product sensor GPR93 (also termed GPR92); and the FFA sensing receptors FFA1, FFA2, FFA3, GPR84, and GPR120. Due to their omnipresent nature, the natural ligands have had limited usability in pharmacological/physiological studies which has hampered the elucidation of the physiological function and therapeutic prospect of their receptors. However, an increasing number of subtype-selective ligands and/or receptor knockout mice are being developed which at least for some of the receptors have validated them as promising drug targets in, for example, type II diabetes. Copyright © 2010 Elsevier Inc. All rights reserved.

  20. Combination of biased forecasts: Bias correction or bias based weights?

    OpenAIRE

    Wenzel, Thomas

    1999-01-01

    Most of the literature on combination of forecasts deals with the assumption of unbiased individual forecasts. Here, we consider the case of biased forecasts and discuss two different combination techniques resulting in an unbiased forecast. On the one hand we correct the individual forecasts, and on the other we calculate bias based weights. A simulation study gives some insight in the situations where we should use the different methods.

  1. Differential Requirement of the Extracellular Domain in Activation of Class B G Protein-coupled Receptors.

    Science.gov (United States)

    Zhao, Li-Hua; Yin, Yanting; Yang, Dehua; Liu, Bo; Hou, Li; Wang, Xiaoxi; Pal, Kuntal; Jiang, Yi; Feng, Yang; Cai, Xiaoqing; Dai, Antao; Liu, Mingyao; Wang, Ming-Wei; Melcher, Karsten; Xu, H Eric

    2016-07-15

    G protein-coupled receptors (GPCRs) from the secretin-like (class B) family are key players in hormonal homeostasis and are important drug targets for the treatment of metabolic disorders and neuronal diseases. They consist of a large N-terminal extracellular domain (ECD) and a transmembrane domain (TMD) with the GPCR signature of seven transmembrane helices. Class B GPCRs are activated by peptide hormones with their C termini bound to the receptor ECD and their N termini bound to the TMD. It is thought that the ECD functions as an affinity trap to bind and localize the hormone to the receptor. This in turn would allow the hormone N terminus to insert into the TMD and induce conformational changes of the TMD to activate downstream signaling. In contrast to this prevailing model, we demonstrate that human class B GPCRs vary widely in their requirement of the ECD for activation. In one group, represented by corticotrophin-releasing factor receptor 1 (CRF1R), parathyroid hormone receptor (PTH1R), and pituitary adenylate cyclase activating polypeptide type 1 receptor (PAC1R), the ECD requirement for high affinity hormone binding can be bypassed by induced proximity and mass action effects, whereas in the other group, represented by glucagon receptor (GCGR) and glucagon-like peptide-1 receptor (GLP-1R), the ECD is required for signaling even when the hormone is covalently linked to the TMD. Furthermore, the activation of GLP-1R by small molecules that interact with the intracellular side of the receptor is dependent on the presence of its ECD, suggesting a direct role of the ECD in GLP-1R activation. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  2. Benefits of being biased!

    Indian Academy of Sciences (India)

    Administrator

    Journal of Genetics, Vol. 83, No. 2, August 2004. Keywords. codon bias; alcohol dehydrogenase; Darwinian ... RESEARCH COMMENTARY. Benefits of being biased! SUTIRTH DEY*. Evolutionary Biology Laboratory, Evolutionary & Organismal Biology Unit,. Jawaharlal Nehru Centre for Advanced Scientific Research,.

  3. Ligand-specific regulation of the extracellular surface of a G-protein-coupled receptor

    Energy Technology Data Exchange (ETDEWEB)

    Bokoch, Michael P.; Zou, Yaozhong; Rasmussen, Søren G.F.; Liu, Corey W.; Nygaard, Rie; Rosenbaum, Daniel M.; Fung, Juan José; Choi, Hee-Jung; Thian, Foon Sun; Kobilka, Tong Sun; Puglisi, Joseph D.; Weis, William I.; Pardo, Leonardo; Prosser, R. Scott; Mueller, Luciano; Kobilka, Brian K. (Stanford-MED); (Toronto); (BMS); (UAB, Spain)

    2010-01-14

    G-protein-coupled receptors (GPCRs) are seven-transmembrane proteins that mediate most cellular responses to hormones and neurotransmitters. They are the largest group of therapeutic targets for a broad spectrum of diseases. Recent crystal structures of GPCRs have revealed structural conservation extending from the orthosteric ligand-binding site in the transmembrane core to the cytoplasmic G-protein-coupling domains. In contrast, the extracellular surface (ECS) of GPCRs is remarkably diverse and is therefore an ideal target for the discovery of subtype-selective drugs. However, little is known about the functional role of the ECS in receptor activation, or about conformational coupling of this surface to the native ligand-binding pocket. Here we use NMR spectroscopy to investigate ligand-specific conformational changes around a central structural feature in the ECS of the {beta}{sub 2} adrenergic receptor: a salt bridge linking extracellular loops 2 and 3. Small-molecule drugs that bind within the transmembrane core and exhibit different efficacies towards G-protein activation (agonist, neutral antagonist and inverse agonist) also stabilize distinct conformations of the ECS. We thereby demonstrate conformational coupling between the ECS and the orthosteric binding site, showing that drugs targeting this diverse surface could function as allosteric modulators with high subtype selectivity. Moreover, these studies provide a new insight into the dynamic behaviour of GPCRs not addressable by static, inactive-state crystal structures.

  4. Functional enhancement of AT1R potency in the presence of the TPαR is revealed by a comprehensive 7TM receptor co-expression screen.

    Directory of Open Access Journals (Sweden)

    Jonas Tind Hansen

    Full Text Available BACKGROUND: Functional cross-talk between seven transmembrane (7TM receptors can dramatically alter their pharmacological properties, both in vitro and in vivo. This represents an opportunity for the development of novel therapeutics that potentially target more specific biological effects while causing fewer adverse events. Although several studies convincingly have established the existence of 7TM receptor cross-talk, little is known about the frequencey and biological significance of this phenomenon. METHODOLOGY/PRINCIPAL FINDINGS: To evaluate the extent of synergism in 7TM receptor signaling, we took a comprehensive approach and co-expressed 123 different 7TM receptors together with the angiotensin II type 1 receptor (AT1R and analyzed how each receptor affected the angiotensin II (AngII response. To monitor the effect we used integrative receptor activation/signaling assay called Receptor Selection and Amplification Technology (R-SAT. In this screen the thromboxane A2α receptor (TPαR was the only receptor which significantly enhanced the AngII-mediated response. The TPαR-mediated enhancement of AngII signaling was significantly reduced when a signaling deficient receptor mutant (TPαR R130V was co-expressed instead of the wild-type TPαR, and was completely blocked both by TPαR antagonists and COX inhibitors inhibiting formation of thromboxane A2 (TXA2. CONCLUSIONS/SIGNIFICANCE: We found a functional enhancement of AT1R only when co-expressed with TPαR, but not with 122 other 7TM receptors. In addition, the TPαR must be functionally active, indicating the AT1R enhancement is mediated by a paracrine mechanism. Since we only found one receptor enhancing AT1R potency, our results suggest that functional augmentation through 7TM receptor cross-talk is a rare event that may require specific conditions to occur.

  5. Cholesterol depletion induces dynamic confinement of the G-protein coupled serotonin(1A) receptor in the plasma membrane of living cells.

    Science.gov (United States)

    Pucadyil, Thomas J; Chattopadhyay, Amitabha

    2007-03-01

    Cholesterol is an essential constituent of eukaryotic membranes and plays a crucial role in membrane organization, dynamics, function, and sorting. It is often found distributed non-randomly in domains or pools in biological and model membranes and is thought to contribute to a segregated distribution of membrane constituents. Signal transduction events mediated by seven transmembrane domain G-protein coupled receptors (GPCRs) are the primary means by which cells communicate with and respond to their external environment. We analyzed the role of cholesterol in the plasma membrane organization of the G-protein coupled serotonin(1A) receptor by fluorescence recovery after photobleaching (FRAP) measurements with varying bleach spot sizes. Our results show that lateral diffusion parameters of serotonin(1A) receptors in normal cells are consistent with models describing diffusion of molecules in a homogenous membrane. Interestingly, these characteristics are altered in cholesterol-depleted cells in a manner that is consistent with dynamic confinement of serotonin(1A) receptors in the plasma membrane. Importantly, analysis of ligand binding and downstream signaling of the serotonin(1A) receptor suggests that receptor function is affected in a significantly different manner when intact cells or isolated membranes are depleted of cholesterol. These results assume significance in the context of interpreting effects of cholesterol depletion on diffusion characteristics of membrane proteins in particular, and cholesterol-dependent cellular processes in general.

  6. Gene : CBRC-DNOV-01-2512 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available _HUMAN 2e-39 39% ref|XP_001364675.1| PREDICTED: similar to seven transmembrane helix receptor [Monodelphis d...LTVVSYVYIISTILKIPSGQD*RKASATCASHFTVVSMGYGISIFVYVCPSQKSSLHLSKILFIPSQCHHTSPKSLHLLSME ...

  7. Gene : CBRC-GGOR-01-1244 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available 97% ref|XP_521992.2| PREDICTED: similar to seven transmembrane helix receptor [Pan troglodytes] 3e-70 98% MV...ECFLLAVMAYDRYVAIRNPLLYTVAERNGTERNGTERNSMEWNGMEWNSMEWNGIQWNGMEWNGTVRNGTERNGMEFHGMEWNGMEFHGMEFNAMQRXXXXXXALLAQARTIELEIFLIT ...

  8. Gene : CBRC-OPRI-01-0327 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available 4e-59 85% ref|XP_521803.2| PREDICTED: similar to seven transmembrane helix receptor [Pan troglodytes] 2e-60 ...87% MMSLSNSSWRLPQPTFFLVGIPGLEESQHWIALLLAVLYFLALSGNVTILFIVWVDSSLHQPMYLFLAMLAAIDLVLASSTAPKALAVLLIHAHEIGYICCLVQMFFIHAFSSMESGVLVAMALDRYVAYCTLCTTXXXXXXXX ...

  9. Gene : CBRC-MMUR-01-1612 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available 1e-56 41% ref|XP_001497978.2| PREDICTED: similar to seven transmembrane helix receptor [Equus caballus] 5e-6...IPPVLRLACADTTEVEAIVFSSSALLILFTVMVILLSYAYILVTICSMRSLEAQGKALSTCASHLTIICLFYGTITFMYAQPSSHNSMEQNKVVSVVYTVVIPMLNPLIYSLRNKDVKHALKRRCQGKLPS ...

  10. Two Seven-Transmembrane Domain MILDEW RESISTANCE LOCUS O Proteins Cofunction in Arabidopsis Root Thigmomorphogenesis[C][W

    Science.gov (United States)

    Chen, Zhongying; Noir, Sandra; Kwaaitaal, Mark; Hartmann, H. Andreas; Wu, Ming-Jing; Mudgil, Yashwanti; Sukumar, Poornima; Muday, Gloria; Panstruga, Ralph; Jones, Alan M.

    2009-01-01

    Directional root expansion is governed by nutrient gradients, positive gravitropism and hydrotropism, negative phototropism and thigmotropism, as well as endogenous oscillations in the growth trajectory (circumnutation). Null mutations in phylogenetically related Arabidopsis thaliana genes MILDEW RESISTANCE LOCUS O 4 (MLO4) and MLO11, encoding heptahelical, plasma membrane–localized proteins predominantly expressed in the root tip, result in aberrant root thigmomorphogenesis. mlo4 and mlo11 mutant plants show anisotropic, chiral root expansion manifesting as tightly curled root patterns upon contact with solid surfaces. The defect in mlo4 and mlo11 mutants is nonadditive and dependent on light and nutrients. Genetic epistasis experiments demonstrate that the mutant phenotype is independently modulated by the Gβ subunit of the heterotrimeric G-protein complex. Analysis of expressed chimeric MLO4/MLO2 proteins revealed that the C-terminal domain of MLO4 is necessary but not sufficient for MLO4 action in root thigmomorphogenesis. The expression of the auxin efflux carrier fusion, PIN1-green fluorescent protein, the pattern of auxin-induced gene expression, and acropetal as well as basipetal auxin transport are altered at the root tip of mlo4 mutant seedlings. Moreover, addition of auxin transport inhibitors or the loss of EIR1/AGR1/PIN2 function abolishes root curling of mlo4, mlo11, and wild-type seedlings. These results demonstrate that the exaggerated root curling phenotypes of the mlo4 and mlo11 mutants depend on auxin gradients and suggest that MLO4 and MLO11 cofunction as modulators of touch-induced root tropism. PMID:19602625

  11. CPI Bias in Korea

    Directory of Open Access Journals (Sweden)

    Chul Chung

    2007-12-01

    Full Text Available We estimate the CPI bias in Korea by employing the approach of Engel’s Law as suggested by Hamilton (2001. This paper is the first attempt to estimate the bias using Korean panel data, Korean Labor and Income Panel Study(KLIPS. Following Hamilton’s model with non­linear specification correction, our estimation result shows that the cumulative CPI bias over the sample period (2000-2005 was 0.7 percent annually. This CPI bias implies that about 21 percent of the inflation rate during the period can be attributed to the bias. In light of purchasing power parity, we provide an interpretation of the estimated bias.

  12. Olfactory receptor signaling is regulated by the post-synaptic density 95, Drosophila discs large, zona-occludens 1 (PDZ) scaffold multi-PDZ domain protein 1.

    LENUS (Irish Health Repository)

    Dooley, Ruth

    2009-12-01

    The unique ability of mammals to detect and discriminate between thousands of different odorant molecules is governed by the diverse array of olfactory receptors expressed by olfactory sensory neurons in the nasal epithelium. Olfactory receptors consist of seven transmembrane domain G protein-coupled receptors and comprise the largest gene superfamily in the mammalian genome. We found that approximately 30% of olfactory receptors possess a classical post-synaptic density 95, Drosophila discs large, zona-occludens 1 (PDZ) domain binding motif in their C-termini. PDZ domains have been established as sites for protein-protein interaction and play a central role in organizing diverse cell signaling assemblies. In the present study, we show that multi-PDZ domain protein 1 (MUPP1) is expressed in the apical compartment of olfactory sensory neurons. Furthermore, on heterologous co-expression with olfactory sensory neurons, MUPP1 was shown to translocate to the plasma membrane. We found direct interaction of PDZ domains 1 + 2 of MUPP1 with the C-terminus of olfactory receptors in vitro. Moreover, the odorant-elicited calcium response of OR2AG1 showed a prolonged decay in MUPP1 small interfering RNA-treated cells. We have therefore elucidated the first building blocks of the putative \\'olfactosome\\

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

    Science.gov (United States)

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

    2011-01-01

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

  14. G protein-coupled receptor 84, a microglia-associated protein expressed in neuroinflammatory conditions.

    Science.gov (United States)

    Bouchard, Caroline; Pagé, Julie; Bédard, Andréanne; Tremblay, Pierrot; Vallières, Luc

    2007-06-01

    G protein-coupled receptor 84 (GPR84) is a recently discovered member of the seven transmembrane receptor superfamily whose function and regulation are unknown. Here, we report that in mice suffering from endotoxemia, microglia express GPR84 in a strong and sustained manner. This property is shared by subpopulations of peripheral macrophages and, to a much lesser extent, monocytes. The induction of GPR84 expression by endotoxin is mediated, at least in part, by proinflammatory cytokines, notably tumor necrosis factor (TNF) and interleukin-1 (IL-1), because mice lacking either one or both of these molecules have fewer GPR84-expressing cells in their cerebral cortex than wild-type mice during the early phase of endotoxemia. Moreover, when injected intracerebrally or added to microglial cultures, recombinant TNF stimulates GPR84 expression through a dexamethasone-insensitive mechanism. Finally, we show that microglia produce GPR84 not only during endotoxemia, but also during experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis. In conclusion, this study reports the identification of a new sensitive marker of microglial activation, which may play an important regulatory role in neuroimmunological processes, acting downstream to the effects of proinflammatory mediators.

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

    Science.gov (United States)

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

    2018-02-14

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

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

    Directory of Open Access Journals (Sweden)

    Gamariel Rwibasira Rudinga

    2018-02-01

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

  17. Sampler bias -- Phase 1

    International Nuclear Information System (INIS)

    Blanchard, R.J.

    1995-01-01

    This documents Phase 1 determinations on sampler induced bias for four sampler types used in tank characterization. Each sampler, grab sampler or bottle-on-a-string, auger sampler, sludge sampler and universal sampler, is briefly discussed and their physical limits noted. Phase 2 of this document will define additional testing and analysis to further define Sampler Bias

  18. Photovoltaic Bias Generator

    Science.gov (United States)

    2018-02-01

    Department of the Army position unless so designated by other authorized documents. Citation of manufacturer’s or trade names does not constitute an... Interior view of the photovoltaic bias generator showing wrapped-wire side of circuit board...3 Fig. 4 Interior view of the photovoltaic bias generator showing component side of circuit board

  19. Biases in categorization

    NARCIS (Netherlands)

    Das-Smaal, E.A.

    1990-01-01

    On what grounds can we conclude that an act of categorization is biased? In this chapter, it is contended that in the absence of objective norms of what categories actually are, biases in categorization can only be specified in relation to theoretical understandings of categorization. Therefore, the

  20. Molecular characterization and expression profile of the melatonin receptor MT1 in the ovary of Tianzhu white yak (Bos grunniens).

    Science.gov (United States)

    Hu, Jun Jie; Zhang, Xiao Yu; Zhang, Yong; Zhao, Xing Xu; Li, Fa Di; Tao, Jin Zhong

    2017-02-01

    Melatonin plays crucial roles in a wide range of ovarian physiological functions via the melatonin receptors (MRs). Structure and function of MRs have been well studied in sheep, cattle, and humans, but little information exists on the genetic characterization and function of these receptors in the ovary of the white yak. In the present study, the melatonin receptor MT1 was cloned by RT-PCR in the ovary of white yak; the MT1 cDNA fragment obtained (843bp) comprised an open reading frame (827bp) encoding a protein containing 275 residues, characterized by seven transmembrane regions and an NRY motif, two distinct amino acid replacements were found. The white yak MT1 had a 83.9-98.6% protein sequence identity with that of nine other mammals. Using RT-PCR, the expression levels of MT1, MT2, and LHR in the ovary of pregnant and non-pregnant white yaks were compared, revealing higher levels of all genes in pregnant yaks: 3.83-fold increase for MT1 (Pmelatonin and MT1 are associated with the corpus luteum function of pregnancy maintenance and follicular development during oocyte maturation in the white yak. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Approximate Bias Correction in Econometrics

    OpenAIRE

    James G. MacKinnon; Anthony A. Smith Jr.

    1995-01-01

    This paper discusses ways to reduce the bias of consistent estimators that are biased in finite samples. It is necessary that the bias function, which relates parameter values to bias, should be estimable by computer simulation or by some other method. If so, bias can be reduced or, in some cases that may not be unrealistic, even eliminated. In general, several evaluations of the bias function will be required to do this. Unfortunately, reducing bias may increase the variance, or even the mea...

  2. NK1 receptor fused to beta-arrestin displays a single-component, high-affinity molecular phenotype.

    Science.gov (United States)

    Martini, Lene; Hastrup, Hanne; Holst, Birgitte; Fraile-Ramos, Alberto; Marsh, Mark; Schwartz, Thue W

    2002-07-01

    Arrestins are cytosolic proteins that, upon stimulation of seven transmembrane (7TM) receptors, terminate signaling by binding to the receptor, displacing the G protein and targeting the receptor to clathrin-coated pits. Fusion of beta-arrestin1 to the C-terminal end of the neurokinin NK1 receptor resulted in a chimeric protein that was expressed to some extent on the cell surface but also accumulated in transferrin-labeled recycling endosomes independently of agonist stimulation. As expected, the fusion protein was almost totally silenced with respect to agonist-induced signaling through the normal Gq/G11 and Gs pathways. The NK1-beta-arrestin1 fusion construct bound nonpeptide antagonists with increased affinity but surprisingly also bound two types of agonists, substance P and neurokinin A, with high, normal affinity. In the wild-type NK1 receptor, neurokinin A (NKA) competes for binding against substance P and especially against antagonists with up to 1000-fold lower apparent affinity than determined in functional assays and in homologous binding assays. When the NK1 receptor was closely fused to G proteins, this phenomenon was eliminated among agonists, but the agonists still competed with low affinity against antagonists. In contrast, in the NK1-beta-arrestin1 fusion protein, all ligands bound with similar affinity independent of the choice of radioligand and with Hill coefficients near unity. We conclude that the NK1 receptor in complex with arrestin is in a high-affinity, stable, agonist-binding form probably best suited to structural analysis and that the receptor can display binding properties that are nearly theoretically ideal when it is forced to complex with only a single intracellular protein partner.

  3. RNA interference of pheromone biosynthesis-activating neuropeptide receptor suppresses mating behavior by inhibiting sex pheromone production in Plutella xylostella (L.).

    Science.gov (United States)

    Lee, Dae-Weon; Shrestha, Sony; Kim, A Young; Park, Seok Joo; Yang, Chang Yeol; Kim, Yonggyun; Koh, Young Ho

    2011-04-01

    Sex pheromone production is regulated by pheromone biosynthesis-activating neuropeptide (PBAN) in many lepidopteran species. We cloned a PBAN receptor (Plx-PBANr) gene from the female pheromone gland of the diamondback moth, Plutella xylostella (L.). Plx-PBANr encodes 338 amino acids and has conserved structural motifs implicating in promoting G protein coupling and tyrosine-based sorting signaling along with seven transmembrane domains, indicating a typical G protein-coupled receptor. The expression of Plx-PBANr was found only in the pheromone gland of female adults among examined tissues and developmental stages. Heterologous expression in human uterus cervical cancer cells revealed that Plx-PBANr induced significant calcium elevation when challenged with Plx-PBAN. Female P. xylostella injected with double-stranded RNA specific to Plx-PBANr showed suppression of the receptor gene expression and exhibited significant reduction in pheromone biosynthesis, which resulted in loss of male attractiveness. Taken together, the identified PBAN receptor is functional in PBAN signaling via calcium secondary messenger, which leads to activation of pheromone biosynthesis and male attraction. Copyright © 2011 Elsevier Ltd. All rights reserved.

  4. Bias aware Kalman filters

    DEFF Research Database (Denmark)

    Drecourt, J.-P.; Madsen, H.; Rosbjerg, Dan

    2006-01-01

    This paper reviews two different approaches that have been proposed to tackle the problems of model bias with the Kalman filter: the use of a colored noise model and the implementation of a separate bias filter. Both filters are implemented with and without feedback of the bias into the model state....... The colored noise filter formulation is extended to correct both time correlated and uncorrelated model error components. A more stable version of the separate filter without feedback is presented. The filters are implemented in an ensemble framework using Latin hypercube sampling. The techniques...... are illustrated on a simple one-dimensional groundwater problem. The results show that the presented filters outperform the standard Kalman filter and that the implementations with bias feedback work in more general conditions than the implementations without feedback. 2005 Elsevier Ltd. All rights reserved....

  5. Biases in casino betting

    Directory of Open Access Journals (Sweden)

    James Sundali

    2006-07-01

    Full Text Available We examine two departures of individual perceptions of randomness from probability theory: the hot hand and the gambler's fallacy, and their respective opposites. This paper's first contribution is to use data from the field (individuals playing roulette in a casino to demonstrate the existence and impact of these biases that have been previously documented in the lab. Decisions in the field are consistent with biased beliefs, although we observe significant individual heterogeneity in the population. A second contribution is to separately identify these biases within a given individual, then to examine their within-person correlation. We find a positive and significant correlation across individuals between hot hand and gambler's fallacy biases, suggesting a common (root cause of the two related errors. We speculate as to the source of this correlation (locus of control, and suggest future research which could test this speculation.

  6. Introduction to Unconscious Bias

    Science.gov (United States)

    Schmelz, Joan T.

    2010-05-01

    We all have biases, and we are (for the most part) unaware of them. In general, men and women BOTH unconsciously devalue the contributions of women. This can have a detrimental effect on grant proposals, job applications, and performance reviews. Sociology is way ahead of astronomy in these studies. When evaluating identical application packages, male and female University psychology professors preferred 2:1 to hire "Brian” over "Karen” as an assistant professor. When evaluating a more experienced record (at the point of promotion to tenure), reservations were expressed four times more often when the name was female. This unconscious bias has a repeated negative effect on Karen's career. This talk will introduce the concept of unconscious bias and also give recommendations on how to address it using an example for a faculty search committee. The process of eliminating unconscious bias begins with awareness, then moves to policy and practice, and ends with accountability.

  7. Australia's Bond Home Bias

    OpenAIRE

    Anil V. Mishra; Umaru B. Conteh

    2014-01-01

    This paper constructs the float adjusted measure of home bias and explores the determinants of bond home bias by employing the International Monetary Fund's high quality dataset (2001 to 2009) on cross-border bond investment. The paper finds that Australian investors' prefer investing in countries with higher economic development and more developed bond markets. Exchange rate volatility appears to be an impediment for cross-border bond investment. Investors prefer investing in countries with ...

  8. The Mouse Solitary Odorant Receptor Gene Promoters as Models for the Study of Odorant Receptor Gene Choice.

    Directory of Open Access Journals (Sweden)

    Andrea Degl'Innocenti

    Full Text Available In vertebrates, several anatomical regions located within the nasal cavity mediate olfaction. Among these, the main olfactory epithelium detects most conventional odorants. Olfactory sensory neurons, provided with cilia exposed to the air, detect volatile chemicals via an extremely large family of seven-transmembrane chemoreceptors named odorant receptors. Their genes are expressed in a monogenic and monoallelic fashion: a single allele of a single odorant receptor gene is transcribed in a given mature neuron, through a still uncharacterized molecular mechanism known as odorant receptor gene choice.Odorant receptor genes are typically arranged in genomic clusters, but a few are isolated (we call them solitary from the others within a region broader than 1 Mb upstream and downstream with respect to their transcript's coordinates. The study of clustered genes is problematic, because of redundancy and ambiguities in their regulatory elements: we propose to use the solitary genes as simplified models to understand odorant receptor gene choice.Here we define number and identity of the solitary genes in the mouse genome (C57BL/6J, and assess the conservation of the solitary status in some mammalian orthologs. Furthermore, we locate their putative promoters, predict their homeodomain binding sites (commonly present in the promoters of odorant receptor genes and compare candidate promoter sequences with those of wild-caught mice. We also provide expression data from histological sections.In the mouse genome there are eight intact solitary genes: Olfr19 (M12, Olfr49, Olfr266, Olfr267, Olfr370, Olfr371, Olfr466, Olfr1402; five are conserved as solitary in rat. These genes are all expressed in the main olfactory epithelium of three-day-old mice. The C57BL/6J candidate promoter of Olfr370 has considerably varied compared to its wild-type counterpart. Within the putative promoter for Olfr266 a homeodomain binding site is predicted. As a whole, our findings

  9. Cloning and functional characterization of the DA2 receptor gene in Chinese mitten crab (Eriocheir sinensis)

    Science.gov (United States)

    Xu, Min-jie; Zhang, Cong; Yang, Zhigang

    2018-01-01

    Dopamine (DA) plays a modulatory role in numerous physiological processes such as light adaptation and food intake, and exerts these functions through DA receptors (DARs). This study presents, for the first time, isolation and characterization of the dopamine receptor 2(DA2 receptor) cDNA from the intestinal tissue of Eriocheir sinensis, an economically important freshwater aquaculture species in China. The DA2 receptor cDNA sequence, which was obtained by rapid amplification of cDNA ends, is 2369bp long, encode peptide of 589 amino acid, and is highly homologous to related sequences in crustaceans. Analysis of the deduced amino acid sequence and the structure of the DA2 indicated that this receptor is a member of the family of G protein-coupled receptors (GPCRs), as it contains seven transmembrane domains and other common signatures of GPCRs. RT-PCR showed that the expression of the DA2 receptor gene was distributed in various tissues, and high expression levels were observed in the cranial ganglia and the thoracic ganglia. Further study of the effect of photoperiod on DA2 expression showed that constant darkness induced a significant increase in DA2 expression in the cranial ganglia. Finally, analysis of DA2 receptor expression under different feeding statuses showed that there was significantly greater expression in the hepatopancreas and intestines after feeding than before feeding, but there were no differences in expression between the before feeding and during feeding periods in either tissue. Our results indicate that the DA2 receptor structurally belongs to the family of G protein-coupled receptors, and that the cranial ganglia are the main tissues in which the DA2 receptor participates in light adaptation during dark hours. In addition, the DA2 receptor in E. sinensis may be involved in the physiological regulation of the hepatopancreas and digestive tract after the ingestion of food. This study provides a foundation for further exploration of the light

  10. Expression of the adhesion G protein-coupled receptor A2 (adgra2) during Xenopus laevis development.

    Science.gov (United States)

    Seigfried, Franziska A; Dietmann, Petra; Kühl, Michael; Kühl, Susanne J

    2018-06-01

    The adhesion G protein-coupled receptor A2 (Adgra2) is a seven transmembrane receptor that has been described to be a regulator for angiogenesis in mice. Furthermore, the zebrafish ouchless mutant is unable to develop dorsal root ganglia through a disrupted trafficking of Adgra2. Besides RNA sequencing data, nothing is reported about Adgra2 in the south African crawled frog Xenopus laevis. In this study, we investigated for the first time the spatio-temporal expression of adgra2 during early Xenopus embryogenesis in detail. In silico approaches showed that the genomic adgra2 region as well as the Adgra2 protein sequence is highly conserved among different species including Xenopus. RT-PCR experiments confirmed that embryonic adgra2 expression is primarily detected at the beginning of neurulation and is then present throughout the whole Xenopus embryogenesis until stage 42. Whole mount in situ hybridization approaches visualized adgra2 expression in many tissues during Xenopus embryogenesis such as the cardiovascular system including the heart, the migrating neural crest cells and the developing eye including the periocular mesenchyme. Our results indicate a role of Adgra2 for embryogenesis and are a good starting point for further functional studies during early vertebrate development. Copyright © 2018 Elsevier B.V. All rights reserved.

  11. Gene : CBRC-PABE-07-0025 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available e-82 48% ref|XP_001253185.1| PREDICTED: similar to seven transmembrane helix receptor [Bos taurus] ref|XP_00...1250982.1| PREDICTED: similar to seven transmembrane helix receptor [Bos taurus] 1e-130 78% MINDSYFSGFILLGFT...QIFIDVALYSVECILLAMMSCDRLNAICKPLHHMTIMNLQLCQGLVVISWVVGVINCIIPSPYAMSLPRSMEVTTFAMCLIIVLVPLLLILVSYGFIAVAVLKIKSAA

  12. Gene : CBRC-PTRO-07-0026 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available e-79 50% ref|XP_001253185.1| PREDICTED: similar to seven transmembrane helix receptor [Bos taurus] ref|XP_00...1250982.1| PREDICTED: similar to seven transmembrane helix receptor [Bos taurus] 1e-120 76% MINDSRFSGFILLGFT...QLFIDVALYSVECILLSMMSYDRLNAICKPLHHMTIMNLQLCQGLVVISWIVGVINCIIPSPYAMSLPRSMEVTTFAMCLIIVLVPLLLILVSYGFIAVAVLKIKSAAGRQKAFGTCSSHLIVVSIFYGTVRYMYTQPGNSPSQDEGKLLHIFYSIFTPTLNPSH ...

  13. Simulating publication bias

    DEFF Research Database (Denmark)

    Paldam, Martin

    is censoring: selection by the size of estimate; SR3 selects the optimal combination of fit and size; and SR4 selects the first satisficing result. The last four SRs are steered by priors and result in bias. The MST and the FAT-PET have been developed for detection and correction of such bias. The simulations......Economic research typically runs J regressions for each selected for publication – it is often selected as the ‘best’ of the regressions. The paper examines five possible meanings of the word ‘best’: SR0 is ideal selection with no bias; SR1 is polishing: selection by statistical fit; SR2...... are made by data variation, while the model is the same. It appears that SR0 generates narrow funnels much at odds with observed funnels, while the other four funnels look more realistic. SR1 to SR4 give the mean a substantial bias that confirms the prior causing the bias. The FAT-PET MRA works well...

  14. Measuring Agricultural Bias

    DEFF Research Database (Denmark)

    Jensen, Henning Tarp; Robinson, Sherman; Tarp, Finn

    The measurement issue is the key issue in the literature on trade policy-induced agri-cultural price incentive bias. This paper introduces a general equilibrium effective rate of protection (GE-ERP) measure, which extends and generalizes earlier partial equilibrium nominal protection measures...... shares and intersectoral linkages - are crucial for determining the sign and magnitude of trade policy bias. The GE-ERP measure is therefore uniquely suited to capture the full impact of trade policies on agricultural price incentives. A Monte Carlo procedure confirms that the results are robust....... For the 15 sample countries, the results indicate that the agricultural price incentive bias, which was generally perceived to exist during the 1980s, was largely eliminated during the 1990s. The results also demonstrate that general equilibrium effects and country-specific characteristics - including trade...

  15. Free fatty acids-sensing G protein-coupled receptors in drug targeting and therapeutics.

    Science.gov (United States)

    Yonezawa, Tomo; Kurata, Riho; Yoshida, Kaori; Murayama, Masanori A; Cui, Xiaofeng; Hasegawa, Akihiko

    2013-01-01

    G protein-coupled receptor (GPCR) (also known as seven-transmembrane domain receptor) superfamily represents the largest protein family in the human genome. These receptors respond to various physiological ligands such as photons, odors, pheromones, hormones, ions, and small molecules including amines, amino acids to large peptides and steroids. Thus, GPCRs are involved in many diseases and the target of around half of all conventional drugs. The physiological roles of free fatty acids (FFAs), in particular, long-chain FFAs, are important for the development of many metabolic disease including obesity, diabetes, and atherosclerosis. In the past half decade, deorphanization of several GPCRs has revealed that GPR40, GPR41, GPR43, GPR84 and GPR120 sense concentration of extracellular FFAs with various carbon chain lengths. GPR40 and GPR120 are activated by medium- and long-chain FFAs. GPR84 is activated by medium- chain, but not long-chain, FFAs. GPR41 and GPR43 are activated by short-chain FFAs. GPR40 is highly expressed in pancreatic beta cells and plays a crucial role in FFAs-induced insulin secretion. GPR120 is mainly expressed in enteroendocrine cells and plays an important role for FFAs-induced glucagon-like peptide-1. GPR43 is abundant in leukocytes and adipose tissue, whilst GPR41 is highly expressed in adipose tissue, the pancreas and leukocytes. GPR84 is expressed in leukocytes and monocyte/macrophage. This review aims to shed light on the physiological roles and development of drugs targeting these receptors.

  16. Adiponectin receptors form homomers and heteromers exhibiting distinct ligand binding and intracellular signaling properties.

    Science.gov (United States)

    Almabouada, Farid; Diaz-Ruiz, Alberto; Rabanal-Ruiz, Yoana; Peinado, Juan R; Vazquez-Martinez, Rafael; Malagon, Maria M

    2013-02-01

    Adiponectin binds to two widely expressed receptors (AdipoR1 and AdipoR2) that contain seven transmembrane domains but, unlike G-protein coupled receptors, present an extracellular C terminus and a cytosolic N terminus. Recently, AdipoR1 was found to associate in high order complexes. However, it is still unknown whether AdipoR2 may also form homomers or heteromers with AdipoR1 or if such interactions may be functionally relevant. Herein, we have analyzed the oligomerization pattern of AdipoRs by FRET and immunoprecipitation and evaluated both the internalization of AdipoRs in response to various adiponectin isoforms and the effect of adiponectin binding to different AdipoR combinations on AMP-activated protein kinase phosphorylation and peroxisome proliferator-activated receptor α activation. Transfection of HEK293AD cells with AdipoR1 and AdipoR2 showed that both receptors colocalize at both the plasma membrane and the endoplasmic reticulum. Co-transfection with the different AdipoR pairs yielded high FRET efficiencies in non-stimulated cells, which indicates that AdipoR1 and AdipoR2 form homo- and heteromeric complexes under resting conditions. Live FRET imaging suggested that both homo- and heteromeric AdipoR complexes dissociate in response to adiponectin, but heteromers separate faster than homomers. Finally, phosphorylation of AMP-activated protein kinase in response to adiponectin was delayed in cells wherein heteromer formation was favored. In sum, our findings indicate that AdipoR1 and AdipoR2 form homo- and heteromers that present unique interaction behaviors and signaling properties. This raises the possibility that the pleiotropic, tissue-dependent functions of adiponectin depend on the expression levels of AdipoR1 and AdipoR2 and, therefore, on the steady-state proportion of homo- and heteromeric complexes.

  17. Functional characterization of an alpha-factor-like Sordaria macrospora peptide pheromone and analysis of its interaction with its cognate receptor in Saccharomyces cerevisiae.

    Science.gov (United States)

    Mayrhofer, Severine; Pöggeler, Stefanie

    2005-04-01

    The homothallic filamentous ascomycete Sordaria macrospora possesses genes which are thought to encode two pheromone precursors and two seven-transmembrane pheromone receptors. The pheromone precursor genes are termed ppg1 and ppg2. The putative products derived from the gene sequence show structural similarity to the alpha-factor precursors and a-factor precursors of the yeast Saccharomyces cerevisiae. Likewise, sequence similarity has been found between the putative products of the pheromone receptor genes pre2 and pre1 and the S. cerevisiae Ste2p alpha-factor receptor and Ste3p a-factor receptor, respectively. To investigate whether the alpha-factor-like pheromone-receptor pair of S. macrospora is functional, a heterologous yeast assay was used. Our results show that the S. macrospora alpha-factor-like pheromone precursor PPG1 is processed into an active pheromone by yeast MATalpha cells. The S. macrospora PRE2 protein was demonstrated to be a peptide pheromone receptor. In yeast MATa cells lacking the endogenous Ste2p receptor, the S. macrospora PRE2 receptor facilitated all aspects of the pheromone response. Using a synthetic peptide, we can now predict the sequence of one active form of the S. macrospora peptide pheromone. We proved that S. macrospora wild-type strains secrete an active pheromone into the culture medium and that disruption of the ppg1 gene in S. macrospora prevents pheromone production. However, loss of the ppg1 gene does not affect vegetative growth or fertility. Finally, we established the yeast assay as an easy and useful system for analyzing pheromone production in developmental mutants of S. macrospora.

  18. Measuring agricultural policy bias

    DEFF Research Database (Denmark)

    Jensen, Henning Tarp; Robinson, Sherman; Tarp, Finn

    2010-01-01

    Measurement is a key issue in the literature on price incentive bias induced by trade policy. We introduce a general equilibrium measure of the relative effective rate of protection, which generalizes earlier protection measures. For our fifteen sample countries, results indicate that the agricul...

  19. A C-terminal segment of the V{sub 1}R vasopressin receptor is unstructured in the crystal structure of its chimera with the maltose-binding protein

    Energy Technology Data Exchange (ETDEWEB)

    Adikesavan, Nallini Vijayarangan; Mahmood, Syed Saad; Stanley, Nithianantham; Xu, Zhen; Wu, Nan [Department of Biochemistry, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106-4935 (United States); Thibonnier, Marc [Department of Medicine, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106-4935 (United States); Shoham, Menachem, E-mail: mxs10@case.edu [Department of Biochemistry, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106-4935 (United States)

    2005-04-01

    The 1.8 Å crystal structure of an MBP-fusion protein with the C-terminal cytoplasmic segment of the V1 vasopressin receptor reveals that the receptor segment is unstructured. The V{sub 1} vascular vasopressin receptor (V{sub 1}R) is a G-protein-coupled receptor (GPCR) involved in the regulation of body-fluid osmolality, blood volume and blood pressure. Signal transduction is mediated by the third intracellular loop of this seven-transmembrane protein as well as by the C-terminal cytoplasmic segment. A chimera of the maltose-binding protein (MBP) and the C-terminal segment of V{sub 1}R has been cloned, expressed, purified and crystallized. The crystals belong to space group P2{sub 1}, with unit-cell parameters a = 51.10, b = 66.56, c = 115.72 Å, β = 95.99°. The 1.8 Å crystal structure reveals the conformation of MBP and part of the linker region of this chimera, with the C-terminal segment being unstructured. This may reflect a conformational plasticity in the C-terminal segment that may be necessary for proper function of V{sub 1}R.

  20. Obesity, the endocannabinoid system, and bias arising from pharmaceutical sponsorship.

    Science.gov (United States)

    McPartland, John M

    2009-01-01

    Previous research has shown that academic physicians conflicted by funding from the pharmaceutical industry have corrupted evidence based medicine and helped enlarge the market for drugs. Physicians made pharmaceutical-friendly statements, engaged in disease mongering, and signed biased review articles ghost-authored by corporate employees. This paper tested the hypothesis that bias affects review articles regarding rimonabant, an anti-obesity drug that blocks the central cannabinoid receptor. A MEDLINE search was performed for rimonabant review articles, limited to articles authored by USA physicians who served as consultants for the company that manufactures rimonabant. Extracted articles were examined for industry-friendly bias, identified by three methods: analysis with a validated instrument for monitoring bias in continuing medical education (CME); analysis for bias defined as statements that ran contrary to external evidence; and a tally of misrepresentations about the endocannabinoid system. Eight review articles were identified, but only three disclosed authors' financial conflicts of interest, despite easily accessible information to the contrary. The Takhar CME bias instrument demonstrated statistically significant bias in all the review articles. Biased statements that were nearly identical reappeared in the articles, including disease mongering, exaggerating rimonabant's efficacy and safety, lack of criticisms regarding rimonabant clinical trials, and speculations about surrogate markers stated as facts. Distinctive and identical misrepresentations regarding the endocannabinoid system also reappeared in articles by different authors. The findings are characteristic of bias that arises from financial conflicts of interest, and suggestive of ghostwriting by a common author. Resolutions for this scenario are proposed.

  1. Crystal structure of the ligand-bound glucagon-like peptide-1 receptor extracellular domain.

    Science.gov (United States)

    Runge, Steffen; Thøgersen, Henning; Madsen, Kjeld; Lau, Jesper; Rudolph, Rainer

    2008-04-25

    The glucagon-like peptide-1 receptor (GLP-1R) belongs to Family B1 of the seven-transmembrane G protein-coupled receptors, and its natural agonist ligand is the peptide hormone glucagon-like peptide-1 (GLP-1). GLP-1 is involved in glucose homeostasis, and activation of GLP-1R in the plasma membrane of pancreatic beta-cells potentiates glucose-dependent insulin secretion. The N-terminal extracellular domain (nGLP-1R) is an important ligand binding domain that binds GLP-1 and the homologous peptide Exendin-4 with differential affinity. Exendin-4 has a C-terminal extension of nine amino acid residues known as the "Trp cage", which is absent in GLP-1. The Trp cage was believed to interact with nGLP-1R and thereby explain the superior affinity of Exendin-4. However, the molecular details that govern ligand binding and specificity of nGLP-1R remain undefined. Here we report the crystal structure of human nGLP-1R in complex with the antagonist Exendin-4(9-39) solved by the multiwavelength anomalous dispersion method to 2.2A resolution. The structure reveals that Exendin-4(9-39) is an amphipathic alpha-helix forming both hydrophobic and hydrophilic interactions with nGLP-1R. The Trp cage of Exendin-4 is not involved in binding to nGLP-1R. The hydrophobic binding site of nGLP-1R is defined by discontinuous segments including primarily a well defined alpha-helix in the N terminus of nGLP-1R and a loop between two antiparallel beta-strands. The structure provides for the first time detailed molecular insight into ligand binding of the human GLP-1 receptor, an established target for treatment of type 2 diabetes.

  2. Insulin receptors

    International Nuclear Information System (INIS)

    Kahn, C.R.; Harrison, L.C.

    1988-01-01

    This book contains the proceedings on insulin receptors. Part A: Methods for the study of structure and function. Topics covered include: Method for purification and labeling of insulin receptors, the insulin receptor kinase, and insulin receptors on special tissues

  3. Estimation bias and bias correction in reduced rank autoregressions

    DEFF Research Database (Denmark)

    Nielsen, Heino Bohn

    2017-01-01

    This paper characterizes the finite-sample bias of the maximum likelihood estimator (MLE) in a reduced rank vector autoregression and suggests two simulation-based bias corrections. One is a simple bootstrap implementation that approximates the bias at the MLE. The other is an iterative root...

  4. The N-terminal domain of APJ, a CNS-based coreceptor for HIV-1, is essential for its receptor function and coreceptor activity

    International Nuclear Information System (INIS)

    Zhou Naiming; Zhang Xiaoling; Fan Xuejun; Argyris, Elias; Fang Jianhua; Acheampong, Edward; DuBois, Garrett C.; Pomerantz, Roger J.

    2003-01-01

    The human APJ, a G protein-coupled seven-transmembrane receptor, has been found to be dramatically expressed in the human central nervous system (CNS) and also to serve as a coreceptor for the entry of human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV). Studies with animal models suggested that APJ and its natural ligand, apelin, play an important role in the central control of body fluid homeostasis, and in regulation of blood pressure and cardiac contractility. In this study, we characterize the structural and functional determinants of the N-terminal domain of APJ in interactions with its natural ligand and HIV-1 envelope glycoprotein. We demonstrate that the second 10 residues of the N-terminal domain of APJ are critical for association with apelin, while the first 20 amino acids play an important role in supporting cell-cell fusion mediated by HIV-1 gp120. With site-directed mutagenesis, we have identified that the negatively charged amino acid residues Glu20 and Asp23 are involved in receptor and coreceptor functions, but residues Tyr10 and Tyr11 substantially contribute to coreceptor function for both T-tropic (CXCR4) and dual-tropic (CXCR4 and CCR5) HIV-1 isolates. Thus, this study provides potentially important information for further characterizing APJ-apelin functions in vitro and in vivo and designing small molecules for treatment of HIV-1 infection in the CNS

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

    Directory of Open Access Journals (Sweden)

    Jörg D Wichard

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

  6. Comparative analysis of the repertoire of G protein-coupled receptors of three species of the fungal genus Trichoderma

    Science.gov (United States)

    2013-01-01

    Background Eukaryotic organisms employ cell surface receptors such as the seven-transmembrane G protein-coupled receptors (GPCRs) as sensors to connect to the environment. GPCRs react to a variety of extracellular cues and are considered to play central roles in the signal transduction in fungi. Several species of the filamentous ascomycete Trichoderma are potent mycoparasites, i.e. can attack and parasitize other fungi, which turns them into successful bio-fungicides for the protection of plants against fungal phytopathogens. The identification and characterization of GPCRs will provide insights into how Trichoderma communicates with its environment and senses the presence of host fungi. Results We mined the recently published genomes of the two mycoparasitic biocontrol agents Trichoderma atroviride and Trichoderma virens and compared the identified GPCR-like proteins to those of the saprophyte Trichoderma reesei. Phylogenetic analyses resulted in 14 classes and revealed differences not only among the three Trichoderma species but also between Trichoderma and other fungi. The class comprising proteins of the PAQR family was significantly expanded both in Trichoderma compared to other fungi as well as in the two mycoparasites compared to T. reesei. Expression analysis of the PAQR-encoding genes of the three Trichoderma species revealed that all except one were actually transcribed. Furthermore, the class of receptors with a DUF300 domain was expanded in T. atroviride, and T. virens showed an expansion of PTH11-like receptors compared to T. atroviride and T. reesei. Conclusions Comparative genome analyses of three Trichoderma species revealed a great diversity of putative GPCRs with genus- and species- specific differences. The expansion of certain classes in the mycoparasites T. atroviride and T. virens is likely to reflect the capability of these fungi to establish various ecological niches and interactions with other organisms such as fungi and plants. These

  7. Comparative analysis of the repertoire of G protein-coupled receptors of three species of the fungal genus Trichoderma.

    Science.gov (United States)

    Gruber, Sabine; Omann, Markus; Zeilinger, Susanne

    2013-05-16

    Eukaryotic organisms employ cell surface receptors such as the seven-transmembrane G protein-coupled receptors (GPCRs) as sensors to connect to the environment. GPCRs react to a variety of extracellular cues and are considered to play central roles in the signal transduction in fungi. Several species of the filamentous ascomycete Trichoderma are potent mycoparasites, i.e. can attack and parasitize other fungi, which turns them into successful bio-fungicides for the protection of plants against fungal phytopathogens. The identification and characterization of GPCRs will provide insights into how Trichoderma communicates with its environment and senses the presence of host fungi. We mined the recently published genomes of the two mycoparasitic biocontrol agents Trichoderma atroviride and Trichoderma virens and compared the identified GPCR-like proteins to those of the saprophyte Trichoderma reesei. Phylogenetic analyses resulted in 14 classes and revealed differences not only among the three Trichoderma species but also between Trichoderma and other fungi. The class comprising proteins of the PAQR family was significantly expanded both in Trichoderma compared to other fungi as well as in the two mycoparasites compared to T. reesei. Expression analysis of the PAQR-encoding genes of the three Trichoderma species revealed that all except one were actually transcribed. Furthermore, the class of receptors with a DUF300 domain was expanded in T. atroviride, and T. virens showed an expansion of PTH11-like receptors compared to T. atroviride and T. reesei. Comparative genome analyses of three Trichoderma species revealed a great diversity of putative GPCRs with genus- and species- specific differences. The expansion of certain classes in the mycoparasites T. atroviride and T. virens is likely to reflect the capability of these fungi to establish various ecological niches and interactions with other organisms such as fungi and plants. These GPCRs consequently represent

  8. Genetic variants of the unsaturated fatty acid receptor GPR120 relating to obesity in dogs.

    Science.gov (United States)

    Miyabe, Masahiro; Gin, Azusa; Onozawa, Eri; Daimon, Mana; Yamada, Hana; Oda, Hitomi; Mori, Akihiro; Momota, Yutaka; Azakami, Daigo; Yamamoto, Ichiro; Mochizuki, Mariko; Sako, Toshinori; Tamura, Katsutoshi; Ishioka, Katsumi

    2015-10-01

    G protein-coupled receptor (GPR) 120 is an unsaturated fatty acid receptor, which is associated with various physiological functions. It is reported that the genetic variant of GPR120, p.Arg270His, is detected more in obese people, and this genetic variation functionally relates to obesity in humans. Obesity is a common nutritional disorder also in dogs, but the genetic factors have not ever been identified in dogs. In this study, we investigated the molecular structure of canine GPR120 and searched for candidate genetic variants which may relate to obesity in dogs. Canine GPR120 was highly homologous to those of other species, and seven transmembrane domains and two N-glycosylation sites were conserved. GPR120 mRNA was expressed in lung, jejunum, ileum, colon, hypothalamus, hippocampus, spinal cord, bone marrow, dermis and white adipose tissues in dogs, as those in mice and humans. Genetic variants of GPR120 were explored in client-owned 141 dogs, resulting in that 5 synonymous and 4 non-synonymous variants were found. The variant c.595C>A (p.Pro199Thr) was found in 40 dogs, and the gene frequency was significantly higher in dogs with higher body condition scores, i.e. 0.320 in BCS4-5 dogs, 0.175 in BCS3 dogs and 0.000 in BCS2 dogs. We conclude that c.595C>A (p.Pro199Thr) is a candidate variant relating to obesity, which may be helpful for nutritional management of dogs.

  9. Structure modeling of all identified G protein-coupled receptors in the human genome.

    Science.gov (United States)

    Zhang, Yang; Devries, Mark E; Skolnick, Jeffrey

    2006-02-01

    G protein-coupled receptors (GPCRs), encoded by about 5% of human genes, comprise the largest family of integral membrane proteins and act as cell surface receptors responsible for the transduction of endogenous signal into a cellular response. Although tertiary structural information is crucial for function annotation and drug design, there are few experimentally determined GPCR structures. To address this issue, we employ the recently developed threading assembly refinement (TASSER) method to generate structure predictions for all 907 putative GPCRs in the human genome. Unlike traditional homology modeling approaches, TASSER modeling does not require solved homologous template structures; moreover, it often refines the structures closer to native. These features are essential for the comprehensive modeling of all human GPCRs when close homologous templates are absent. Based on a benchmarked confidence score, approximately 820 predicted models should have the correct folds. The majority of GPCR models share the characteristic seven-transmembrane helix topology, but 45 ORFs are predicted to have different structures. This is due to GPCR fragments that are predominantly from extracellular or intracellular domains as well as database annotation errors. Our preliminary validation includes the automated modeling of bovine rhodopsin, the only solved GPCR in the Protein Data Bank. With homologous templates excluded, the final model built by TASSER has a global C(alpha) root-mean-squared deviation from native of 4.6 angstroms, with a root-mean-squared deviation in the transmembrane helix region of 2.1 angstroms. Models of several representative GPCRs are compared with mutagenesis and affinity labeling data, and consistent agreement is demonstrated. Structure clustering of the predicted models shows that GPCRs with similar structures tend to belong to a similar functional class even when their sequences are diverse. These results demonstrate the usefulness and robustness

  10. Structure modeling of all identified G protein-coupled receptors in the human genome.

    Directory of Open Access Journals (Sweden)

    Yang Zhang

    2006-02-01

    Full Text Available G protein-coupled receptors (GPCRs, encoded by about 5% of human genes, comprise the largest family of integral membrane proteins and act as cell surface receptors responsible for the transduction of endogenous signal into a cellular response. Although tertiary structural information is crucial for function annotation and drug design, there are few experimentally determined GPCR structures. To address this issue, we employ the recently developed threading assembly refinement (TASSER method to generate structure predictions for all 907 putative GPCRs in the human genome. Unlike traditional homology modeling approaches, TASSER modeling does not require solved homologous template structures; moreover, it often refines the structures closer to native. These features are essential for the comprehensive modeling of all human GPCRs when close homologous templates are absent. Based on a benchmarked confidence score, approximately 820 predicted models should have the correct folds. The majority of GPCR models share the characteristic seven-transmembrane helix topology, but 45 ORFs are predicted to have different structures. This is due to GPCR fragments that are predominantly from extracellular or intracellular domains as well as database annotation errors. Our preliminary validation includes the automated modeling of bovine rhodopsin, the only solved GPCR in the Protein Data Bank. With homologous templates excluded, the final model built by TASSER has a global C(alpha root-mean-squared deviation from native of 4.6 angstroms, with a root-mean-squared deviation in the transmembrane helix region of 2.1 angstroms. Models of several representative GPCRs are compared with mutagenesis and affinity labeling data, and consistent agreement is demonstrated. Structure clustering of the predicted models shows that GPCRs with similar structures tend to belong to a similar functional class even when their sequences are diverse. These results demonstrate the usefulness

  11. The Second Transmembrane Domain of the Human Type 1 Angiotensin II Receptor Participates in the Formation of the Ligand Binding Pocket and Undergoes Integral Pivoting Movement during the Process of Receptor Activation*

    Science.gov (United States)

    Domazet, Ivana; Holleran, Brian J.; Martin, Stéphane S.; Lavigne, Pierre; Leduc, Richard; Escher, Emanuel; Guillemette, Gaétan

    2009-01-01

    The octapeptide hormone angiotensin II (AngII) exerts a wide variety of cardiovascular effects through the activation of the angiotensin II type-1 (AT1) receptor, which belongs to the G protein-coupled receptor superfamily. Like other G protein-coupled receptors, the AT1 receptor possesses seven transmembrane domains that provide structural support for the formation of the ligand-binding pocket. In order to identify those residues in the second transmembrane domain (TMD2) that contribute to the formation of the binding pocket of the AT1 receptor, we used the substituted cysteine accessibility method. All of the residues within the Leu-70 to Trp-94 region were mutated one at a time to a cysteine, and, after expression in COS-7 cells, the mutant receptors were treated with the sulfhydryl-specific alkylating agent methanethiosulfonate-ethylammonium (MTSEA). MTSEA reacts selectively with water-accessible, free sulfhydryl groups of endogenous or introduced point mutation cysteines. If a cysteine is found in the binding pocket, the covalent modification will affect the binding kinetics of the ligand. MTSEA substantially decreased the binding affinity of D74C-AT1, L81C-AT1, A85C-AT1, T88C-AT1, and A89C-AT1 mutant receptors, which suggests that these residues orient themselves within the water-accessible binding pocket of the AT1 receptor. Interestingly, this pattern of acquired MTSEA sensitivity was altered for TMD2 reporter cysteines engineered in a constitutively active N111G-AT1 receptor background. Indeed, mutant D74C-N111G-AT1 became insensitive to MTSEA, whereas mutant L81C-N111G-AT1 lost some sensitivity and mutant V86C-N111G-AT1 became sensitive to MTSEA. Our results suggest that constitutive activation of the AT1 receptor causes TMD2 to pivot, bringing the top of TMD2 closer to the binding pocket and pushing the bottom of TMD2 away from the binding pocket. PMID:19276075

  12. The second transmembrane domain of the human type 1 angiotensin II receptor participates in the formation of the ligand binding pocket and undergoes integral pivoting movement during the process of receptor activation.

    Science.gov (United States)

    Domazet, Ivana; Holleran, Brian J; Martin, Stéphane S; Lavigne, Pierre; Leduc, Richard; Escher, Emanuel; Guillemette, Gaétan

    2009-05-01

    The octapeptide hormone angiotensin II (AngII) exerts a wide variety of cardiovascular effects through the activation of the angiotensin II type-1 (AT(1)) receptor, which belongs to the G protein-coupled receptor superfamily. Like other G protein-coupled receptors, the AT(1) receptor possesses seven transmembrane domains that provide structural support for the formation of the ligand-binding pocket. In order to identify those residues in the second transmembrane domain (TMD2) that contribute to the formation of the binding pocket of the AT(1) receptor, we used the substituted cysteine accessibility method. All of the residues within the Leu-70 to Trp-94 region were mutated one at a time to a cysteine, and, after expression in COS-7 cells, the mutant receptors were treated with the sulfhydryl-specific alkylating agent methanethiosulfonate-ethylammonium (MTSEA). MTSEA reacts selectively with water-accessible, free sulfhydryl groups of endogenous or introduced point mutation cysteines. If a cysteine is found in the binding pocket, the covalent modification will affect the binding kinetics of the ligand. MTSEA substantially decreased the binding affinity of D74C-AT(1), L81C-AT(1), A85C-AT(1), T88C-AT(1), and A89C-AT(1) mutant receptors, which suggests that these residues orient themselves within the water-accessible binding pocket of the AT(1) receptor. Interestingly, this pattern of acquired MTSEA sensitivity was altered for TMD2 reporter cysteines engineered in a constitutively active N111G-AT(1) receptor background. Indeed, mutant D74C-N111G-AT(1) became insensitive to MTSEA, whereas mutant L81C-N111G-AT(1) lost some sensitivity and mutant V86C-N111G-AT(1) became sensitive to MTSEA. Our results suggest that constitutive activation of the AT(1) receptor causes TMD2 to pivot, bringing the top of TMD2 closer to the binding pocket and pushing the bottom of TMD2 away from the binding pocket.

  13. Exchange bias theory

    International Nuclear Information System (INIS)

    Kiwi, Miguel

    2001-01-01

    Research on the exchange bias (EB) phenomenon has witnessed a flurry of activity during recent years, which stems from its use in magnetic sensors and as stabilizers in magnetic reading heads. EB was discovered in 1956 but it attracted only limited attention until these applications, closely related to giant magnetoresistance, were developed during the last decade. In this review, I initially give a short introduction, listing the most salient experimental results and what is required from an EB theory. Next, I indicate some of the obstacles in the road towards a satisfactory understanding of the phenomenon. The main body of the text reviews and critically discusses the activity that has flourished, mainly during the last 5 years, in the theoretical front. Finally, an evaluation of the progress made, and a critical assessment as to where we stand nowadays along the road to a satisfactory theory, is presented

  14. Bias modification training can alter approach bias and chocolate consumption.

    Science.gov (United States)

    Schumacher, Sophie E; Kemps, Eva; Tiggemann, Marika

    2016-01-01

    Recent evidence has demonstrated that bias modification training has potential to reduce cognitive biases for attractive targets and affect health behaviours. The present study investigated whether cognitive bias modification training could be applied to reduce approach bias for chocolate and affect subsequent chocolate consumption. A sample of 120 women (18-27 years) were randomly assigned to an approach-chocolate condition or avoid-chocolate condition, in which they were trained to approach or avoid pictorial chocolate stimuli, respectively. Training had the predicted effect on approach bias, such that participants trained to approach chocolate demonstrated an increased approach bias to chocolate stimuli whereas participants trained to avoid such stimuli showed a reduced bias. Further, participants trained to avoid chocolate ate significantly less of a chocolate muffin in a subsequent taste test than participants trained to approach chocolate. Theoretically, results provide support for the dual process model's conceptualisation of consumption as being driven by implicit processes such as approach bias. In practice, approach bias modification may be a useful component of interventions designed to curb the consumption of unhealthy foods. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Evidence of positive selection at codon sites localized in extracellular domains of mammalian CC motif chemokine receptor proteins

    Directory of Open Access Journals (Sweden)

    Metzger Kelsey J

    2010-05-01

    Full Text Available Abstract Background CC chemokine receptor proteins (CCR1 through CCR10 are seven-transmembrane G-protein coupled receptors whose signaling pathways are known for their important roles coordinating immune system responses through targeted trafficking of white blood cells. In addition, some of these receptors have been identified as fusion proteins for viral pathogens: for example, HIV-1 strains utilize CCR5, CCR2 and CCR3 proteins to obtain cellular entry in humans. The extracellular domains of these receptor proteins are involved in ligand-binding specificity as well as pathogen recognition interactions. In mammals, the majority of chemokine receptor genes are clustered together; in humans, seven of the ten genes are clustered in the 3p21-24 chromosome region. Gene conversion events, or exchange of DNA sequence between genes, have been reported in chemokine receptor paralogs in various mammalian lineages, especially between the cytogenetically closely located pairs CCR2/5 and CCR1/3. Datasets of mammalian orthologs for each gene were analyzed separately to minimize the potential confounding impact of analyzing highly similar sequences resulting from gene conversion events. Molecular evolution approaches and the software package Phylogenetic Analyses by Maximum Likelihood (PAML were utilized to investigate the signature of selection that has acted on the mammalian CC chemokine receptor (CCR gene family. The results of neutral vs. adaptive evolution (positive selection hypothesis testing using Site Models are reported. In general, positive selection is defined by a ratio of nonsynonymous/synonymous nucleotide changes (dN/dS, or ω >1. Results Of the ten mammalian CC motif chemokine receptor sequence datasets analyzed, only CCR2 and CCR3 contain amino acid codon sites that exhibit evidence of positive selection using site based hypothesis testing in PAML. Nineteen of the twenty codon sites putatively indentified as likely to be under positive

  16. Stalk-dependent and Stalk-independent Signaling by the Adhesion G Protein-coupled Receptors GPR56 (ADGRG1) and BAI1 (ADGRB1).

    Science.gov (United States)

    Kishore, Ayush; Purcell, Ryan H; Nassiri-Toosi, Zahra; Hall, Randy A

    2016-02-12

    The adhesion G protein-coupled receptors (aGPCRs) are a large yet poorly understood family of seven-transmembrane proteins. A defining characteristic of the aGPCR family is the conserved GAIN domain, which has autoproteolytic activity and can cleave the receptors near the first transmembrane domain. Several aGPCRs, including ADGRB1 (BAI1 or B1) and ADGRG1 (GPR56 or G1), have been found to exhibit significantly increased constitutive activity when truncated to mimic GAIN domain cleavage (ΔNT). Recent reports have suggested that the new N-terminal stalk, which is revealed by GAIN domain cleavage, can directly activate aGPCRs as a tethered agonist. We tested this hypothesis in studies on two distinct aGPCRs, B1 and G1, by engineering mutant receptors lacking the entire NT including the stalk (B1- and G1-SL, with "SL" indicating "stalkless"). These receptors were evaluated in a battery of signaling assays and compared with full-length wild-type and cleavage-mimicking (ΔNT) forms of the two receptors. We found that B1-SL, in multiple assays, exhibited robust signaling activity, suggesting that the membrane-proximal stalk region is not necessary for its activation. For G1, however, the results were mixed, with the SL mutant exhibiting robust activity in several signaling assays (including TGFα shedding, activation of NFAT luciferase, and β-arrestin recruitment) but reduced activity relative to ΔNT in a distinct assay (activation of SRF luciferase). These data support a model in which the activation of certain pathways downstream of aGPCRs is stalk-dependent, whereas signaling to other pathways is stalk-independent. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  17. MIBE acts as antagonist ligand of both estrogen receptor α and GPER in breast cancer cells.

    Science.gov (United States)

    Lappano, Rosamaria; Santolla, Maria Francesca; Pupo, Marco; Sinicropi, Maria Stefania; Caruso, Anna; Rosano, Camillo; Maggiolini, Marcello

    2012-01-17

    The multiple biological responses to estrogens are mainly mediated by the classical estrogen receptors ERα and ERβ, which act as ligand-activated transcription factors. ERα exerts a main role in the development of breast cancer; therefore, the ER antagonist tamoxifen has been widely used although its effectiveness is limited by de novo and acquired resistance. Recently, GPR30/GPER, a member of the seven-transmembrane G protein-coupled receptor family, has been implicated in mediating the effects of estrogens in various normal and cancer cells. In particular, GPER triggered gene expression and proliferative responses induced by estrogens and even ER antagonists in hormone-sensitive tumor cells. Likewise, additional ER ligands showed the ability to bind to GPER eliciting promiscuous and, in some cases, opposite actions through the two receptors. We synthesized a novel compound (ethyl 3-[5-(2-ethoxycarbonyl-1-methylvinyloxy)-1-methyl-1H-indol-3-yl]but-2-enoate), referred to as MIBE, and investigated its properties elicited through ERα and GPER in breast cancer cells. Molecular modeling, binding experiments and functional assays were performed in order to evaluate the biological action exerted by MIBE through ERα and GPER in MCF7 and SkBr3 breast cancer cells. MIBE displayed the ability to act as an antagonist ligand for ERα and GPER as it elicited inhibitory effects on gene transcription and growth effects by binding to both receptors in breast cancer cells. Moreover, GPER was required for epidermal growth factor receptor (EGFR) and ERK activation by EGF as ascertained by using MIBE and performing gene silencing experiments. Our findings provide novel insights on the functional cross-talk between GPER and EGFR signaling. Furthermore, the exclusive antagonistic activity exerted by MIBE on ERα and GPER could represent an innovative pharmacological approach targeting breast carcinomas which express one or both receptors at the beginning and/or during tumor

  18. Religious Attitudes and Home Bias

    OpenAIRE

    C. Reggiani; G. Rossini

    2008-01-01

    Home bias affects trade in goods, services and financial assets. It is mostly generated by "natural" trade barriers. Among these dividers we may list many behavioral and sociological factors, such as status quo biases and a few kind of ‘embeddedness’. Unfortunately these factors are difficult to measure. An important part of ‘embeddedness’ may be related to religious attitudes. Is there any relation between economic home bias and religious attitudes at the individual tier? Our aim is to provi...

  19. Bias in clinical intervention research

    DEFF Research Database (Denmark)

    Gluud, Lise Lotte

    2006-01-01

    Research on bias in clinical trials may help identify some of the reasons why investigators sometimes reach the wrong conclusions about intervention effects. Several quality components for the assessment of bias control have been suggested, but although they seem intrinsically valid, empirical...... evidence is needed to evaluate their effects on the extent and direction of bias. This narrative review summarizes the findings of methodological studies on the influence of bias in clinical trials. A number of methodological studies suggest that lack of adequate randomization in published trial reports...

  20. Information environment, behavioral biases, and home bias in analysts’ recommendations

    DEFF Research Database (Denmark)

    Farooq, Omar; Taouss, Mohammed

    2012-01-01

    Can information environment of a firm explain home bias in analysts’ recommendations? Can the extent of agency problems explain optimism difference between foreign and local analysts? This paper answers these questions by documenting the effect of information environment on home bias in analysts’...

  1. Threat bias, not negativity bias, underpins differences in political ideology.

    Science.gov (United States)

    Lilienfeld, Scott O; Latzman, Robert D

    2014-06-01

    Although disparities in political ideology are rooted partly in dispositional differences, Hibbing et al.'s analysis paints with an overly broad brush. Research on the personality correlates of liberal-conservative differences points not to global differences in negativity bias, but to differences in threat bias, probably emanating from differences in fearfulness. This distinction bears implications for etiological research and persuasion efforts.

  2. Obesity, the endocannabinoid system, and bias arising from pharmaceutical sponsorship.

    Directory of Open Access Journals (Sweden)

    John M McPartland

    Full Text Available Previous research has shown that academic physicians conflicted by funding from the pharmaceutical industry have corrupted evidence based medicine and helped enlarge the market for drugs. Physicians made pharmaceutical-friendly statements, engaged in disease mongering, and signed biased review articles ghost-authored by corporate employees. This paper tested the hypothesis that bias affects review articles regarding rimonabant, an anti-obesity drug that blocks the central cannabinoid receptor.A MEDLINE search was performed for rimonabant review articles, limited to articles authored by USA physicians who served as consultants for the company that manufactures rimonabant. Extracted articles were examined for industry-friendly bias, identified by three methods: analysis with a validated instrument for monitoring bias in continuing medical education (CME; analysis for bias defined as statements that ran contrary to external evidence; and a tally of misrepresentations about the endocannabinoid system. Eight review articles were identified, but only three disclosed authors' financial conflicts of interest, despite easily accessible information to the contrary. The Takhar CME bias instrument demonstrated statistically significant bias in all the review articles. Biased statements that were nearly identical reappeared in the articles, including disease mongering, exaggerating rimonabant's efficacy and safety, lack of criticisms regarding rimonabant clinical trials, and speculations about surrogate markers stated as facts. Distinctive and identical misrepresentations regarding the endocannabinoid system also reappeared in articles by different authors.The findings are characteristic of bias that arises from financial conflicts of interest, and suggestive of ghostwriting by a common author. Resolutions for this scenario are proposed.

  3. Identification of a melatonin receptor type 1A gene ( AccMTNR1A) in Apis cerana cerana and its possible involvement in the response to low temperature stress

    Science.gov (United States)

    Li, Guilin; Zhang, Yanming; Ni, Yong; Wang, Ying; Xu, Baohua; Guo, Xingqi

    2018-04-01

    It is known that melatonin plays an indispensable role in the defense against some environment-induced stresses. The melatonin receptor (MTNR) is also closely linked to the environmental stress response in mammals. However, little is known about the function of the MTNR in insects, including honeybees. In this study, we identified a MTNR from Apis cerana cerana named AccMTNR1A, which contained a typical seven-transmembrane domain common to this family of receptors. A subcellular localization analysis showed that AccMTNR1A was localized in the cytomembrane. Additionally, we found that cold stress apparently boosted AccMTNR1A transcription, indicating that AccMTNR1A possibly connects to the cold stress response. The knockdown of AccMTNR1A attenuated the expression level of some genes associated with the cold stress response, suggesting that AccMTNR1A likely plays an analogous role with these genes during low temperature stress response. Moreover, silencing of AccMTNR1A also suppressed the transcription of some antioxidant genes, prompting the possibility that the response of AccMTNR1A to cold stress response may be related to antioxidant signaling pathways. Collectively, the findings presented here provide evidence that AccMTNR1A may play essential roles in protecting Apis cerana cerana from cold stress.

  4. A ligand channel through the G protein coupled receptor opsin.

    Directory of Open Access Journals (Sweden)

    Peter W Hildebrand

    Full Text Available The G protein coupled receptor rhodopsin contains a pocket within its seven-transmembrane helix (TM structure, which bears the inactivating 11-cis-retinal bound by a protonated Schiff-base to Lys296 in TM7. Light-induced 11-cis-/all-trans-isomerization leads to the Schiff-base deprotonated active Meta II intermediate. With Meta II decay, the Schiff-base bond is hydrolyzed, all-trans-retinal is released from the pocket, and the apoprotein opsin reloaded with new 11-cis-retinal. The crystal structure of opsin in its active Ops* conformation provides the basis for computational modeling of retinal release and uptake. The ligand-free 7TM bundle of opsin opens into the hydrophobic membrane layer through openings A (between TM1 and 7, and B (between TM5 and 6, respectively. Using skeleton search and molecular docking, we find a continuous channel through the protein that connects these two openings and comprises in its central part the retinal binding pocket. The channel traverses the receptor over a distance of ca. 70 A and is between 11.6 and 3.2 A wide. Both openings are lined with aromatic residues, while the central part is highly polar. Four constrictions within the channel are so narrow that they must stretch to allow passage of the retinal beta-ionone-ring. Constrictions are at openings A and B, respectively, and at Trp265 and Lys296 within the retinal pocket. The lysine enforces a 90 degrees elbow-like kink in the channel which limits retinal passage. With a favorable Lys side chain conformation, 11-cis-retinal can take the turn, whereas passage of the all-trans isomer would require more global conformational changes. We discuss possible scenarios for the uptake of 11-cis- and release of all-trans-retinal. If the uptake gate of 11-cis-retinal is assigned to opening B, all-trans is likely to leave through the same gate. The unidirectional passage proposed previously requires uptake of 11-cis-retinal through A and release of photolyzed all

  5. Heuristic Biases in Mathematical Reasoning

    Science.gov (United States)

    Inglis, Matthew; Simpson, Adrian

    2005-01-01

    In this paper we briefly describe the dual process account of reasoning, and explain the role of heuristic biases in human thought. Concentrating on the so-called matching bias effect, we describe a piece of research that indicates a correlation between success at advanced level mathematics and an ability to override innate and misleading…

  6. Gender bias affects forests worldwide

    Science.gov (United States)

    Marlène Elias; Susan S Hummel; Bimbika S Basnett; Carol J.P. Colfer

    2017-01-01

    Gender biases persist in forestry research and practice. These biases result in reduced scientific rigor and inequitable, ineffective, and less efficient policies, programs, and interventions. Drawing from a two-volume collection of current and classic analyses on gender in forests, we outline five persistent and inter-related themes: gendered governance, tree tenure,...

  7. Anti-Bias Education: Reflections

    Science.gov (United States)

    Derman-Sparks, Louise

    2011-01-01

    It is 30 years since NAEYC published "Anti-Bias Curriculum Tools for Empowering Young Children" (Derman-Sparks & ABC Task Force, 1989). Since then, anti-bias education concepts have become part of the early childhood education (ECE) narrative in the United States and many other countries. It has brought a fresh way of thinking about…

  8. Large-scale galaxy bias

    Science.gov (United States)

    Desjacques, Vincent; Jeong, Donghui; Schmidt, Fabian

    2018-02-01

    This review presents a comprehensive overview of galaxy bias, that is, the statistical relation between the distribution of galaxies and matter. We focus on large scales where cosmic density fields are quasi-linear. On these scales, the clustering of galaxies can be described by a perturbative bias expansion, and the complicated physics of galaxy formation is absorbed by a finite set of coefficients of the expansion, called bias parameters. The review begins with a detailed derivation of this very important result, which forms the basis of the rigorous perturbative description of galaxy clustering, under the assumptions of General Relativity and Gaussian, adiabatic initial conditions. Key components of the bias expansion are all leading local gravitational observables, which include the matter density but also tidal fields and their time derivatives. We hence expand the definition of local bias to encompass all these contributions. This derivation is followed by a presentation of the peak-background split in its general form, which elucidates the physical meaning of the bias parameters, and a detailed description of the connection between bias parameters and galaxy statistics. We then review the excursion-set formalism and peak theory which provide predictions for the values of the bias parameters. In the remainder of the review, we consider the generalizations of galaxy bias required in the presence of various types of cosmological physics that go beyond pressureless matter with adiabatic, Gaussian initial conditions: primordial non-Gaussianity, massive neutrinos, baryon-CDM isocurvature perturbations, dark energy, and modified gravity. Finally, we discuss how the description of galaxy bias in the galaxies' rest frame is related to clustering statistics measured from the observed angular positions and redshifts in actual galaxy catalogs.

  9. Large-scale galaxy bias

    Science.gov (United States)

    Jeong, Donghui; Desjacques, Vincent; Schmidt, Fabian

    2018-01-01

    Here, we briefly introduce the key results of the recent review (arXiv:1611.09787), whose abstract is as following. This review presents a comprehensive overview of galaxy bias, that is, the statistical relation between the distribution of galaxies and matter. We focus on large scales where cosmic density fields are quasi-linear. On these scales, the clustering of galaxies can be described by a perturbative bias expansion, and the complicated physics of galaxy formation is absorbed by a finite set of coefficients of the expansion, called bias parameters. The review begins with a detailed derivation of this very important result, which forms the basis of the rigorous perturbative description of galaxy clustering, under the assumptions of General Relativity and Gaussian, adiabatic initial conditions. Key components of the bias expansion are all leading local gravitational observables, which include the matter density but also tidal fields and their time derivatives. We hence expand the definition of local bias to encompass all these contributions. This derivation is followed by a presentation of the peak-background split in its general form, which elucidates the physical meaning of the bias parameters, and a detailed description of the connection between bias parameters and galaxy (or halo) statistics. We then review the excursion set formalism and peak theory which provide predictions for the values of the bias parameters. In the remainder of the review, we consider the generalizations of galaxy bias required in the presence of various types of cosmological physics that go beyond pressureless matter with adiabatic, Gaussian initial conditions: primordial non-Gaussianity, massive neutrinos, baryon-CDM isocurvature perturbations, dark energy, and modified gravity. Finally, we discuss how the description of galaxy bias in the galaxies' rest frame is related to clustering statistics measured from the observed angular positions and redshifts in actual galaxy catalogs.

  10. Somatostatin receptors

    DEFF Research Database (Denmark)

    Møller, Lars Neisig; Stidsen, Carsten Enggaard; Hartmann, Bolette

    2003-01-01

    functional units, receptors co-operate. The total receptor apparatus of individual cell types is composed of different-ligand receptors (e.g. SRIF and non-SRIF receptors) and co-expressed receptor subtypes (e.g. sst(2) and sst(5) receptors) in characteristic proportions. In other words, levels of individual......-peptides, receptor agonists and antagonists. Relatively long half lives, as compared to those of the endogenous ligands, have been paramount from the outset. Motivated by theoretical puzzles or the shortcomings of present-day diagnostics and therapy, investigators have also aimed to produce subtype...

  11. Cognitive Bias in Systems Verification

    Science.gov (United States)

    Larson, Steve

    2012-01-01

    Working definition of cognitive bias: Patterns by which information is sought and interpreted that can lead to systematic errors in decisions. Cognitive bias is used in diverse fields: Economics, Politics, Intelligence, Marketing, to name a few. Attempts to ground cognitive science in physical characteristics of the cognitive apparatus exceed our knowledge. Studies based on correlations; strict cause and effect is difficult to pinpoint. Effects cited in the paper and discussed here have been replicated many times over, and appear sound. Many biases have been described, but it is still unclear whether they are all distinct. There may only be a handful of fundamental biases, which manifest in various ways. Bias can effect system verification in many ways . Overconfidence -> Questionable decisions to deploy. Availability -> Inability to conceive critical tests. Representativeness -> Overinterpretation of results. Positive Test Strategies -> Confirmation bias. Debiasing at individual level very difficult. The potential effect of bias on the verification process can be managed, but not eliminated. Worth considering at key points in the process.

  12. Administrative bias in South Africa

    Directory of Open Access Journals (Sweden)

    E S Nwauche

    2005-01-01

    Full Text Available This article reviews the interpretation of section 6(2(aii of the Promotion of Administrative Justice Act which makes an administrator “biased or reasonably suspected of bias” a ground of judicial review. In this regard, the paper reviews the determination of administrative bias in South Africa especially highlighting the concept of institutional bias. The paper notes that inspite of the formulation of the bias ground of review the test for administrative bias is the reasonable apprehension test laid down in the case of President of South Africa v South African Rugby Football Union(2 which on close examination is not the same thing. Accordingly the paper urges an alternative interpretation that is based on the reasonable suspicion test enunciated in BTR Industries South Africa (Pty Ltd v Metal and Allied Workers Union and R v Roberts. Within this context, the paper constructs a model for interpreting the bias ground of review that combines the reasonable suspicion test as interpreted in BTR Industries and R v Roberts, the possibility of the waiver of administrative bias, the curative mechanism of administrative appeal as well as some level of judicial review exemplified by the jurisprudence of article 6(1 of the European Convention of Human Rights, especially in the light of the contemplation of the South African Magistrate Court as a jurisdictional route of judicial review.

  13. Critical Thinking and Cognitive Bias

    Directory of Open Access Journals (Sweden)

    Jeffrey Maynes

    2015-05-01

    Full Text Available Teaching critical thinking skill is a central pedagogical aim in many courses. These skills, it is hoped, will be both portable (applicable in a wide range of contexts and durable (not forgotten quickly. Yet, both of these virtues are challenged by pervasive and potent cognitive biases, such as motivated reasoning, false consensus bias and hindsight bias. In this paper, I argue that a focus on the development of metacognitive skill shows promise as a means to inculcate debiasing habits in students. Such habits will help students become more critical reasoners. I close with suggestions for implementing this strategy.

  14. Functional Characterization of MC1R-TUBB3 Intergenic Splice Variants of the Human Melanocortin 1 Receptor.

    Directory of Open Access Journals (Sweden)

    Cecilia Herraiz

    Full Text Available The melanocortin 1 receptor gene (MC1R expressed in melanocytes is a major determinant of skin pigmentation. It encodes a Gs protein-coupled receptor activated by α-melanocyte stimulating hormone (αMSH. Human MC1R has an inefficient poly(A site allowing intergenic splicing with its downstream neighbour Tubulin-β-III (TUBB3. Intergenic splicing produces two MC1R isoforms, designated Iso1 and Iso2, bearing the complete seven transmembrane helices from MC1R fused to TUBB3-derived C-terminal extensions, in-frame for Iso1 and out-of-frame for Iso2. It has been reported that exposure to ultraviolet radiation (UVR might promote an isoform switch from canonical MC1R (MC1R-001 to the MC1R-TUBB3 chimeras, which might lead to novel phenotypes required for tanning. We expressed the Flag epitope-tagged intergenic isoforms in heterologous HEK293T cells and human melanoma cells, for functional characterization. Iso1 was expressed with the expected size. Iso2 yielded a doublet of Mr significantly lower than predicted, and impaired intracellular stability. Although Iso1- and Iso2 bound radiolabelled agonist with the same affinity as MC1R-001, their plasma membrane expression was strongly reduced. Decreased surface expression mostly resulted from aberrant forward trafficking, rather than high rates of endocytosis. Functional coupling of both isoforms to cAMP was lower than wild-type, but ERK activation upon binding of αMSH was unimpaired, suggesting imbalanced signaling from the splice variants. Heterodimerization of differentially labelled MC1R-001 with the splicing isoforms analyzed by co-immunoprecipitation was efficient and caused decreased surface expression of binding sites. Thus, UVR-induced MC1R isoforms might contribute to fine-tune the tanning response by modulating MC1R-001 availability and functional parameters.

  15. Comparative sequence and structural analyses of G-protein-coupled receptor crystal structures and implications for molecular models.

    Directory of Open Access Journals (Sweden)

    Catherine L Worth

    Full Text Available BACKGROUND: Up until recently the only available experimental (high resolution structure of a G-protein-coupled receptor (GPCR was that of bovine rhodopsin. In the past few years the determination of GPCR structures has accelerated with three new receptors, as well as squid rhodopsin, being successfully crystallized. All share a common molecular architecture of seven transmembrane helices and can therefore serve as templates for building molecular models of homologous GPCRs. However, despite the common general architecture of these structures key differences do exist between them. The choice of which experimental GPCR structure(s to use for building a comparative model of a particular GPCR is unclear and without detailed structural and sequence analyses, could be arbitrary. The aim of this study is therefore to perform a systematic and detailed analysis of sequence-structure relationships of known GPCR structures. METHODOLOGY: We analyzed in detail conserved and unique sequence motifs and structural features in experimentally-determined GPCR structures. Deeper insight into specific and important structural features of GPCRs as well as valuable information for template selection has been gained. Using key features a workflow has been formulated for identifying the most appropriate template(s for building homology models of GPCRs of unknown structure. This workflow was applied to a set of 14 human family A GPCRs suggesting for each the most appropriate template(s for building a comparative molecular model. CONCLUSIONS: The available crystal structures represent only a subset of all possible structural variation in family A GPCRs. Some GPCRs have structural features that are distributed over different crystal structures or which are not present in the templates suggesting that homology models should be built using multiple templates. This study provides a systematic analysis of GPCR crystal structures and a consistent method for identifying

  16. Comparative sequence and structural analyses of G-protein-coupled receptor crystal structures and implications for molecular models.

    Science.gov (United States)

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

    2009-09-16

    Up until recently the only available experimental (high resolution) structure of a G-protein-coupled receptor (GPCR) was that of bovine rhodopsin. In the past few years the determination of GPCR structures has accelerated with three new receptors, as well as squid rhodopsin, being successfully crystallized. All share a common molecular architecture of seven transmembrane helices and can therefore serve as templates for building molecular models of homologous GPCRs. However, despite the common general architecture of these structures key differences do exist between them. The choice of which experimental GPCR structure(s) to use for building a comparative model of a particular GPCR is unclear and without detailed structural and sequence analyses, could be arbitrary. The aim of this study is therefore to perform a systematic and detailed analysis of sequence-structure relationships of known GPCR structures. We analyzed in detail conserved and unique sequence motifs and structural features in experimentally-determined GPCR structures. Deeper insight into specific and important structural features of GPCRs as well as valuable information for template selection has been gained. Using key features a workflow has been formulated for identifying the most appropriate template(s) for building homology models of GPCRs of unknown structure. This workflow was applied to a set of 14 human family A GPCRs suggesting for each the most appropriate template(s) for building a comparative molecular model. The available crystal structures represent only a subset of all possible structural variation in family A GPCRs. Some GPCRs have structural features that are distributed over different crystal structures or which are not present in the templates suggesting that homology models should be built using multiple templates. This study provides a systematic analysis of GPCR crystal structures and a consistent method for identifying suitable templates for GPCR homology modelling that will

  17. Sparse "1"3C labelling for solid-state NMR studies of P. pastoris expressed eukaryotic seven-transmembrane proteins

    International Nuclear Information System (INIS)

    Liu, Jing; Liu, Chang; Fan, Ying; Munro, Rachel A.; Ladizhansky, Vladimir; Brown, Leonid S.; Wang, Shenlin

    2016-01-01

    We demonstrate a novel sparse "1"3C labelling approach for methylotrophic yeast P. pastoris expression system, towards solid-state NMR studies of eukaryotic membrane proteins. The labelling scheme was achieved by co-utilizing natural abundance methanol and specifically "1"3C labelled glycerol as carbon sources in the expression medium. This strategy improves the spectral resolution by 1.5 fold, displays site-specific labelling patterns, and has advantages for collecting long-range distance restraints for structure determination of large eukaryotic membrane proteins by solid-state NMR.

  18. Preferences, country bias, and international trade

    NARCIS (Netherlands)

    S. Roy (Santanu); J.M.A. Viaene (Jean-Marie)

    1998-01-01

    textabstractAnalyzes international trade where consumer preferences exhibit country bias. Why country biases arise; How trade can occur in the presence of country bias; Implication for the pattern of trade and specialization.

  19. Negativity Bias in Dangerous Drivers.

    Directory of Open Access Journals (Sweden)

    Jing Chai

    Full Text Available The behavioral and cognitive characteristics of dangerous drivers differ significantly from those of safe drivers. However, differences in emotional information processing have seldom been investigated. Previous studies have revealed that drivers with higher anger/anxiety trait scores are more likely to be involved in crashes and that individuals with higher anger traits exhibit stronger negativity biases when processing emotions compared with control groups. However, researchers have not explored the relationship between emotional information processing and driving behavior. In this study, we examined the emotional information processing differences between dangerous drivers and safe drivers. Thirty-eight non-professional drivers were divided into two groups according to the penalty points that they had accrued for traffic violations: 15 drivers with 6 or more points were included in the dangerous driver group, and 23 drivers with 3 or fewer points were included in the safe driver group. The emotional Stroop task was used to measure negativity biases, and both behavioral and electroencephalograph data were recorded. The behavioral results revealed stronger negativity biases in the dangerous drivers than in the safe drivers. The bias score was correlated with self-reported dangerous driving behavior. Drivers with strong negativity biases reported having been involved in mores crashes compared with the less-biased drivers. The event-related potentials (ERPs revealed that the dangerous drivers exhibited reduced P3 components when responding to negative stimuli, suggesting decreased inhibitory control of information that is task-irrelevant but emotionally salient. The influence of negativity bias provides one possible explanation of the effects of individual differences on dangerous driving behavior and traffic crashes.

  20. Numerical value biases sound localization.

    Science.gov (United States)

    Golob, Edward J; Lewald, Jörg; Getzmann, Stephan; Mock, Jeffrey R

    2017-12-08

    Speech recognition starts with representations of basic acoustic perceptual features and ends by categorizing the sound based on long-term memory for word meaning. However, little is known about whether the reverse pattern of lexical influences on basic perception can occur. We tested for a lexical influence on auditory spatial perception by having subjects make spatial judgments of number stimuli. Four experiments used pointing or left/right 2-alternative forced choice tasks to examine perceptual judgments of sound location as a function of digit magnitude (1-9). The main finding was that for stimuli presented near the median plane there was a linear left-to-right bias for localizing smaller-to-larger numbers. At lateral locations there was a central-eccentric location bias in the pointing task, and either a bias restricted to the smaller numbers (left side) or no significant number bias (right side). Prior number location also biased subsequent number judgments towards the opposite side. Findings support a lexical influence on auditory spatial perception, with a linear mapping near midline and more complex relations at lateral locations. Results may reflect coding of dedicated spatial channels, with two representing lateral positions in each hemispace, and the midline area represented by either their overlap or a separate third channel.

  1. News Consumption and Media Bias

    OpenAIRE

    Yi Xiang; Miklos Sarvary

    2007-01-01

    Bias in the market for news is well-documented. Recent research in economics explains the phenomenon by assuming that consumers want to read (watch) news that is consistent with their tastes or prior beliefs rather than the truth. The present paper builds on this idea but recognizes that (i) besides “biased” consumers, there are also “conscientious” consumers whose sole interest is in discovering the truth, and (ii) consistent with reality, media bias is constrained by the truth. These two fa...

  2. Biased limiter experiments on text

    International Nuclear Information System (INIS)

    Phillips, P.E.; Wootton, A.J.; Rowan, W.L.; Ritz, C.P.; Rhodes, T.L.; Bengtson, R.D.; Hodge, W.L.; Durst, R.D.; McCool, S.C.; Richards, B.; Gentle, K.W.; Schoch, P.; Forster, J.C.; Hickok, R.L.; Evans, T.E.

    1987-01-01

    Experiments using an electrically biased limiter have been performed on the Texas Experimental Tokamak (TEXT). A small movable limiter is inserted past the main poloidal ring limiter (which is electrically connected to the vacuum vessel) and biased at V Lim with respect to it. The floating potential, plasma potential and shear layer position can be controlled. With vertical strokeV Lim vertical stroke ≥ 50 V the plasma density increases. For V Lim Lim > 0 the results obtained are inconclusive. Variation of V Lim changes the electrostatic turbulence which may explain the observed total flux changes. (orig.)

  3. Gene : CBRC-DNOV-01-1811 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available _HUMAN 1e-69 68% ref|XP_588566.3| PREDICTED: similar to seven transmembrane helix receptor [Bos taurus] 2e-7...9 78% MQHCLSSWCPSWTLNSTLLCIFFLSHFSFLDLCFLSSIIPQLLVNLKCSDKSITYVDCMIQLYVSLVMGYTECIHLAVMTYDHYVAVCHPLHYIFFMHLWLRHVLASME

  4. Gene : CBRC-CPOR-01-1484 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available 2e-35 41% ref|XP_870944.1| PREDICTED: similar to seven transmembrane helix receptor [Bos taurus] 6e-71 60% M...SIPKATNQSKKITLHILFLSTLFIISNTLRQPRCPSMETCECAFYSSVVVPKLLENLLSKXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXLTRFRAVCHPLLYMVAY

  5. The coalitional value theory of antigay bias

    NARCIS (Netherlands)

    Winegard, Bo; Reynolds, Tania; Baumeister, Roy F.; Plant, E. Ashby

    2016-01-01

    Research indicates that antigay bias follows a specific pattern (and probably has throughout written history, at least in the West): (a) men evince more antigay bias than women; (b) men who belong to traditionally male coalitions evince more antigay bias than those who do not; (c) antigay bias is

  6. Biased Brownian dynamics for rate constant calculation.

    OpenAIRE

    Zou, G; Skeel, R D; Subramaniam, S

    2000-01-01

    An enhanced sampling method-biased Brownian dynamics-is developed for the calculation of diffusion-limited biomolecular association reaction rates with high energy or entropy barriers. Biased Brownian dynamics introduces a biasing force in addition to the electrostatic force between the reactants, and it associates a probability weight with each trajectory. A simulation loses weight when movement is along the biasing force and gains weight when movement is against the biasing force. The sampl...

  7. Exploring Attribution Theory and Bias

    Science.gov (United States)

    Robinson, Jessica A.

    2017-01-01

    Courses: This activity can be used in a wide range of classes, including interpersonal communication, introduction to communication, and small group communication. Objectives: After completing this activity, students should be able to: (1) define attribution theory, personality attribution, situational attribution, and attribution bias; (2)…

  8. Ratio Bias and Policy Preferences

    DEFF Research Database (Denmark)

    Pedersen, Rasmus Tue

    2016-01-01

    Numbers permeate modern political communication. While current scholarship on framing effects has focused on the persuasive effects of words and arguments, this article shows that framing of numbers can also substantially affect policy preferences. Such effects are caused by ratio bias, which...

  9. Bias in Peripheral Depression Biomarkers

    DEFF Research Database (Denmark)

    Carvalho, André F; Köhler, Cristiano A; Brunoni, André R

    2016-01-01

    BACKGROUND: To aid in the differentiation of individuals with major depressive disorder (MDD) from healthy controls, numerous peripheral biomarkers have been proposed. To date, no comprehensive evaluation of the existence of bias favoring the publication of significant results or inflating effect...

  10. Minimum Bias Trigger in ATLAS

    International Nuclear Information System (INIS)

    Kwee, Regina

    2010-01-01

    Since the restart of the LHC in November 2009, ATLAS has collected inelastic pp collisions to perform first measurements on charged particle densities. These measurements will help to constrain various models describing phenomenologically soft parton interactions. Understanding the trigger efficiencies for different event types are therefore crucial to minimize any possible bias in the event selection. ATLAS uses two main minimum bias triggers, featuring complementary detector components and trigger levels. While a hardware based first trigger level situated in the forward regions with 2.2 < |η| < 3.8 has been proven to select pp-collisions very efficiently, the Inner Detector based minimum bias trigger uses a random seed on filled bunches and central tracking detectors for the event selection. Both triggers were essential for the analysis of kinematic spectra of charged particles. Their performance and trigger efficiency measurements as well as studies on possible bias sources will be presented. We also highlight the advantage of these triggers for particle correlation analyses. (author)

  11. Gender bias in teaching evaluations

    NARCIS (Netherlands)

    Mengel, Friederike; Sauermann, Jan; Zölitz, Ulf Zoelitz

    2017-01-01

    This paper provides new evidence on gender bias in teaching evaluations. We exploit a quasi-experimental dataset of 19,952 student evaluations of university faculty in a context where students are randomly allocated to female or male instructors. Despite the fact that neither students’ grades nor

  12. Attentional Bias in Math Anxiety

    Directory of Open Access Journals (Sweden)

    Orly eRubinsten

    2015-10-01

    Full Text Available Cognitive theory from the field of general anxiety suggests that the tendency to display attentional bias toward negative information results in anxiety. Accordingly, the current study aims to investigate whether attentional bias is involved in math anxiety as well (i.e., a persistent negative reaction to math. Twenty seven participants (14 with high levels of math anxiety and 13 with low levels of math anxiety were presented with a novel computerized numerical version of the well established dot probe task. One of 6 types of prime stimuli, either math related or typically neutral, were presented on one side of a computer screen. The prime was preceded by a probe (either one or two asterisks that appeared in either the prime or the opposite location. Participants had to discriminate probe identity (one or two asterisks. Math anxious individuals reacted faster when the probe was at the location of the numerical related stimuli. This suggests the existence of attentional bias in math anxiety. That is, for math anxious individuals, the cognitive system selectively favored the processing of emotionally negative information (i.e., math related words. These findings suggest that attentional bias is linked to unduly intense math anxiety symptoms.

  13. Attentional bias in math anxiety.

    Science.gov (United States)

    Rubinsten, Orly; Eidlin, Hili; Wohl, Hadas; Akibli, Orly

    2015-01-01

    Cognitive theory from the field of general anxiety suggests that the tendency to display attentional bias toward negative information results in anxiety. Accordingly, the current study aims to investigate whether attentional bias is involved in math anxiety (MA) as well (i.e., a persistent negative reaction to math). Twenty seven participants (14 with high levels of MA and 13 with low levels of MA) were presented with a novel computerized numerical version of the well established dot probe task. One of six types of prime stimuli, either math related or typically neutral, was presented on one side of a computer screen. The prime was preceded by a probe (either one or two asterisks) that appeared in either the prime or the opposite location. Participants had to discriminate probe identity (one or two asterisks). Math anxious individuals reacted faster when the probe was at the location of the numerical related stimuli. This suggests the existence of attentional bias in MA. That is, for math anxious individuals, the cognitive system selectively favored the processing of emotionally negative information (i.e., math related words). These findings suggest that attentional bias is linked to unduly intense MA symptoms.

  14. Perception bias in route choice

    NARCIS (Netherlands)

    Vreeswijk, Jacob Dirk; Thomas, Tom; van Berkum, Eric C.; van Arem, Bart

    2014-01-01

    Travel time is probably one of the most studied attributes in route choice. Recently, perception of travel time received more attention as several studies have shown its importance in explaining route choice behavior. In particular, travel time estimates by travelers appear to be biased against

  15. Receptor assay

    Energy Technology Data Exchange (ETDEWEB)

    Kato, K; Ibayashi, H [Kyushu Univ., Fukuoka (Japan). Faculty of Medicine

    1975-05-01

    This paper summarized present status and problems of analysis of hormone receptor and a few considerations on clinical significance of receptor abnormalities. It was pointed that in future clinical field quantitative and qualitative analysis of receptor did not remain only in the etiological discussion, but that it was an epoch-making field of investigation which contained the possiblity of artificial change of sensitivity of living body on drugs and the development connected directly with treatment of various diseases.

  16. Superfamily of G-protein coupled receptors (GPCRs – extraordinary and outstanding success of evolution

    Directory of Open Access Journals (Sweden)

    Kazimierz Kochman

    2014-10-01

    Full Text Available The G protein-coupled receptors (GPCRs are considered as very diverse and also surprisingly successful structures during the whole evolutionary process, being capable of transducing the different forms of “information” within the cell and also between cells, such as different peptides, lipids, proteins, nucleotides, nucleosides, organic odorants and photons. Complex studies as well as two-dimensional crystallization of rhodopsin, their paradigm, led to the creation of a useful model having a common central core, consisting of seven transmembrane helical domains, which undergoes appropriate structural modification during activation and signal transduction. After the complete delineation of the human genome, which is the apogee of human scientific civilization and culture, it was possible to identify more than 800 human GPCR sequences and in parallel analyze 342 unique functional nonolfactory human GPCR sequences with phylogenetic analyses. These results support, with high bootstrap values, the existence of five main families, named by the authors glutamate, rhodopsin, adhesion, frizzle/taste2, and secretin, forming the GRAFS classification system. Positions of the GPCRs in chromosomal paralogous regions indicate the importance of tetraploidizations or local gene duplication events during their creation. Some families of GPCRs show, however, very little or no similarity in the sequence of amino acid chains. They utilize an enormous number of different domains to bind ligands and to activate the appropriate G-proteins. The delicate tuning of their coupling to G proteins is further regulated by splicing, RNA editing and phosphorylation. A number of GPCRs may also form homodimers or heterodimers with structurally different GPCRs and also with membrane-bound proteins having one transmembrane domain. It should also be stressed that not all GPCRs are strictly faithful to G proteins because growing evidence indicates that they can interact directly

  17. Follicle-stimulating hormone (FSH) activates extracellular signal-regulated kinase phosphorylation independently of beta-arrestin- and dynamin-mediated FSH receptor internalization

    Science.gov (United States)

    Piketty, Vincent; Kara, Elodie; Guillou, Florian; Reiter, Eric; Crepieux, Pascale

    2006-01-01

    Background The follicle-stimulating hormone receptor (FSH-R) is a seven transmembrane spanning receptor (7TMR) which plays a crucial role in male and female reproduction. Upon FSH stimulation, the FSH-R activates the extracellular signal-regulated kinases (ERK). However, the mechanisms whereby the agonist-stimulated FSH-R activates ERK are poorly understood. In order to activate ERK, some 7 TMRs require beta-arrestin-and dynamin-dependent internalization to occur, whereas some others do not. In the present study, we examined the ability of the FSH-activated FSH-R to induce ERK phosphorylation, in conditions where its beta-arrestin- and dynamin-mediated internalization was impaired. Methods Human embryonic kidney (HEK) 293 cells were transiently transfected with the rat FSH-R. Internalization of the FSH-R was manipulated by co-expression of either a beta-arrestin (319–418) dominant negative peptide, either an inactive dynamin K44A mutant or of wild-type beta-arrestin 1 or 2. The outcomes on the FSH-R internalization were assayed by measuring 125I-FSH binding at the cell surface when compared to internalized 125I-FSH binding. The resulting ERK phosphorylation level was visualized by Western blot analysis. Results In HEK 293 cells, FSH stimulated ERK phosphorylation in a dose-dependent manner. Co-transfection of the beta- arrestin (319–418) construct, or of the dynamin K44A mutant reduced FSH-R internalization in response to FSH, without affecting ERK phosphorylation. Likewise, overexpression of wild-type beta-arrestin 1 or 2 significantly increased the FSH-R internalization level in response to FSH, without altering FSH-induced ERK phosphorylation. Conclusion From these results, we conclude that the FSH-R does not require beta-arrestin- nor dynamin-mediated internalization to initiate ERK phosphorylation in response to FSH. PMID:16787538

  18. Variable-bias coin tossing

    International Nuclear Information System (INIS)

    Colbeck, Roger; Kent, Adrian

    2006-01-01

    Alice is a charismatic quantum cryptographer who believes her parties are unmissable; Bob is a (relatively) glamorous string theorist who believes he is an indispensable guest. To prevent possibly traumatic collisions of self-perception and reality, their social code requires that decisions about invitation or acceptance be made via a cryptographically secure variable-bias coin toss (VBCT). This generates a shared random bit by the toss of a coin whose bias is secretly chosen, within a stipulated range, by one of the parties; the other party learns only the random bit. Thus one party can secretly influence the outcome, while both can save face by blaming any negative decisions on bad luck. We describe here some cryptographic VBCT protocols whose security is guaranteed by quantum theory and the impossibility of superluminal signaling, setting our results in the context of a general discussion of secure two-party computation. We also briefly discuss other cryptographic applications of VBCT

  19. Probability biases as Bayesian inference

    Directory of Open Access Journals (Sweden)

    Andre; C. R. Martins

    2006-11-01

    Full Text Available In this article, I will show how several observed biases in human probabilistic reasoning can be partially explained as good heuristics for making inferences in an environment where probabilities have uncertainties associated to them. Previous results show that the weight functions and the observed violations of coalescing and stochastic dominance can be understood from a Bayesian point of view. We will review those results and see that Bayesian methods should also be used as part of the explanation behind other known biases. That means that, although the observed errors are still errors under the be understood as adaptations to the solution of real life problems. Heuristics that allow fast evaluations and mimic a Bayesian inference would be an evolutionary advantage, since they would give us an efficient way of making decisions. %XX In that sense, it should be no surprise that humans reason with % probability as it has been observed.

  20. Variable-bias coin tossing

    Science.gov (United States)

    Colbeck, Roger; Kent, Adrian

    2006-03-01

    Alice is a charismatic quantum cryptographer who believes her parties are unmissable; Bob is a (relatively) glamorous string theorist who believes he is an indispensable guest. To prevent possibly traumatic collisions of self-perception and reality, their social code requires that decisions about invitation or acceptance be made via a cryptographically secure variable-bias coin toss (VBCT). This generates a shared random bit by the toss of a coin whose bias is secretly chosen, within a stipulated range, by one of the parties; the other party learns only the random bit. Thus one party can secretly influence the outcome, while both can save face by blaming any negative decisions on bad luck. We describe here some cryptographic VBCT protocols whose security is guaranteed by quantum theory and the impossibility of superluminal signaling, setting our results in the context of a general discussion of secure two-party computation. We also briefly discuss other cryptographic applications of VBCT.

  1. Girl child and gender bias.

    Science.gov (United States)

    Chowdhry, D P

    1995-01-01

    This article identifies gender bias against female children and youth in India. Gender bias is based on centuries-old religious beliefs and sayings from ancient times. Discrimination is reflected in denial or ignorance of female children's educational, health, nutrition, and recreational needs. Female infanticide and selective abortion of female fetuses are other forms of discrimination. The task of eliminating or reducing gender bias will involve legal, developmental, political, and administrative measures. Public awareness needs to be created. There is a need to reorient the education and health systems and to advocate for gender equality. The government of India set the following goals for the 1990s: to protect the survival of the girl child and practice safe motherhood; to develop the girl child in general; and to protect vulnerable girl children in different circumstances and in special groups. The Health Authorities should monitor the laws carefully to assure marriage after the minimum age, ban sex determination of the fetus, and monitor the health and nutrition of pre-school girls and nursing and pregnant mothers. Mothers need to be encouraged to breast feed, and to breast feed equally between genders. Every village and slum area needs a mini health center. Maternal mortality must decline. Primary health centers and hospitals need more women's wards. Education must be universally accessible. Enrollments should be increased by educating rural tribal and slum parents, reducing distances between home and school, making curriculum more relevant to girls, creating more female teachers, and providing facilities and incentives for meeting the needs of girl students. Supplementary income could be provided to families for sending girls to school. Recreational activities must be free of gender bias. Dowry, sati, and devdasi systems should be banned.

  2. Competition and Commercial Media Bias

    OpenAIRE

    Blasco, Andrea; Sobbrio, Francesco

    2011-01-01

    This paper reviews the empirical evidence on commercial media bias (i.e., advertisers influence over media accuracy) and then introduces a simple model to summarize the main elements of the theoretical literature. The analysis provides three main policy insights for media regulators: i) Media regulators should target their monitoring efforts towards news contents upon which advertisers are likely to share similar preferences; ii) In advertising industries characterized by high correlation in ...

  3. BEHAVIORAL BIASES IN TRADING SECURITIES

    Directory of Open Access Journals (Sweden)

    Turcan Ciprian Sebastian

    2010-12-01

    Full Text Available The main thesis of this paper represents the importance and the effects that human behavior has over capital markets. It is important to see the link between the asset valuation and investor sentiment that motivate to pay for an asset a certain prices over/below the intrinsic value. The main behavioral aspects discussed are emotional factors such as: fear of regret, overconfidence, perseverance, loss aversion ,heuristic biases, misinformation and thinking errors, herding and their consequences.

  4. Significant biases affecting abundance determinations

    Science.gov (United States)

    Wesson, Roger

    2015-08-01

    I have developed two highly efficient codes to automate analyses of emission line nebulae. The tools place particular emphasis on the propagation of uncertainties. The first tool, ALFA, uses a genetic algorithm to rapidly optimise the parameters of gaussian fits to line profiles. It can fit emission line spectra of arbitrary resolution, wavelength range and depth, with no user input at all. It is well suited to highly multiplexed spectroscopy such as that now being carried out with instruments such as MUSE at the VLT. The second tool, NEAT, carries out a full analysis of emission line fluxes, robustly propagating uncertainties using a Monte Carlo technique.Using these tools, I have found that considerable biases can be introduced into abundance determinations if the uncertainty distribution of emission lines is not well characterised. For weak lines, normally distributed uncertainties are generally assumed, though it is incorrect to do so, and significant biases can result. I discuss observational evidence of these biases. The two new codes contain routines to correctly characterise the probability distributions, giving more reliable results in analyses of emission line nebulae.

  5. Galaxy formation and physical bias

    Science.gov (United States)

    Cen, Renyue; Ostriker, Jeremiah P.

    1992-01-01

    We have supplemented our code, which computes the evolution of the physical state of a representative piece of the universe to include, not only the dynamics of dark matter (with a standard PM code), and the hydrodynamics of the gaseous component (including detailed collisional and radiative processes), but also galaxy formation on a heuristic but plausible basis. If, within a cell the gas is Jeans' unstable, collapsing, and cooling rapidly, it is transformed to galaxy subunits, which are then followed with a collisionless code. After grouping them into galaxies, we estimate the relative distributions of galaxies and dark matter and the relative velocities of galaxies and dark matter. In a large scale CDM run of 80/h Mpc size with 8 x 10 exp 6 cells and dark matter particles, we find that physical bias b is on the 8/h Mpc scale is about 1.6 and increases towards smaller scales, and that velocity bias is about 0.8 on the same scale. The comparable HDM simulation is highly biased with b = 2.7 on the 8/h Mpc scale. Implications of these results are discussed in the light of the COBE observations which provide an accurate normalization for the initial power spectrum. CDM can be ruled out on the basis of too large a predicted small scale velocity dispersion at greater than 95 percent confidence level.

  6. Opinion dynamics with confirmation bias.

    Directory of Open Access Journals (Sweden)

    Armen E Allahverdyan

    Full Text Available Confirmation bias is the tendency to acquire or evaluate new information in a way that is consistent with one's preexisting beliefs. It is omnipresent in psychology, economics, and even scientific practices. Prior theoretical research of this phenomenon has mainly focused on its economic implications possibly missing its potential connections with broader notions of cognitive science.We formulate a (non-Bayesian model for revising subjective probabilistic opinion of a confirmationally-biased agent in the light of a persuasive opinion. The revision rule ensures that the agent does not react to persuasion that is either far from his current opinion or coincides with it. We demonstrate that the model accounts for the basic phenomenology of the social judgment theory, and allows to study various phenomena such as cognitive dissonance and boomerang effect. The model also displays the order of presentation effect-when consecutively exposed to two opinions, the preference is given to the last opinion (recency or the first opinion (primacy -and relates recency to confirmation bias. Finally, we study the model in the case of repeated persuasion and analyze its convergence properties.The standard Bayesian approach to probabilistic opinion revision is inadequate for describing the observed phenomenology of persuasion process. The simple non-Bayesian model proposed here does agree with this phenomenology and is capable of reproducing a spectrum of effects observed in psychology: primacy-recency phenomenon, boomerang effect and cognitive dissonance. We point out several limitations of the model that should motivate its future development.

  7. Matrilateral Bias in Human Grandmothering

    Directory of Open Access Journals (Sweden)

    Martin Daly

    2017-09-01

    Full Text Available Children receive more care and resources from their maternal grandmothers than from their paternal grandmothers. This asymmetry is the “matrilateral bias” in grandmaternal investment. Here, we synopsize the evolutionary theories that predict such a bias, and review evidence of its cross-cultural generality and magnitude. Evolutionists have long maintained that investing in a daughter’s child yields greater fitness returns, on average, than investing in a son’s child because of paternity uncertainty: the son’s putative progeny may have been sired by someone else. Recent theoretical work has identified an additional natural selective basis for the matrilateral bias that may be no less important: supporting grandchildren lightens the load on their mother, increasing her capacity to pursue her fitness in other ways, and if she invests those gains either in her natal relatives or in children of a former or future partner, fitness returns accrue to the maternal, but not the paternal, grandmother. In modern democracies, where kinship is reckoned bilaterally and no postmarital residence norms restrict grandmaternal access to grandchildren, many studies have found large matrilateral biases in contact, childcare, and emotional closeness. In other societies, patrilineal ideology and postmarital residence with the husband’s kin (virilocality might be expected to have produced a patrilateral bias instead, but the available evidence refutes this hypothesis. In hunter-gatherers, regardless of professed norms concerning kinship and residence, mothers get needed help at and after childbirth from their mothers, not their mothers-in-law. In traditional agricultural and pastoral societies, patrilineal and virilocal norms are common, but young mothers still turn to their natal families for crucial help, and several studies have documented benefits, including reduced child mortality, associated with access to maternal, but not paternal, grandmothers. Even

  8. Bias-correction in vector autoregressive models

    DEFF Research Database (Denmark)

    Engsted, Tom; Pedersen, Thomas Quistgaard

    2014-01-01

    We analyze the properties of various methods for bias-correcting parameter estimates in both stationary and non-stationary vector autoregressive models. First, we show that two analytical bias formulas from the existing literature are in fact identical. Next, based on a detailed simulation study......, we show that when the model is stationary this simple bias formula compares very favorably to bootstrap bias-correction, both in terms of bias and mean squared error. In non-stationary models, the analytical bias formula performs noticeably worse than bootstrapping. Both methods yield a notable...... improvement over ordinary least squares. We pay special attention to the risk of pushing an otherwise stationary model into the non-stationary region of the parameter space when correcting for bias. Finally, we consider a recently proposed reduced-bias weighted least squares estimator, and we find...

  9. The Probability Distribution for a Biased Spinner

    Science.gov (United States)

    Foster, Colin

    2012-01-01

    This article advocates biased spinners as an engaging context for statistics students. Calculating the probability of a biased spinner landing on a particular side makes valuable connections between probability and other areas of mathematics. (Contains 2 figures and 1 table.)

  10. Short Communication: Gender Bias and Stigmatization against ...

    African Journals Online (AJOL)

    Short Communication: Gender Bias and Stigmatization against Women Living with ... In Ethiopia, HIV/AIDS is highly stigmatized due to the fact that sexual ... bias, socio-economic situations and traditional beliefs contribute, individually and in ...

  11. Is there bias in editorial choice? Yes

    OpenAIRE

    Moustafa, Khaled

    2018-01-01

    Nature has recently published a Correspondence claiming the absence of fame biases in the editorial choice. The topic is interesting and deserves a deeper analysis than it was presented because the reported brief analysis and its conclusion are somewhat biased for many reasons, some of them are discussed here. Since the editorial assessment is a form of peer-review, the biases reported on external peer-reviews would, thus, apply to the editorial assessment, too. The biases would be proportion...

  12. Bias-field equalizer for bubble memories

    Science.gov (United States)

    Keefe, G. E.

    1977-01-01

    Magnetoresistive Perm-alloy sensor monitors bias field required to maintain bubble memory. Sensor provides error signal that, in turn, corrects magnitude of bias field. Error signal from sensor can be used to control magnitude of bias field in either auxiliary set of bias-field coils around permanent magnet field, or current in small coils used to remagnetize permanent magnet by infrequent, short, high-current pulse or short sequence of pulses.

  13. The Accuracy Enhancing Effect of Biasing Cues

    NARCIS (Netherlands)

    W. Vanhouche (Wouter); S.M.J. van Osselaer (Stijn)

    2009-01-01

    textabstractExtrinsic cues such as price and irrelevant attributes have been shown to bias consumers’ product judgments. Results in this article replicate those findings in pretrial judgments but show that such biasing cues can improve quality judgments at a later point in time. Initially biasing

  14. Biased managers, organizational design, and incentive provision

    OpenAIRE

    Moreira, Humberto Ataíde; Costa, Cristiano Machado; Ferreira, Daniel Bernardo Soares

    2004-01-01

    Rio de Janeiro We model the tradeoff between the balance and the strength of incentives implicit in the choice between hierarchical and matrix organizational structures. We show that managerial biases determine which structure is optimal: hierarchical forms are preferred when biases are low, while matrix structures are preferred when biases are high.

  15. An inclusive taxonomy of behavioral biases

    Directory of Open Access Journals (Sweden)

    David Peón

    2017-07-01

    Full Text Available This paper overviews the theoretical and empirical research on behavioral biases and their influence in the literature. To provide a systematic exposition, we present a unified framework that takes the reader through an original taxonomy, based on the reviews of relevant authors in the field. In particular, we establish three broad categories that may be distinguished: heuristics and biases; choices, values and frames; and social factors. We then describe the main biases within each category, and revise the main theoretical and empirical developments, linking each bias with other biases and anomalies that are related to them, according to the literature.

  16. Gender Bias Affects Forests Worldwide

    Directory of Open Access Journals (Sweden)

    Marlène Elias

    2017-04-01

    Full Text Available Gender biases persist in forestry research and practice. These biases result in reduced scientific rigor and inequitable, ineffective, and less efficient policies, programs, and interventions. Drawing from a two-volume collection of current and classic analyses on gender in forests, we outline five persistent and inter-related themes: gendered governance, tree tenure, forest spaces, division of labor, and ecological knowledge. Each emerges across geographic regions in the northern and southern hemisphere and reflects inequities in women’s and men’s ability to make decisions about and benefit from trees, forests, and their products. Women’s ability to participate in community-based forest governance is typically less than men’s, causing concern for social equity and forest stewardship. Women’s access to trees and their products is commonly more limited than men’s, and mediated by their relationship with their male counterparts. Spatial patterns of forest use reflect gender norms and taboos, and men’s greater access to transportation. The division of labor results in gender specialization in the collection of forest products, with variations in gender roles across regions. All these gender differences result in ecological knowledge that is distinct but also complementary and shifting across the genders. The ways gender plays out in relation to each theme may vary across cultures and contexts, but the influence of gender, which intersects with other factors of social differentiation in shaping forest landscapes, is global.

  17. Workplace ageism: discovering hidden bias.

    Science.gov (United States)

    Malinen, Sanna; Johnston, Lucy

    2013-01-01

    BACKGROUND/STUDY CONTEXT: Research largely shows no performance differences between older and younger employees, or that older workers even outperform younger employees, yet negative attitudes towards older workers can underpin discrimination. Unfortunately, traditional "explicit" techniques for assessing attitudes (i.e., self-report measures) have serious drawbacks. Therefore, using an approach that is novel to organizational contexts, the authors supplemented explicit with implicit (indirect) measures of attitudes towards older workers, and examined the malleability of both. This research consists of two studies. The authors measured self-report (explicit) attitudes towards older and younger workers with a survey, and implicit attitudes with a reaction-time-based measure of implicit associations. In addition, to test whether attitudes were malleable, the authors measured attitudes before and after a mental imagery intervention, where the authors asked participants in the experimental group to imagine respected and valued older workers from their surroundings. Negative, stable implicit attitudes towards older workers emerged in two studies. Conversely, explicit attitudes showed no age bias and were more susceptible to change intervention, such that attitudes became more positive towards older workers following the experimental manipulation. This research demonstrates the unconscious nature of bias against older workers, and highlights the utility of implicit attitude measures in the context of the workplace. In the current era of aging workforce and skill shortages, implicit measures may be necessary to illuminate hidden workplace ageism.

  18. Female-biased anorexia and anxiety in the Syrian hamster.

    Science.gov (United States)

    Shannonhouse, John L; Fong, Li An; Clossen, Bryan L; Hairgrove, Ross E; York, Daniel C; Walker, Benjamin B; Hercules, Gregory W; Mertesdorf, Lauren M; Patel, Margi; Morgan, Caurnel

    2014-06-22

    Anorexia and anxiety cause significant mortality and disability with female biases and frequent comorbidity after puberty, but the scarcity of suitable animal models impedes understanding of their biological underpinnings. It is reported here that in adult or weanling Syrian hamsters, relative to social housing (SH), social separation (SS) induced anorexia characterized as hypophagia, weight loss, reduced adiposity, and hypermetabolism. Following anorexia, SS increased reluctance to feed, and thigmotaxis, in anxiogenic environments. Importantly, anorexia and anxiety were induced post-puberty with female biases. SS also reduced hypothalamic corticotrophin-releasing factor mRNA and serum corticosteroid levels assessed by RT-PCR and RIA, respectively. Consistent with the view that sex differences in adrenal suppression contributed to female biases in anorexia and anxiety by disinhibiting neuroimmune activity, SS elevated hypothalamic interleukin-6 and toll-like receptor 4 mRNA levels. Although corticosteroids were highest during SH, they were within the physiological range and associated with juvenile-like growth of white adipose, bone, and skeletal muscle. These results suggest that hamsters exhibit plasticity in bioenergetic and emotional phenotypes across puberty without an increase in stress responsiveness. Thus, social separation of hamsters provides a model of sex differences in anorexia and anxiety during adulthood and their pathogeneses during adolescence. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Expression of the fructose receptor BmGr9 and its involvement in the promotion of feeding, suggested by its co-expression with neuropeptide F1 in Bombyx mori.

    Science.gov (United States)

    Mang, Dingze; Shu, Min; Tanaka, Shiho; Nagata, Shinji; Takada, Tomoyuki; Endo, Haruka; Kikuta, Shingo; Tabunoki, Hiroko; Iwabuchi, Kikuo; Sato, Ryoichi

    2016-08-01

    Insect gustatory receptors (Grs) are members of a large family of proteins with seven transmembrane domains that provide insects with the ability to detect chemical signals critical for feeding, mating, and oviposition. To date, 69 Bombyx mori Grs (BmGrs) genes have been identified via genome studies. BmGr9 has been shown to respond specifically to fructose and to function as a ligand-gated ion channel selectively activated by fructose. However, the sites where this Gr are expressed remain unclear. We demonstrated using reverse transcription (RT)-PCR that BmGr9 is widely expressed in the central nervous system (CNS), as well as oral sensory organs. Additionally, immunohistochemistry was performed using anti-BmGr9 antiserum to show that BmGr9 is expressed in cells of the oral sensory organs, including the maxillary galea, maxillary palps, labrum, and labium, as well as in putative neurosecretory cells of the CNS. Furthermore, double immunohistochemical analysis showed that most BmGr9-expressing cells co-localized with putative neuropeptide F1-expressing cells in the brain, suggesting that BmGr9 is involved in the promotion of feeding behaviors. In addition, a portion of BmGr9-expressing cells in the brain co-localized with cells expressing BmGr6, a molecule of the sugar receptor clade, suggesting that sugars other than fructose are involved in the regulation of feeding behaviors in B. mori larvae. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Social reward shapes attentional biases.

    Science.gov (United States)

    Anderson, Brian A

    2016-01-01

    Paying attention to stimuli that predict a reward outcome is important for an organism to survive and thrive. When visual stimuli are associated with tangible, extrinsic rewards such as money or food, these stimuli acquire high attentional priority and come to automatically capture attention. In humans and other primates, however, many behaviors are not motivated directly by such extrinsic rewards, but rather by the social feedback that results from performing those behaviors. In the present study, I examine whether positive social feedback can similarly influence attentional bias. The results show that stimuli previously associated with a high probability of positive social feedback elicit value-driven attentional capture, much like stimuli associated with extrinsic rewards. Unlike with extrinsic rewards, however, such stimuli also influence task-specific motivation. My findings offer a potential mechanism by which social reward shapes the information that we prioritize when perceiving the world around us.

  1. Ratio Bias and Policy Preferences

    DEFF Research Database (Denmark)

    Pedersen, Rasmus Tue

    2017-01-01

    Numbers permeate modern political communication. While current scholarship on framing effects has focused on the persuasive effects of words and arguments, this article shows that framing of numbers can also substantially affect policy preferences. Such effects are caused by ratio bias, which...... is a general tendency to focus on numerators and pay insufficient attention to denominators in ratios. Using a population-based survey experiment, I demonstrate how differently framed but logically equivalent representations of the exact same numerical value can have large effects on citizens’ preferences...... regarding salient political issues such as education and taxes. Furthermore, the effects of numerical framing are found across most groups of the population, largely regardless of their political predisposition and their general ability to understand and use numerical information. These findings have...

  2. Good practices for quantitative bias analysis.

    Science.gov (United States)

    Lash, Timothy L; Fox, Matthew P; MacLehose, Richard F; Maldonado, George; McCandless, Lawrence C; Greenland, Sander

    2014-12-01

    Quantitative bias analysis serves several objectives in epidemiological research. First, it provides a quantitative estimate of the direction, magnitude and uncertainty arising from systematic errors. Second, the acts of identifying sources of systematic error, writing down models to quantify them, assigning values to the bias parameters and interpreting the results combat the human tendency towards overconfidence in research results, syntheses and critiques and the inferences that rest upon them. Finally, by suggesting aspects that dominate uncertainty in a particular research result or topic area, bias analysis can guide efficient allocation of sparse research resources. The fundamental methods of bias analyses have been known for decades, and there have been calls for more widespread use for nearly as long. There was a time when some believed that bias analyses were rarely undertaken because the methods were not widely known and because automated computing tools were not readily available to implement the methods. These shortcomings have been largely resolved. We must, therefore, contemplate other barriers to implementation. One possibility is that practitioners avoid the analyses because they lack confidence in the practice of bias analysis. The purpose of this paper is therefore to describe what we view as good practices for applying quantitative bias analysis to epidemiological data, directed towards those familiar with the methods. We focus on answering questions often posed to those of us who advocate incorporation of bias analysis methods into teaching and research. These include the following. When is bias analysis practical and productive? How does one select the biases that ought to be addressed? How does one select a method to model biases? How does one assign values to the parameters of a bias model? How does one present and interpret a bias analysis?. We hope that our guide to good practices for conducting and presenting bias analyses will encourage

  3. Symmetry as Bias: Rediscovering Special Relativity

    Science.gov (United States)

    Lowry, Michael R.

    1992-01-01

    This paper describes a rational reconstruction of Einstein's discovery of special relativity, validated through an implementation: the Erlanger program. Einstein's discovery of special relativity revolutionized both the content of physics and the research strategy used by theoretical physicists. This research strategy entails a mutual bootstrapping process between a hypothesis space for biases, defined through different postulated symmetries of the universe, and a hypothesis space for physical theories. The invariance principle mutually constrains these two spaces. The invariance principle enables detecting when an evolving physical theory becomes inconsistent with its bias, and also when the biases for theories describing different phenomena are inconsistent. Structural properties of the invariance principle facilitate generating a new bias when an inconsistency is detected. After a new bias is generated. this principle facilitates reformulating the old, inconsistent theory by treating the latter as a limiting approximation. The structural properties of the invariance principle can be suitably generalized to other types of biases to enable primal-dual learning.

  4. Forecaster Behaviour and Bias in Macroeconomic Forecasts

    OpenAIRE

    Roy Batchelor

    2007-01-01

    This paper documents the presence of systematic bias in the real GDP and inflation forecasts of private sector forecasters in the G7 economies in the years 1990–2005. The data come from the monthly Consensus Economics forecasting service, and bias is measured and tested for significance using parametric fixed effect panel regressions and nonparametric tests on accuracy ranks. We examine patterns across countries and forecasters to establish whether the bias reflects the inefficient use of i...

  5. An inclusive taxonomy of behavioral biases

    OpenAIRE

    David Peón; Manel Antelo; Anxo Calvo-Silvosa

    2017-01-01

    This paper overviews the theoretical and empirical research on behavioral biases and their influence in the literature. To provide a systematic exposition, we present a unified framework that takes the reader through an original taxonomy, based on the reviews of relevant authors in the field. In particular, we establish three broad categories that may be distinguished: heuristics and biases; choices, values and frames; and social factors. We then describe the main biases within each category,...

  6. Cognitive Biases and Nonverbal Cue Availability in Detecting Deception

    Science.gov (United States)

    Burgoon, Judee K.; Blair, J. Pete; Strom, Renee E.

    2008-01-01

    In potentially deceptive situations, people rely on mental shortcuts to help process information. These heuristic judgments are often biased and result in inaccurate assessments of sender veracity. Four such biases--truth bias, visual bias, demeanor bias, and expectancy violation bias--were examined in a judgment experiment that varied nonverbal…

  7. Adaptable history biases in human perceptual decisions.

    Science.gov (United States)

    Abrahamyan, Arman; Silva, Laura Luz; Dakin, Steven C; Carandini, Matteo; Gardner, Justin L

    2016-06-21

    When making choices under conditions of perceptual uncertainty, past experience can play a vital role. However, it can also lead to biases that worsen decisions. Consistent with previous observations, we found that human choices are influenced by the success or failure of past choices even in a standard two-alternative detection task, where choice history is irrelevant. The typical bias was one that made the subject switch choices after a failure. These choice history biases led to poorer performance and were similar for observers in different countries. They were well captured by a simple logistic regression model that had been previously applied to describe psychophysical performance in mice. Such irrational biases seem at odds with the principles of reinforcement learning, which would predict exquisite adaptability to choice history. We therefore asked whether subjects could adapt their irrational biases following changes in trial order statistics. Adaptability was strong in the direction that confirmed a subject's default biases, but weaker in the opposite direction, so that existing biases could not be eradicated. We conclude that humans can adapt choice history biases, but cannot easily overcome existing biases even if irrational in the current context: adaptation is more sensitive to confirmatory than contradictory statistics.

  8. Attribution bias and social anxiety in schizophrenia

    Directory of Open Access Journals (Sweden)

    Amelie M. Achim

    2016-06-01

    Full Text Available Studies on attribution biases in schizophrenia have produced mixed results, whereas such biases have been more consistently reported in people with anxiety disorders. Anxiety comorbidities are frequent in schizophrenia, in particular social anxiety disorder, which could influence their patterns of attribution biases. The objective of the present study was thus to determine if individuals with schizophrenia and a comorbid social anxiety disorder (SZ+ show distinct attribution biases as compared with individuals with schizophrenia without social anxiety (SZ− and healthy controls. Attribution biases were assessed with the Internal, Personal, and Situational Attributions Questionnaire in 41 individual with schizophrenia and 41 healthy controls. Results revealed the lack of the normal externalizing bias in SZ+, whereas SZ− did not significantly differ from healthy controls on this dimension. The personalizing bias was not influenced by social anxiety but was in contrast linked with delusions, with a greater personalizing bias in individuals with current delusions. Future studies on attribution biases in schizophrenia should carefully document symptom presentation, including social anxiety.

  9. Biased lineups: sequential presentation reduces the problem.

    Science.gov (United States)

    Lindsay, R C; Lea, J A; Nosworthy, G J; Fulford, J A; Hector, J; LeVan, V; Seabrook, C

    1991-12-01

    Biased lineups have been shown to increase significantly false, but not correct, identification rates (Lindsay, Wallbridge, & Drennan, 1987; Lindsay & Wells, 1980; Malpass & Devine, 1981). Lindsay and Wells (1985) found that sequential lineup presentation reduced false identification rates, presumably by reducing reliance on relative judgment processes. Five staged-crime experiments were conducted to examine the effect of lineup biases and sequential presentation on eyewitness recognition accuracy. Sequential lineup presentation significantly reduced false identification rates from fair lineups as well as from lineups biased with regard to foil similarity, instructions, or witness attire, and from lineups biased in all of these ways. The results support recommendations that police present lineups sequentially.

  10. Dipole-induced exchange bias.

    Science.gov (United States)

    Torres, Felipe; Morales, Rafael; Schuller, Ivan K; Kiwi, Miguel

    2017-11-09

    The discovery of dipole-induced exchange bias (EB), switching from negative to positive sign, is reported in systems where the antiferromagnet and the ferromagnet are separated by a paramagnetic spacer (AFM-PM-FM). The magnitude and sign of the EB is determined by the cooling field strength and the PM thickness. The same cooling field yields negative EB for thin spacers, and positive EB for thicker ones. The EB decay profile as a function of the spacer thickness, and the change of sign, are attributed to long-ranged dipole coupling. Our model, which accounts quantitatively for the experimental results, ignores the short range interfacial exchange interactions of the usual EB theories. Instead, it retains solely the long range dipole field that allows for the coupling of the FM and AFM across the PM spacer. The experiments allow for novel switching capabilities of long range EB systems, while the theory allows description of the structures where the FM and AFM are not in atomic contact. The results provide a new approach to design novel interacting heterostructures.

  11. Media bias under direct and indirect government control: when is the bias smaller?

    OpenAIRE

    Abhra Roy

    2015-01-01

    We present an analytical framework to compare media bias under direct and indirect government control. In this context, we show that direct control can lead to a smaller bias and higher welfare than indirect control. We further show that the size of the advertising market affects media bias only under direct control. Media bias, under indirect control, is not affected by the size of the advertising market.

  12. Developmental Changes in the Whole Number Bias

    Science.gov (United States)

    Braithwaite, David W.; Siegler, Robert S.

    2018-01-01

    Many students' knowledge of fractions is adversely affected by whole number bias, the tendency to focus on the separate whole number components (numerator and denominator) of a fraction rather than on the fraction's magnitude (ratio of numerator to denominator). Although whole number bias appears early in the fraction learning process and under…

  13. Bounding the bias of contrastive divergence learning

    DEFF Research Database (Denmark)

    Fischer, Anja; Igel, Christian

    2011-01-01

    Optimization based on k-step contrastive divergence (CD) has become a common way to train restricted Boltzmann machines (RBMs). The k-step CD is a biased estimator of the log-likelihood gradient relying on Gibbs sampling. We derive a new upper bound for this bias. Its magnitude depends on k...

  14. Distinctive Characteristics of Sexual Orientation Bias Crimes

    Science.gov (United States)

    Stacey, Michele

    2011-01-01

    Despite increased attention in the area of hate crime research in the past 20 years, sexual orientation bias crimes have rarely been singled out for study. When these types of crimes are looked at, the studies are typically descriptive in nature. This article seeks to increase our knowledge of sexual orientation bias by answering the question:…

  15. Dialogue Games for Inconsistent and Biased Information

    NARCIS (Netherlands)

    Lebbink, H.J.; Witteman, C.L.M.; Meyer, J.J.C.

    2003-01-01

    In this article, a dialogue game is presented in which coherent conversational sequences with inconsistent and biased information are described at the speech act level. Inconsistent and biased information is represented with bilattice structures, and based on these bilattice structures, a

  16. Gender Bias: Inequities in the Classroom.

    Science.gov (United States)

    Love, Reeve

    1993-01-01

    This article explores sex bias in curricular materials for elementary and secondary schools. Sex bias is defined as a set of unconscious behaviors that, in themselves, are often trivial and generally favorable. Although these behaviors do not hurt if they happen only once, they can cause a great deal of harm if a pattern develops that serves to…

  17. The Battle over Studies of Faculty Bias

    Science.gov (United States)

    Gravois, John

    2007-01-01

    The American Federation of Teachers (AFT) recently commissioned a study to review the research that finds liberal bias run amok in academe. Believing that the AFT is not a dispassionate observer of this debate, this article provides "The Chronicle of Higher Education's" survey of the genre. The studies reviewed include: (1) "Political Bias in the…

  18. Production bias and cluster annihilation: Why necessary?

    DEFF Research Database (Denmark)

    Singh, B.N.; Trinkaus, H.; Woo, C.H.

    1994-01-01

    the primary cluster density is high. Therefore, a sustained high swelling rate driven by production bias must involve the annihilation of primary clusters at sinks. A number of experimental observations which are unexplainable in terms of the conventional dislocation bias for monointerstitials is considered......-field approach. The production bias approach, on the other hand, is based on the physical features of the cascade damage and is therefore considered to be more appropriate for describing the damage accumulation under cascade damage conditions. However, production bias can not produce high a swelling rate when....... It is found that the production bias and cluster annihilation are necessary to explain these observations, with, in many cases, the explicit consideration of the annihilation of the primary interstitial clusters....

  19. Investigating d-cycloserine as a potential pharmacological enhancer of an emotional bias learning procedure.

    Science.gov (United States)

    Woud, Marcella L; Blackwell, Simon E; Steudte-Schmiedgen, Susann; Browning, Michael; Holmes, Emily A; Harmer, Catherine J; Margraf, Jürgen; Reinecke, Andrea

    2018-05-01

    The partial N-methyl-D-aspartate receptor agonist d-cycloserine may enhance psychological therapies. However, its exact mechanism of action is still being investigated. Cognitive bias modification techniques allow isolation of cognitive processes and thus investigation of how they may be affected by d-cycloserine. We used a cognitive bias modification paradigm targeting appraisals of a stressful event, Cognitive Bias Modification-Appraisal, to investigate whether d-cycloserine enhanced the modification of appraisal, and whether it caused greater reduction in indices of psychopathology. Participants received either 250 mg of d-cycloserine ( n=19) or placebo ( n=19). As a stressor task, participants recalled a negative life event, followed by positive Cognitive Bias Modification-Appraisal training. Before and after Cognitive Bias Modification-Appraisal, appraisals and indices of psychopathology related to the stressor were assessed. Cognitive Bias Modification-Appraisal successfully modified appraisals, but d-cycloserine did not affect appraisals post-training. There were no post-training group differences in frequency of intrusions. Interestingly, d-cycloserine led to a greater reduction in distress and impact on state mood from recalling the event, and lower distress post-training was associated with fewer intrusions. Therefore, d-cycloserine may affect emotional reactivity to recalling a negative event when combined with induction of a positive appraisal style, but via a mechanism other than enhanced learning of the appraisal style.

  20. Gender bias in cardiovascular advertisements.

    Science.gov (United States)

    Ahmed, Sofia B; Grace, Sherry L; Stelfox, Henry Thomas; Tomlinson, George; Cheung, Angela M

    2004-11-01

    Women with cardiovascular disease are treated less aggressively than men. The reasons for this disparity are unclear. Pharmaceutical advertisements may influence physician practices and patient care. To determine if female and male patients are equally likely to be featured in cardiovascular advertisements. We examined all cardiovascular advertisements from US editions of general medical and cardiovascular journals published between 1 January 1996 and 30 June 1998. For each unique advertisement, we recorded the total number of journal appearances and the number of appearances in journals' premium positions. We noted the gender, age, race and role of both the primary figure and the majority of people featured in the advertisement. Nine hundred and nineteen unique cardiovascular advertisements were identified of which 254 depicted a patient as the primary figure. A total of 20%[95% confidence interval (CI) 15.3-25.5%] of these advertisements portrayed a female patient, while 80% (95% CI 74.5-84.7%) depicted a male patient, P advertisements appeared 249 times (13.3%; 95% CI 8.6-18.9%) while male patient advertisements appeared 1618 times (86.7%; 95% CI 81.1-91.4%), P advertisements also had significantly fewer mean appearances than male patient advertisements in journals' premium positions (0.82 vs. 1.99, P=0.02). Similar results were seen when the advertisements were analysed according to predominant gender. Despite increasing emphasis on cardiovascular disease in women, significant under-representation of female patients exists in cardiovascular advertisements. Physicians should be cognizant of this gender bias.

  1. Automation bias in electronic prescribing.

    Science.gov (United States)

    Lyell, David; Magrabi, Farah; Raban, Magdalena Z; Pont, L G; Baysari, Melissa T; Day, Richard O; Coiera, Enrico

    2017-03-16

    Clinical decision support (CDS) in e-prescribing can improve safety by alerting potential errors, but introduces new sources of risk. Automation bias (AB) occurs when users over-rely on CDS, reducing vigilance in information seeking and processing. Evidence of AB has been found in other clinical tasks, but has not yet been tested with e-prescribing. This study tests for the presence of AB in e-prescribing and the impact of task complexity and interruptions on AB. One hundred and twenty students in the final two years of a medical degree prescribed medicines for nine clinical scenarios using a simulated e-prescribing system. Quality of CDS (correct, incorrect and no CDS) and task complexity (low, low + interruption and high) were varied between conditions. Omission errors (failure to detect prescribing errors) and commission errors (acceptance of false positive alerts) were measured. Compared to scenarios with no CDS, correct CDS reduced omission errors by 38.3% (p < .0001, n = 120), 46.6% (p < .0001, n = 70), and 39.2% (p < .0001, n = 120) for low, low + interrupt and high complexity scenarios respectively. Incorrect CDS increased omission errors by 33.3% (p < .0001, n = 120), 24.5% (p < .009, n = 82), and 26.7% (p < .0001, n = 120). Participants made commission errors, 65.8% (p < .0001, n = 120), 53.5% (p < .0001, n = 82), and 51.7% (p < .0001, n = 120). Task complexity and interruptions had no impact on AB. This study found evidence of AB omission and commission errors in e-prescribing. Verification of CDS alerts is key to avoiding AB errors. However, interventions focused on this have had limited success to date. Clinicians should remain vigilant to the risks of CDS failures and verify CDS.

  2. Biases in GNSS-Data Processing

    Science.gov (United States)

    Schaer, S. C.; Dach, R.; Lutz, S.; Meindl, M.; Beutler, G.

    2010-12-01

    Within the Global Positioning System (GPS) traditionally different types of pseudo-range measurements (P-code, C/A-code) are available on the first frequency that are tracked by the receivers with different technologies. For that reason, P1-C1 and P1-P2 Differential Code Biases (DCB) need to be considered in a GPS data processing with a mix of different receiver types. Since the Block IIR-M series of GPS satellites also provide C/A-code on the second frequency, P2-C2 DCB need to be added to the list of biases for maintenance. Potential quarter-cycle biases between different phase observables (specifically L2P and L2C) are another issue. When combining GNSS (currently GPS and GLONASS), careful consideration of inter-system biases (ISB) is indispensable, in particular when an adequate combination of individual GLONASS clock correction results from different sources (using, e.g., different software packages) is intended. Facing the GPS and GLONASS modernization programs and the upcoming GNSS, like the European Galileo and the Chinese Compass, an increasing number of types of biases is expected. The Center for Orbit Determination in Europe (CODE) is monitoring these GPS and GLONASS related biases for a long time based on RINEX files of the tracking network of the International GNSS Service (IGS) and in the frame of the data processing as one of the global analysis centers of the IGS. Within the presentation we give an overview on the stability of the biases based on the monitoring. Biases derived from different sources are compared. Finally, we give an outlook on the potential handling of such biases with the big variety of signals and systems expected in the future.

  3. On the Limitations of Variational Bias Correction

    Science.gov (United States)

    Moradi, Isaac; Mccarty, Will; Gelaro, Ronald

    2018-01-01

    Satellite radiances are the largest dataset assimilated into Numerical Weather Prediction (NWP) models, however the data are subject to errors and uncertainties that need to be accounted for before assimilating into the NWP models. Variational bias correction uses the time series of observation minus background to estimate the observations bias. This technique does not distinguish between the background error, forward operator error, and observations error so that all these errors are summed up together and counted as observation error. We identify some sources of observations errors (e.g., antenna emissivity, non-linearity in the calibration, and antenna pattern) and show the limitations of variational bias corrections on estimating these errors.

  4. Cognitive biases and decision making in gambling.

    Science.gov (United States)

    Chóliz, Mariano

    2010-08-01

    Heuristics and cognitive biases can occur in reasoning and decision making. Some of them are very common in gamblers (illusion of control, representativeness, availability, etc.). Structural characteristics and functioning of games of chance favor the appearance of these biases. Two experiments were conducted with nonpathological gamblers. The first experiment was a game of dice with wagers. In the second experiment, the participants played two bingo games. Specific rules of the games favored the appearance of cognitive bias (illusion of control) and heuristics (representativeness and availability) and influence on the bets. Results and implications for gambling are discussed.

  5. Removing Malmquist bias from linear regressions

    Science.gov (United States)

    Verter, Frances

    1993-01-01

    Malmquist bias is present in all astronomical surveys where sources are observed above an apparent brightness threshold. Those sources which can be detected at progressively larger distances are progressively more limited to the intrinsically luminous portion of the true distribution. This bias does not distort any of the measurements, but distorts the sample composition. We have developed the first treatment to correct for Malmquist bias in linear regressions of astronomical data. A demonstration of the corrected linear regression that is computed in four steps is presented.

  6. Reducing status quo bias in choice experiments

    DEFF Research Database (Denmark)

    Bonnichsen, Ole; Ladenburg, Jacob

    In stated preference literature, the tendency to choose the alternative representing the status quo situation seems to exceed real life status quo effects. Accordingly, status quo bias can be a problem. In Choice Experiments, status quo bias is found to be strongly correlated with protest attitudes...... toward the cost attribute. If economic values are to be elicited, this problem is difficult to remedy. In a split sample framework we test a novel ex-ante entreaty aimed specifically at the cost attribute and find that it effectively reduces status quo bias and improves the internal validity...

  7. delta-biased Josephson tunnel junctions

    DEFF Research Database (Denmark)

    Monaco, R.; Mygind, Jesper; Koshelet, V.

    2010-01-01

    Abstract: The behavior of a long Josephson tunnel junction drastically depends on the distribution of the dc bias current. We investigate the case in which the bias current is fed in the central point of a one-dimensional junction. Such junction configuration has been recently used to detect...... the persistent currents circulating in a superconducting loop. Analytical and numerical results indicate that the presence of fractional vortices leads to remarkable differences from the conventional case of uniformly distributed dc bias current. The theoretical findings are supported by detailed measurements...

  8. A study on investors’ personality characteristics and behavioral biases: Conservatism bias and availability bias in the Tehran Stock Exchange

    Directory of Open Access Journals (Sweden)

    Mahmoud Moradi

    2013-04-01

    Full Text Available Most economic and finance theories are based on the assumption that during economic decision making, people would act totally rational and consider all available information. Nevertheless, behavioral finance focuses on studying of the role of psychological factors on economic participants’ behavior. The study shows that in real-world environment, people are influenced by emotional and cognitive errors and may make irrational financial decisions. In many cases, the participants of financial markets are not aware of their talents for error in decision making, so they are dissatisfied with their investments by considering some behavioral biases decisions. These decisions may often yield undesirable outcomes, which could influence economy, significantly. This paper presents a survey on the relationship between personality dimensions with behavioral biases and availability bias among investment managers in the Tehran Stock Exchange using SPSS software, descriptive and inferential statistics. The necessary data are collected through questionnaire and they are analyzed using some statistical tests. The preliminary results indicate that there is a relationship between personality dimensions and behavioral biases like conservatism bias and availability bias among the investors in the Tehran Stock Exchange.

  9. Identification and Characterization of Pheromone Receptors and Interplay between Receptors and Pheromone Binding Proteins in the Diamondback Moth, Plutella xyllostella

    OpenAIRE

    Sun, Mengjing; Liu, Yang; Walker, William B.; Liu, Chengcheng; Lin, Kejian; Gu, Shaohua; Zhang, Yongjun; Zhou, Jingjiang; Wang, Guirong

    2013-01-01

    Moths depend on olfactory cues such as sex pheromones to find and recognize mating partners. Pheromone receptors (PRs) and Pheromone binding proteins (PBPs) are thought to be associated with olfactory signal transduction of pheromonal compounds in peripheral olfactory reception. Here six candidate pheromone receptor genes in the diamondback moth, Plutella xyllostella were identified and cloned. All of the six candidate PR genes display male-biased expression, which is a typical characteristic...

  10. Students' gender bias in teaching evaluations

    Directory of Open Access Journals (Sweden)

    Narissra Punyanunt-Carter

    2015-09-01

    Full Text Available The goal of this study was to investigate if there is gender bias in student evaluations. Researchers administered a modified version of the teacher evaluation forms to 58 students (male=30; female=28 in a basic introductory communications class. Half the class was instructed to fill out the survey about a male professor, and the other half a female professor. Researchers broke down the evaluation results question by question in order to give a detailed account of the findings. Results revealed that there is certainly some gender bias at work when students evaluate their instructors. It was also found that gender bias does not significantly affect the evaluations. The results align with other findings in the available literature, which point to some sort of pattern regarding gender bias in evaluations, but it still seems to be inconsequential.  DOI: 10.18870/hlrc.v5i3.234

  11. Cognitive bias in symptomatic and recovered agoraphobics.

    Science.gov (United States)

    Stoler, L S; McNally, R J

    1991-01-01

    Symptomatic agoraphobics, recovered agoraphobics, and normal control subjects completed a series of sentence stems that had either ambiguous or unambiguous meanings, and had either a potentially threatening or a nonthreatening connotation. The written completions made by subjects to these stems were classified as indicating either a biased (i.e. threat-related) or unbiased interpretation of the meaning of the stem, and if a biased interpretation was made, whether the subject indicated efforts at adaptive coping with the perceived threat. Results indicated that symptomatic agoraphobics exhibited strong biases for interpreting information as threatening, relative to normal control subjects. Moreover, recovered agoraphobics resembled symptomatic agoraphobics more than normal control subjects, thus indicating that cognitive biases may persist following cessation of panic attacks and reductions in avoidance behavior. However, recovered agoraphobics also exhibited tendencies to cope adaptively with perceived threats whereas symptomatic agoraphobics did not.

  12. Galaxy bias and primordial non-Gaussianity

    Energy Technology Data Exchange (ETDEWEB)

    Assassi, Valentin; Baumann, Daniel [DAMTP, Cambridge University, Wilberforce Road, Cambridge CB3 0WA (United Kingdom); Schmidt, Fabian, E-mail: assassi@ias.edu, E-mail: D.D.Baumann@uva.nl, E-mail: fabians@MPA-Garching.MPG.DE [Max-Planck-Institut für Astrophysik, Karl-Schwarzschild-Str. 1, 85748 Garching (Germany)

    2015-12-01

    We present a systematic study of galaxy biasing in the presence of primordial non-Gaussianity. For a large class of non-Gaussian initial conditions, we define a general bias expansion and prove that it is closed under renormalization, thereby showing that the basis of operators in the expansion is complete. We then study the effects of primordial non-Gaussianity on the statistics of galaxies. We show that the equivalence principle enforces a relation between the scale-dependent bias in the galaxy power spectrum and that in the dipolar part of the bispectrum. This provides a powerful consistency check to confirm the primordial origin of any observed scale-dependent bias. Finally, we also discuss the imprints of anisotropic non-Gaussianity as motivated by recent studies of higher-spin fields during inflation.

  13. Accounting for Unobservable Exposure Time Bias Wh...

    Data.gov (United States)

    U.S. Department of Health & Human Services — Accounting for Unobservable Exposure Time Bias When Using Medicare Prescription Drug Data Unobservable exposure time is common among Medicare Part D beneficiaries,...

  14. Galaxy bias and primordial non-Gaussianity

    International Nuclear Information System (INIS)

    Assassi, Valentin; Baumann, Daniel; Schmidt, Fabian

    2015-01-01

    We present a systematic study of galaxy biasing in the presence of primordial non-Gaussianity. For a large class of non-Gaussian initial conditions, we define a general bias expansion and prove that it is closed under renormalization, thereby showing that the basis of operators in the expansion is complete. We then study the effects of primordial non-Gaussianity on the statistics of galaxies. We show that the equivalence principle enforces a relation between the scale-dependent bias in the galaxy power spectrum and that in the dipolar part of the bispectrum. This provides a powerful consistency check to confirm the primordial origin of any observed scale-dependent bias. Finally, we also discuss the imprints of anisotropic non-Gaussianity as motivated by recent studies of higher-spin fields during inflation

  15. Exchange bias studied with polarized neutron reflectivity

    International Nuclear Information System (INIS)

    Velthuis, S. G. E. te

    2000-01-01

    The role of Polarized Neutron Reflectivity (PNR) for studying natural and synthetic exchange biased systems is illustrated. For a partially oxidized thin film of Co, cycling of the magnetic field causes a considerable reduction of the bias, which the onset of diffuse neutron scattering shows to be due to the loosening of the ferromagnetic domains. On the other hand, PNR measurements of a model exchange bias junction consisting of an n-layered Fe/Cr antiferromagnetic (AF) superlattice coupled with an m-layered Fe/Cr ferromagnetic (F) superlattice confirm the predicted collinear magnetization in the two superlattices. The two magnetized states of the F (along or opposite to the bias field) differ only in the relative orientation of the F and adjacent AF layer. The possibility of reading clearly the magnetic state at the interface pinpoints the commanding role that PNR is having in solving this intriguing problem

  16. Fixed points of occasionally weakly biased mappings

    OpenAIRE

    Y. Mahendra Singh, M. R. Singh

    2012-01-01

    Common fixed point results due to Pant et al. [Pant et al., Weak reciprocal continuity and fixed point theorems, Ann Univ Ferrara, 57(1), 181-190 (2011)] are extended to a class of non commuting operators called occasionally weakly biased pair[ N. Hussain, M. A. Khamsi A. Latif, Commonfixed points for JH-operators and occasionally weakly biased pairs under relaxed conditions, Nonlinear Analysis, 74, 2133-2140 (2011)]. We also provideillustrative examples to justify the improvements. Abstract....

  17. The Local Bias of Individual Investors

    OpenAIRE

    Ning Zhu

    2002-01-01

    This study investigates individual investors' bias towards nearby companies. Using data from a large U.S. discount brokerage, we find that individual investors tend to invest in companies closer to them relative to the market portfolio. Unlike Coval and Moskowitz's (1999) findings on institutional investors, however, we find that advantageous information cannot explain individual investors' local bias. Accounting numbers and information asymmetry matter less to individual investors' local bia...

  18. GENDER DIFFERENCES AND BIASES IN THE WORKPLACE

    OpenAIRE

    Shruti Srivastava*1 & Dr. Shweta S. Kulshrestha2

    2018-01-01

    Gender equality in the workplace has been a major concern for almost all the organizations and countries. Even in most developed countries we cannot find complete gender equality in true sense. This paper aims to discuss whether there is gender biasness in organizations or not? Gender biasness is considered as a major constraint towards the development process in any of the country and thus we have made an attempt to determine the root causes for gender gap that persists in our society. A...

  19. A new configurational bias scheme for sampling supramolecular structures

    Energy Technology Data Exchange (ETDEWEB)

    De Gernier, Robin; Mognetti, Bortolo M., E-mail: bmognett@ulb.ac.be [Center for Nonlinear Phenomena and Complex Systems, Université Libre de Bruxelles, Code Postal 231, Campus Plaine, B-1050 Brussels (Belgium); Curk, Tine [Department of Chemistry, University of Cambridge, Cambridge CB2 1EW (United Kingdom); Dubacheva, Galina V. [Biosurfaces Unit, CIC biomaGUNE, Paseo Miramon 182, 20009 Donostia - San Sebastian (Spain); Richter, Ralf P. [Biosurfaces Unit, CIC biomaGUNE, Paseo Miramon 182, 20009 Donostia - San Sebastian (Spain); Université Grenoble Alpes, DCM, 38000 Grenoble (France); CNRS, DCM, 38000 Grenoble (France); Max Planck Institute for Intelligent Systems, 70569 Stuttgart (Germany)

    2014-12-28

    We present a new simulation scheme which allows an efficient sampling of reconfigurable supramolecular structures made of polymeric constructs functionalized by reactive binding sites. The algorithm is based on the configurational bias scheme of Siepmann and Frenkel and is powered by the possibility of changing the topology of the supramolecular network by a non-local Monte Carlo algorithm. Such a plan is accomplished by a multi-scale modelling that merges coarse-grained simulations, describing the typical polymer conformations, with experimental results accounting for free energy terms involved in the reactions of the active sites. We test the new algorithm for a system of DNA coated colloids for which we compute the hybridisation free energy cost associated to the binding of tethered single stranded DNAs terminated by short sequences of complementary nucleotides. In order to demonstrate the versatility of our method, we also consider polymers functionalized by receptors that bind a surface decorated by ligands. In particular, we compute the density of states of adsorbed polymers as a function of the number of ligand–receptor complexes formed. Such a quantity can be used to study the conformational properties of adsorbed polymers useful when engineering adsorption with tailored properties. We successfully compare the results with the predictions of a mean field theory. We believe that the proposed method will be a useful tool to investigate supramolecular structures resulting from direct interactions between functionalized polymers for which efficient numerical methodologies of investigation are still lacking.

  20. Systematic biases in human heading estimation.

    Directory of Open Access Journals (Sweden)

    Luigi F Cuturi

    Full Text Available Heading estimation is vital to everyday navigation and locomotion. Despite extensive behavioral and physiological research on both visual and vestibular heading estimation over more than two decades, the accuracy of heading estimation has not yet been systematically evaluated. Therefore human visual and vestibular heading estimation was assessed in the horizontal plane using a motion platform and stereo visual display. Heading angle was overestimated during forward movements and underestimated during backward movements in response to both visual and vestibular stimuli, indicating an overall multimodal bias toward lateral directions. Lateral biases are consistent with the overrepresentation of lateral preferred directions observed in neural populations that carry visual and vestibular heading information, including MSTd and otolith afferent populations. Due to this overrepresentation, population vector decoding yields patterns of bias remarkably similar to those observed behaviorally. Lateral biases are inconsistent with standard bayesian accounts which predict that estimates should be biased toward the most common straight forward heading direction. Nevertheless, lateral biases may be functionally relevant. They effectively constitute a perceptual scale expansion around straight ahead which could allow for more precise estimation and provide a high gain feedback signal to facilitate maintenance of straight-forward heading during everyday navigation and locomotion.

  1. Domain wall engineering through exchange bias

    International Nuclear Information System (INIS)

    Albisetti, E.; Petti, D.

    2016-01-01

    The control of the structure and position of magnetic domain walls is at the basis of the development of different magnetic devices and architectures. Several nanofabrication techniques have been proposed to geometrically confine and shape domain wall structures; however, a fine tuning of the position and micromagnetic configuration is hardly achieved, especially in continuous films. This work shows that, by controlling the unidirectional anisotropy of a continuous ferromagnetic film through exchange bias, domain walls whose spin arrangement is generally not favored by dipolar and exchange interactions can be created. Micromagnetic simulations reveal that the domain wall width, position and profile can be tuned by establishing an abrupt change in the direction and magnitude of the exchange bias field set in the system. - Highlights: • Micromagnetic simulations study domain walls in exchange biased thin films. • Novel domain wall configurations can be stabilized via exchange bias. • Domain walls nucleate at the boundary of regions with different exchange bias. • Domain wall width and spin profile are controlled by tuning the exchange bias.

  2. The minor binding pocket: a major player in 7TM receptor activation

    DEFF Research Database (Denmark)

    Rosenkilde, Mette Marie; Benned-Jensen, Tau; Frimurer, Thomas M.

    2010-01-01

    residue located in one of two adjacent positions. Here we argue that this minor binding pocket is important for receptor activation. Functional coupling of the receptors seems to be mediated through the hydrogen bond network located between the intracellular segments of these TMs, with the allosteric...... targeted in the development of functionally biased drugs....

  3. Determination and Correction of Persistent Biases in Quantum Annealers

    Science.gov (United States)

    2016-08-25

    for all of the qubits. Narrowing of the bias distribution. To show the correctability of the persistent biases , we ran the experiment described above...this is a promising application for bias correction . Importantly, while the J biases determined here are in general smaller than the h biases , numerical...1Scientific RepoRts | 6:18628 | DOI: 10.1038/srep18628 www.nature.com/scientificreports Determination and correction of persistent biases in quantum

  4. Evolution of endothelin receptors in vertebrates.

    Science.gov (United States)

    Braasch, Ingo; Schartl, Manfred

    2014-12-01

    Endothelin receptors are G protein coupled receptors (GPCRs) of the β-group of rhodopsin receptors that bind to endothelin ligands, which are 21 amino acid long peptides derived from longer prepro-endothelin precursors. The most basal Ednr-like GPCR is found outside vertebrates in the cephalochordate amphioxus, but endothelin ligands are only present among vertebrates, including the lineages of jawless vertebrates (lampreys and hagfishes), cartilaginous vertebrates (sharks, rays, and chimaeras), and bony vertebrates (ray-finned fishes and lobe-finned vertebrates including tetrapods). A bona fide endothelin system is thus a vertebrate-specific innovation with important roles for regulating the cardiovascular system, renal and pulmonary processes, as well as for the development of the vertebrate-specific neural crest cell population and its derivatives. Expectedly, dysregulation of endothelin receptors and the endothelin system leads to a multitude of human diseases. Despite the importance of different types of endothelin receptors for vertebrate development and physiology, current knowledge on endothelin ligand-receptor interactions, on the expression of endothelin receptors and their ligands, and on the functional roles of the endothelin system for embryonic development and in adult vertebrates is very much biased towards amniote vertebrates. Recent analyses from a variety of vertebrate lineages, however, have shown that the endothelin system in lineages such as teleost fish and lampreys is more diverse and is divergent from the mammalian endothelin system. This diversity is mainly based on differential evolution of numerous endothelin system components among vertebrate lineages generated by two rounds of whole genome duplication (three in teleosts) during vertebrate evolution. Here we review current understanding of the evolutionary history of the endothelin receptor family in vertebrates supplemented with surveys on the endothelin receptor gene complement of

  5. The LDL receptor.

    Science.gov (United States)

    Goldstein, Joseph L; Brown, Michael S

    2009-04-01

    In this article, the history of the LDL receptor is recounted by its codiscoverers. Their early work on the LDL receptor explained a genetic cause of heart attacks and led to new ways of thinking about cholesterol metabolism. The LDL receptor discovery also introduced three general concepts to cell biology: receptor-mediated endocytosis, receptor recycling, and feedback regulation of receptors. The latter concept provides the mechanism by which statins selectively lower plasma LDL, reducing heart attacks and prolonging life.

  6. Beyond assembly bias: exploring secondary halo biases for cluster-size haloes

    Science.gov (United States)

    Mao, Yao-Yuan; Zentner, Andrew R.; Wechsler, Risa H.

    2018-03-01

    Secondary halo bias, commonly known as `assembly bias', is the dependence of halo clustering on a halo property other than mass. This prediction of the Λ Cold Dark Matter cosmology is essential to modelling the galaxy distribution to high precision and interpreting clustering measurements. As the name suggests, different manifestations of secondary halo bias have been thought to originate from halo assembly histories. We show conclusively that this is incorrect for cluster-size haloes. We present an up-to-date summary of secondary halo biases of high-mass haloes due to various halo properties including concentration, spin, several proxies of assembly history, and subhalo properties. While concentration, spin, and the abundance and radial distribution of subhaloes exhibit significant secondary biases, properties that directly quantify halo assembly history do not. In fact, the entire assembly histories of haloes in pairs are nearly identical to those of isolated haloes. In general, a global correlation between two halo properties does not predict whether or not these two properties exhibit similar secondary biases. For example, assembly history and concentration (or subhalo abundance) are correlated for both paired and isolated haloes, but follow slightly different conditional distributions in these two cases. This results in a secondary halo bias due to concentration (or subhalo abundance), despite the lack of assembly bias in the strict sense for cluster-size haloes. Due to this complexity, caution must be exercised in using any one halo property as a proxy to study the secondary bias due to another property.

  7. Affective Biases in Humans and Animals.

    Science.gov (United States)

    Robinson, E S J; Roiser, J P

    Depression is one of the most common but poorly understood psychiatric conditions. Although drug treatments and psychological therapies are effective in some patients, many do not achieve full remission and some patients receive no apparent benefit. Developing new improved treatments requires a better understanding of the aetiology of symptoms and evaluation of novel therapeutic targets in pre-clinical studies. Recent developments in our understanding of the basic cognitive processes that may contribute to the development of depression and its treatment offer new opportunities for both clinical and pre-clinical research. This chapter discusses the clinical evidence supporting a cognitive neuropsychological model of depression and antidepressant efficacy, and how this information may be usefully translated to pre-clinical investigation. Studies using neuropsychological tests in depressed patients and at risk populations have revealed basic negative emotional biases and disrupted reward and punishment processing, which may also impact on non-affective cognition. These affective biases are sensitive to antidepressant treatments with early onset effects observed, suggesting an important role in recovery. This clinical work into affective biases has also facilitated back-translation to animals and the development of assays to study affective biases in rodents. These animal studies suggest that, similar to humans, rodents in putative negative affective states exhibit negative affective biases on decision-making and memory tasks. Antidepressant treatments also induce positive biases in these rodent tasks, supporting the translational validity of this approach. Although still in the early stages of development and validation, affective biases in depression have the potential to offer new insights into the clinical condition, as well as facilitating the development of more translational approaches for pre-clinical studies.

  8. On the relative independence of thinking biases and cognitive ability.

    Science.gov (United States)

    Stanovich, Keith E; West, Richard F

    2008-04-01

    In 7 different studies, the authors observed that a large number of thinking biases are uncorrelated with cognitive ability. These thinking biases include some of the most classic and well-studied biases in the heuristics and biases literature, including the conjunction effect, framing effects, anchoring effects, outcome bias, base-rate neglect, "less is more" effects, affect biases, omission bias, myside bias, sunk-cost effect, and certainty effects that violate the axioms of expected utility theory. In a further experiment, the authors nonetheless showed that cognitive ability does correlate with the tendency to avoid some rational thinking biases, specifically the tendency to display denominator neglect, probability matching rather than maximizing, belief bias, and matching bias on the 4-card selection task. The authors present a framework for predicting when cognitive ability will and will not correlate with a rational thinking tendency. (c) 2008 APA, all rights reserved.

  9. Non-Gaussian halo assembly bias

    International Nuclear Information System (INIS)

    Reid, Beth A.; Verde, Licia; Dolag, Klaus; Matarrese, Sabino; Moscardini, Lauro

    2010-01-01

    The strong dependence of the large-scale dark matter halo bias on the (local) non-Gaussianity parameter, f NL , offers a promising avenue towards constraining primordial non-Gaussianity with large-scale structure surveys. In this paper, we present the first detection of the dependence of the non-Gaussian halo bias on halo formation history using N-body simulations. We also present an analytic derivation of the expected signal based on the extended Press-Schechter formalism. In excellent agreement with our analytic prediction, we find that the halo formation history-dependent contribution to the non-Gaussian halo bias (which we call non-Gaussian halo assembly bias) can be factorized in a form approximately independent of redshift and halo mass. The correction to the non-Gaussian halo bias due to the halo formation history can be as large as 100%, with a suppression of the signal for recently formed halos and enhancement for old halos. This could in principle be a problem for realistic galaxy surveys if observational selection effects were to pick galaxies occupying only recently formed halos. Current semi-analytic galaxy formation models, for example, imply an enhancement in the expected signal of ∼ 23% and ∼ 48% for galaxies at z = 1 selected by stellar mass and star formation rate, respectively

  10. Differential structural properties of GLP-1 and exendin-4 determine their relative affinity for the GLP-1 receptor N-terminal extracellular domain.

    Science.gov (United States)

    Runge, Steffen; Schimmer, Susann; Oschmann, Jan; Schiødt, Christine Bruun; Knudsen, Sanne Möller; Jeppesen, Claus Bekker; Madsen, Kjeld; Lau, Jesper; Thøgersen, Henning; Rudolph, Rainer

    2007-05-15

    Glucagon-like peptide-1 (GLP-1) and exendin-4 (Ex4) are homologous peptides with established potential for treatment of type 2 diabetes. They bind and activate the pancreatic GLP-1 receptor (GLP-1R) with similar affinity and potency and thereby promote insulin secretion in a glucose-dependent manner. GLP-1R belongs to family B of the seven transmembrane G-protein coupled receptors. The N-terminal extracellular domain (nGLP-1R) is a ligand binding domain with differential affinity for Ex4 and GLP-1: low affinity for GLP-1 and high affinity for exendin-4. The superior affinity of nGLP-1R for Ex4 was previously explained by an additional interaction between nGLP-1R and the C-terminal Trp-cage of Ex4. In this study we have combined biophysical and pharmacological approaches thus relating structural properties of the ligands in solution to their relative binding affinity for nGLP-1R. We used both a tracer competition assay and ligand-induced thermal stabilization of nGLP-1R to measure the relative affinity of full length, truncated, and chimeric ligands for soluble refolded nGLP-1R. The ligands in solution and the conformational consequences of ligand binding to nGLP-1R were characterized by circular dichroism and fluorescence spectroscopy. We found a correlation between the helical content of the free ligands and their relative binding affinity for nGLP-1R, supporting the hypothesis that the ligands are helical at least in the segment that binds to nGLP-1R. The Trp-cage of Ex4 was not necessary to maintain a superior helicity of Ex4 compared to GLP-1. The results suggest that the differential affinity of nGLP-1R is explained almost entirely by divergent residues in the central part of the ligands: Leu10-Gly30 of Ex4 and Val16-Arg36 of GLP-1. In view of our results it appears that the Trp-cage plays only a minor role for the interaction between Ex4 and nGLP-1R and for the differential affinity of nGLP-1R for GLP-1 and Ex4.

  11. Hindsight bias and outcome bias in the social construction of medical negligence: a review.

    Science.gov (United States)

    Hugh, Thomas B; Dekker, Sidney W A

    2009-05-01

    Medical negligence has been the subject of much public debate in recent decades. Although the steep increase in the frequency and size of claims against doctors at the end of the last century appears to have plateaued, in Australia at least, medical indemnity costs and consequences are still a matter of concern for doctors, medical defence organisations and governments in most developed countries. Imprecision in the legal definition of negligence opens the possibility that judgments of this issue at several levels may be subject to hindsight and outcome bias. Hindsight bias relates to the probability of an adverse event perceived by a retrospective observer ("I would have known it was going to happen"), while outcome bias is a largely subconscious cognitive distortion produced by the observer's knowledge of the adverse outcome. This review examines the relevant legal, medical, psychological and sociological literature on the operation of these pervasive and universal biases in the retrospective evaluation of adverse events. A finding of medical negligence is essentially an after-the-event social construction and is invariably affected by hindsight bias and knowledge of the adverse outcome. Such biases obviously pose a threat to the fairness of judgments. A number of debiasing strategies have been suggested but are relatively ineffective because of the universality and strength of these biases and the inherent difficulty of concealing from expert witnesses knowledge of the outcome. Education about the effect of the biases is therefore important for lawyers, medical expert witnesses and the judiciary.

  12. Attention bias modification training under working memory load increases the magnitude of change in attentional bias.

    Science.gov (United States)

    Clarke, Patrick J F; Branson, Sonya; Chen, Nigel T M; Van Bockstaele, Bram; Salemink, Elske; MacLeod, Colin; Notebaert, Lies

    2017-12-01

    Attention bias modification (ABM) procedures have shown promise as a therapeutic intervention, however current ABM procedures have proven inconsistent in their ability to reliably achieve the requisite change in attentional bias needed to produce emotional benefits. This highlights the need to better understand the precise task conditions that facilitate the intended change in attention bias in order to realise the therapeutic potential of ABM procedures. Based on the observation that change in attentional bias occurs largely outside conscious awareness, the aim of the current study was to determine if an ABM procedure delivered under conditions likely to preclude explicit awareness of the experimental contingency, via the addition of a working memory load, would contribute to greater change in attentional bias. Bias change was assessed among 122 participants in response to one of four ABM tasks given by the two experimental factors of ABM training procedure delivered either with or without working memory load, and training direction of either attend-negative or avoid-negative. Findings revealed that avoid-negative ABM procedure under working memory load resulted in significantly greater reductions in attentional bias compared to the equivalent no-load condition. The current findings will require replication with clinical samples to determine the utility of the current task for achieving emotional benefits. These present findings are consistent with the position that the addition of a working memory load may facilitate change in attentional bias in response to an ABM training procedure. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Research bias in judgement bias studies : a systematic review of valuation judgement literature

    NARCIS (Netherlands)

    Vincent Gruis; Pim Klamer; Cok Bakker

    2017-01-01

    Valuation judgement bias has been a research topic for several years due to its proclaimed effect on valuation accuracy. However, little is known on the emphasis of literature on judgement bias, with regard to, for instance, research methodologies, research context and robustness of research

  14. Research bias in judgement bias studies : A systematic review of valuation judgement literature

    NARCIS (Netherlands)

    Klamer, Pim; Bakker, C.; Gruis, Vincent

    2017-01-01

    Valuation judgement bias has been a research topic for several years due to its proclaimed effect on valuation accuracy. However, little is known on the emphasis of literature on judgement bias, with regard to, for instance, research methodologies, research context and robustness of research

  15. Placebo effect studies are susceptible to response bias and to other types of biases

    DEFF Research Database (Denmark)

    Hróbjartsson, Asbjørn; Kaptchuk, Ted J; Miller, Franklin G

    2011-01-01

    Investigations of the effect of placebo are often challenging to conduct and interpret. The history of placebo shows that assessment of its clinical significance has a real potential to be biased. We analyze and discuss typical types of bias in studies on placebo....

  16. Toward a synthesis of cognitive biases: how noisy information processing can bias human decision making.

    Science.gov (United States)

    Hilbert, Martin

    2012-03-01

    A single coherent framework is proposed to synthesize long-standing research on 8 seemingly unrelated cognitive decision-making biases. During the past 6 decades, hundreds of empirical studies have resulted in a variety of rules of thumb that specify how humans systematically deviate from what is normatively expected from their decisions. Several complementary generative mechanisms have been proposed to explain those cognitive biases. Here it is suggested that (at least) 8 of these empirically detected decision-making biases can be produced by simply assuming noisy deviations in the memory-based information processes that convert objective evidence (observations) into subjective estimates (decisions). An integrative framework is presented to show how similar noise-based mechanisms can lead to conservatism, the Bayesian likelihood bias, illusory correlations, biased self-other placement, subadditivity, exaggerated expectation, the confidence bias, and the hard-easy effect. Analytical tools from information theory are used to explore the nature and limitations that characterize such information processes for binary and multiary decision-making exercises. The ensuing synthesis offers formal mathematical definitions of the biases and their underlying generative mechanism, which permits a consolidated analysis of how they are related. This synthesis contributes to the larger goal of creating a coherent picture that explains the relations among the myriad of seemingly unrelated biases and their potential psychological generative mechanisms. Limitations and research questions are discussed.

  17. A Comparison of attentional biases and memory biases in social phobia and major depression

    NARCIS (Netherlands)

    Rinck, M.; Becker, E.S.

    2005-01-01

    Cognitive processes play an important role in the etiology and maintenance of anxiety and depression. Current theories differ, however, in their predictions regarding the occurrence of attentional biases and memory biases in depression and anxiety. To allow for a systematic comparison of disorders

  18. Recognition bias and the physical attractiveness stereotype.

    Science.gov (United States)

    Rohner, Jean-Christophe; Rasmussen, Anders

    2012-06-01

    Previous studies have found a recognition bias for information consistent with the physical attractiveness stereotype (PAS), in which participants believe that they remember that attractive individuals have positive qualities and that unattractive individuals have negative qualities, regardless of what information actually occurred. The purpose of this research was to examine whether recognition bias for PAS congruent information is replicable and invariant across a variety of conditions (i.e. generalizable). The effects of nine different moderator variables were examined in two experiments. With a few exceptions, the effect of PAS congruence on recognition bias was independent of the moderator variables. The results suggest that the tendency to believe that one remembers information consistent with the physical attractiveness stereotype is a robust phenomenon. © 2012 The Authors. Scandinavian Journal of Psychology © 2012 The Scandinavian Psychological Associations.

  19. Systematic approach to establishing criticality biases

    International Nuclear Information System (INIS)

    Larson, S.L.

    1995-09-01

    A systematic approach has been developed to determine benchmark biases and apply those biases to code results to meet the requirements of DOE Order 5480.24 regarding documenting criticality safety margins. Previously, validation of the code against experimental benchmarks to prove reasonable agreement was sufficient. However, DOE Order 5480.24 requires contractors to adhere to the requirements of ANSI/ANS-8.1 and establish subcritical margins. A method was developed to incorporate biases and uncertainties from benchmark calculations into a k eff value with quantifiable uncertainty. The method produces a 95% confidence level in both the k eff value of the scenario modeled and the distribution of the k eff S calculated by the Monte Carlo code. Application of the method to a group of benchmarks modeled using the KENO-Va code and the SCALE 27 group cross sections is also presented

  20. Optimism Bias in Fans and Sports Reporters.

    Science.gov (United States)

    Love, Bradley C; Kopeć, Łukasz; Guest, Olivia

    2015-01-01

    People are optimistic about their prospects relative to others. However, existing studies can be difficult to interpret because outcomes are not zero-sum. For example, one person avoiding cancer does not necessitate that another person develops cancer. Ideally, optimism bias would be evaluated within a closed formal system to establish with certainty the extent of the bias and the associated environmental factors, such that optimism bias is demonstrated when a population is internally inconsistent. Accordingly, we asked NFL fans to predict how many games teams they liked and disliked would win in the 2015 season. Fans, like ESPN reporters assigned to cover a team, were overly optimistic about their team's prospects. The opposite pattern was found for teams that fans disliked. Optimism may flourish because year-to-year team results are marked by auto-correlation and regression to the group mean (i.e., good teams stay good, but bad teams improve).

  1. Optimism Bias in Fans and Sports Reporters

    Science.gov (United States)

    Love, Bradley C.

    2015-01-01

    People are optimistic about their prospects relative to others. However, existing studies can be difficult to interpret because outcomes are not zero-sum. For example, one person avoiding cancer does not necessitate that another person develops cancer. Ideally, optimism bias would be evaluated within a closed formal system to establish with certainty the extent of the bias and the associated environmental factors, such that optimism bias is demonstrated when a population is internally inconsistent. Accordingly, we asked NFL fans to predict how many games teams they liked and disliked would win in the 2015 season. Fans, like ESPN reporters assigned to cover a team, were overly optimistic about their team’s prospects. The opposite pattern was found for teams that fans disliked. Optimism may flourish because year-to-year team results are marked by auto-correlation and regression to the group mean (i.e., good teams stay good, but bad teams improve). PMID:26352146

  2. Motion, identity and the bias toward agency

    Directory of Open Access Journals (Sweden)

    Chris eFields

    2014-08-01

    Full Text Available The well-documented human bias toward agency as a cause and therefore an explanation of observed events is typically attributed to evolutionary selection for a social brain. Based on a review of developmental and adult behavioral and neurocognitive data, it is argued that the bias toward agency is a result of the default human solution, developed during infancy, to the computational requirements of object re-identification over gaps in observation of more than a few seconds. If this model is correct, overriding the bias toward agency to construct mechanistic explanations of observed events requires structure-mapping inferences, implemented by the pre-motor action planning system, that replace agents with mechanisms as causes of unobserved changes in contextual or featural properties of objects. Experiments that would test this model are discussed.

  3. Skill-Biased Technological Change in Denmark

    DEFF Research Database (Denmark)

    Malchow-Møller, Nikolaj; Rose Skaksen, Jan

    2003-01-01

    Skill-Biased Technological Change in Denmark:A Disaggregate Perspective@*In this paper, we provide an industry-level analysis of skill-biased technological change(SBTC) in Denmark over the last two decades. The analysis shows that SBTC has variedconsiderably across industries, and traditionally...... large Danish industries have experiencedrelatively less SBTC. This may partly explain why wage inequality between skilled and lessskilled has risen less in Denmark than in other countries. We also find that SBTC has beenconcentrated in already skill-intensive industries. This contains important...... information aboutfuture labour requirements, as the relative importance of these industries must be expectedto grow, thereby reinforcing the shift in demand for skilled labour.JEL Classification: J24, J31, L6Keywords: skill-biased technological change, Danish industries...

  4. A system for biasing a differential amplifier

    International Nuclear Information System (INIS)

    Barbier, Daniel; Ittel, J.M.; Poujois, Robert

    1975-01-01

    This invention concerns a system for biasing a differential amplifier. It particularly applies to the integrated differential amplifiers designed with MOS field effect transistors. Variations in the technological parameters may well cause the amplifying transistors to work outside their usual operational area, in other words outside the linear part of the transfer characteristic. To ensure that these transistors function correctly, it is necessary that the value of the voltage difference at the output be equally null. To do this and to centre on the so called 'rest' point of the amplifier transfer charateristic, the condition will be set that the output potentials of each amplifier transistor should have a zero value or a constant value as sum. With this in view, the bias on the source (generally a transistor powered by its grid bias voltage) supplying current to the two amplifying transistors fitted in parallel, is permanently adjusted in a suitable manner [fr

  5. Using Machine Learning to Predict MCNP Bias

    Energy Technology Data Exchange (ETDEWEB)

    Grechanuk, Pavel Aleksandrovi [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2018-01-09

    For many real-world applications in radiation transport where simulations are compared to experimental measurements, like in nuclear criticality safety, the bias (simulated - experimental keff) in the calculation is an extremely important quantity used for code validation. The objective of this project is to accurately predict the bias of MCNP6 [1] criticality calculations using machine learning (ML) algorithms, with the intention of creating a tool that can complement the current nuclear criticality safety methods. In the latest release of MCNP6, the Whisper tool is available for criticality safety analysts and includes a large catalogue of experimental benchmarks, sensitivity profiles, and nuclear data covariance matrices. This data, coming from 1100+ benchmark cases, is used in this study of ML algorithms for criticality safety bias predictions.

  6. NCBI nr-aa BLAST: CBRC-TBEL-01-1998 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-TBEL-01-1998 sp|Q8NH41|OR4KF_HUMAN Olfactory receptor 4K15 dbj|BAC05798.1| sev...en transmembrane helix receptor [Homo sapiens] gb|EAW66492.1| olfactory receptor, family 4, subfamily K, member 15 [Homo sapiens] Q8NH41 1e-82 95% ...

  7. NCBI nr-aa BLAST: CBRC-PTRO-19-0002 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-PTRO-19-0002 sp|Q8NH41|OR4KF_HUMAN Olfactory receptor 4K15 dbj|BAC05798.1| sev...en transmembrane helix receptor [Homo sapiens] gb|EAW66492.1| olfactory receptor, family 4, subfamily K, member 15 [Homo sapiens] Q8NH41 1e-163 93% ...

  8. NCBI nr-aa BLAST: CBRC-PABE-26-0241 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-PABE-26-0241 sp|Q8NH41|OR4KF_HUMAN Olfactory receptor 4K15 dbj|BAC05798.1| sev...en transmembrane helix receptor [Homo sapiens] gb|EAW66492.1| olfactory receptor, family 4, subfamily K, member 15 [Homo sapiens] Q8NH41 1e-120 66% ...

  9. NCBI nr-aa BLAST: CBRC-CFAM-08-0013 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-CFAM-08-0013 sp|Q8NH41|OR4KF_HUMAN Olfactory receptor 4K15 dbj|BAC05798.1| sev...en transmembrane helix receptor [Homo sapiens] gb|EAW66492.1| olfactory receptor, family 4, subfamily K, member 15 [Homo sapiens] Q8NH41 3e-93 57% ...

  10. NCBI nr-aa BLAST: CBRC-EEUR-01-0561 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-EEUR-01-0561 sp|Q8NH41|OR4KF_HUMAN Olfactory receptor 4K15 dbj|BAC05798.1| sev...en transmembrane helix receptor [Homo sapiens] gb|EAW66492.1| olfactory receptor, family 4, subfamily K, member 15 [Homo sapiens] Q8NH41 1e-160 88% ...

  11. NCBI nr-aa BLAST: CBRC-HSAP-21-0002 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-HSAP-21-0002 sp|Q8NH41|OR4KF_HUMAN Olfactory receptor 4K15 dbj|BAC05798.1| sev...en transmembrane helix receptor [Homo sapiens] gb|EAW66492.1| olfactory receptor, family 4, subfamily K, member 15 [Homo sapiens] Q8NH41 1e-165 94% ...

  12. NCBI nr-aa BLAST: CBRC-BTAU-01-0320 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-BTAU-01-0320 sp|Q8NH41|OR4KF_HUMAN Olfactory receptor 4K15 dbj|BAC05798.1| sev...en transmembrane helix receptor [Homo sapiens] gb|EAW66492.1| olfactory receptor, family 4, subfamily K, member 15 [Homo sapiens] Q8NH41 1e-159 88% ...

  13. NCBI nr-aa BLAST: CBRC-HSAP-18-0009 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-HSAP-18-0009 sp|Q8NH41|OR4KF_HUMAN Olfactory receptor 4K15 dbj|BAC05798.1| sev...en transmembrane helix receptor [Homo sapiens] gb|EAW66492.1| olfactory receptor, family 4, subfamily K, member 15 [Homo sapiens] Q8NH41 1e-154 90% ...

  14. NCBI nr-aa BLAST: CBRC-OANA-01-0544 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-OANA-01-0544 sp|Q8NH41|OR4KF_HUMAN Olfactory receptor 4K15 dbj|BAC05798.1| sev...en transmembrane helix receptor [Homo sapiens] gb|EAW66492.1| olfactory receptor, family 4, subfamily K, member 15 [Homo sapiens] Q8NH41 1e-124 71% ...

  15. NCBI nr-aa BLAST: CBRC-DNOV-01-0496 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-DNOV-01-0496 sp|Q8NH41|OR4KF_HUMAN Olfactory receptor 4K15 dbj|BAC05798.1| sev...en transmembrane helix receptor [Homo sapiens] gb|EAW66492.1| olfactory receptor, family 4, subfamily K, member 15 [Homo sapiens] Q8NH41 1e-148 82% ...

  16. NCBI nr-aa BLAST: CBRC-DNOV-01-1358 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-DNOV-01-1358 sp|Q8NH41|OR4KF_HUMAN Olfactory receptor 4K15 dbj|BAC05798.1| sev...en transmembrane helix receptor [Homo sapiens] gb|EAW66492.1| olfactory receptor, family 4, subfamily K, member 15 [Homo sapiens] Q8NH41 1e-127 77% ...

  17. NCBI nr-aa BLAST: CBRC-BTAU-01-1781 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-BTAU-01-1781 sp|Q8NH41|OR4KF_HUMAN Olfactory receptor 4K15 dbj|BAC05798.1| sev...en transmembrane helix receptor [Homo sapiens] gb|EAW66492.1| olfactory receptor, family 4, subfamily K, member 15 [Homo sapiens] Q8NH41 1e-120 67% ...

  18. NCBI nr-aa BLAST: CBRC-SARA-01-0472 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-SARA-01-0472 sp|Q8NH41|OR4KF_HUMAN Olfactory receptor 4K15 dbj|BAC05798.1| sev...en transmembrane helix receptor [Homo sapiens] gb|EAW66492.1| olfactory receptor, family 4, subfamily K, member 15 [Homo sapiens] Q8NH41 1e-164 89% ...

  19. NCBI nr-aa BLAST: CBRC-DNOV-01-0029 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-DNOV-01-0029 sp|Q8NH41|OR4KF_HUMAN Olfactory receptor 4K15 dbj|BAC05798.1| sev...en transmembrane helix receptor [Homo sapiens] gb|EAW66492.1| olfactory receptor, family 4, subfamily K, member 15 [Homo sapiens] Q8NH41 4e-99 83% ...

  20. NCBI nr-aa BLAST: CBRC-OGAR-01-0926 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-OGAR-01-0926 sp|Q8NH41|OR4KF_HUMAN Olfactory receptor 4K15 dbj|BAC05798.1| sev...en transmembrane helix receptor [Homo sapiens] gb|EAW66492.1| olfactory receptor, family 4, subfamily K, member 15 [Homo sapiens] Q8NH41 1e-150 79% ...

  1. NCBI nr-aa BLAST: CBRC-DNOV-01-2040 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-DNOV-01-2040 sp|Q8NH41|OR4KF_HUMAN Olfactory receptor 4K15 dbj|BAC05798.1| sev...en transmembrane helix receptor [Homo sapiens] gb|EAW66492.1| olfactory receptor, family 4, subfamily K, member 15 [Homo sapiens] Q8NH41 5e-74 62% ...

  2. NCBI nr-aa BLAST: CBRC-HSAP-14-0016 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-HSAP-14-0016 sp|Q8NH41|OR4KF_HUMAN Olfactory receptor 4K15 dbj|BAC05798.1| sev...en transmembrane helix receptor [Homo sapiens] gb|EAW66492.1| olfactory receptor, family 4, subfamily K, member 15 [Homo sapiens] Q8NH41 1e-179 100% ...

  3. NCBI nr-aa BLAST: CBRC-LAFR-01-1318 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-LAFR-01-1318 sp|Q8NH41|OR4KF_HUMAN Olfactory receptor 4K15 dbj|BAC05798.1| sev...en transmembrane helix receptor [Homo sapiens] gb|EAW66492.1| olfactory receptor, family 4, subfamily K, member 15 [Homo sapiens] Q8NH41 1e-120 68% ...

  4. NCBI nr-aa BLAST: CBRC-PABE-15-0006 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-PABE-15-0006 sp|Q8NH41|OR4KF_HUMAN Olfactory receptor 4K15 dbj|BAC05798.1| sev...en transmembrane helix receptor [Homo sapiens] gb|EAW66492.1| olfactory receptor, family 4, subfamily K, member 15 [Homo sapiens] Q8NH41 1e-173 96% ...

  5. NCBI nr-aa BLAST: CBRC-LAFR-01-0314 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-LAFR-01-0314 sp|Q8NH41|OR4KF_HUMAN Olfactory receptor 4K15 dbj|BAC05798.1| sev...en transmembrane helix receptor [Homo sapiens] gb|EAW66492.1| olfactory receptor, family 4, subfamily K, member 15 [Homo sapiens] Q8NH41 1e-164 90% ...

  6. NCBI nr-aa BLAST: CBRC-RMAC-07-0037 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-RMAC-07-0037 sp|Q8NH41|OR4KF_HUMAN Olfactory receptor 4K15 dbj|BAC05798.1| sev...en transmembrane helix receptor [Homo sapiens] gb|EAW66492.1| olfactory receptor, family 4, subfamily K, member 15 [Homo sapiens] Q8NH41 1e-171 97% ...

  7. NCBI nr-aa BLAST: CBRC-DNOV-01-1298 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-DNOV-01-1298 sp|Q8NH41|OR4KF_HUMAN Olfactory receptor 4K15 dbj|BAC05798.1| sev...en transmembrane helix receptor [Homo sapiens] gb|EAW66492.1| olfactory receptor, family 4, subfamily K, member 15 [Homo sapiens] Q8NH41 2e-77 66% ...

  8. NCBI nr-aa BLAST: CBRC-OCUN-01-0611 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-OCUN-01-0611 sp|Q8NH41|OR4KF_HUMAN Olfactory receptor 4K15 dbj|BAC05798.1| sev...en transmembrane helix receptor [Homo sapiens] gb|EAW66492.1| olfactory receptor, family 4, subfamily K, member 15 [Homo sapiens] Q8NH41 1e-160 87% ...

  9. NCBI nr-aa BLAST: CBRC-DNOV-01-1757 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-DNOV-01-1757 sp|Q8NH41|OR4KF_HUMAN Olfactory receptor 4K15 dbj|BAC05798.1| sev...en transmembrane helix receptor [Homo sapiens] gb|EAW66492.1| olfactory receptor, family 4, subfamily K, member 15 [Homo sapiens] Q8NH41 1e-167 90% ...

  10. NCBI nr-aa BLAST: CBRC-SARA-01-1206 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-SARA-01-1206 sp|Q8NH41|OR4KF_HUMAN Olfactory receptor 4K15 dbj|BAC05798.1| sev...en transmembrane helix receptor [Homo sapiens] gb|EAW66492.1| olfactory receptor, family 4, subfamily K, member 15 [Homo sapiens] Q8NH41 1e-40 85% ...

  11. NCBI nr-aa BLAST: CBRC-DNOV-01-0070 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-DNOV-01-0070 sp|Q8NH41|OR4KF_HUMAN Olfactory receptor 4K15 dbj|BAC05798.1| sev...en transmembrane helix receptor [Homo sapiens] gb|EAW66492.1| olfactory receptor, family 4, subfamily K, member 15 [Homo sapiens] Q8NH41 2e-81 71% ...

  12. NCBI nr-aa BLAST: CBRC-BTAU-01-0090 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-BTAU-01-0090 sp|Q8NH41|OR4KF_HUMAN Olfactory receptor 4K15 dbj|BAC05798.1| sev...en transmembrane helix receptor [Homo sapiens] gb|EAW66492.1| olfactory receptor, family 4, subfamily K, member 15 [Homo sapiens] Q8NH41 1e-162 90% ...

  13. Beyond attentional bias: a perceptual bias in a dot-probe task.

    Science.gov (United States)

    Bocanegra, Bruno R; Huijding, Jorg; Zeelenberg, René

    2012-12-01

    Previous dot-probe studies indicate that threat-related face cues induce a bias in spatial attention. Independently of spatial attention, a recent psychophysical study suggests that a bilateral fearful face cue improves low spatial-frequency perception (LSF) and impairs high spatial-frequency perception (HSF). Here, we combine these separate lines of research within a single dot-probe paradigm. We found that a bilateral fearful face cue, compared with a bilateral neutral face cue, speeded up responses to LSF targets and slowed down responses to HSF targets. This finding is important, as it shows that emotional cues in dot-probe tasks not only bias where information is preferentially processed (i.e., an attentional bias in spatial location), but also bias what type of information is preferentially processed (i.e., a perceptual bias in spatial frequency). PsycINFO Database Record (c) 2012 APA, all rights reserved.

  14. Biasing of Capacitive Micromachined Ultrasonic Transducers.

    Science.gov (United States)

    Caliano, Giosue; Matrone, Giulia; Savoia, Alessandro Stuart

    2017-02-01

    Capacitive micromachined ultrasonic transducers (CMUTs) represent an effective alternative to piezoelectric transducers for medical ultrasound imaging applications. They are microelectromechanical devices fabricated using silicon micromachining techniques, developed in the last two decades in many laboratories. The interest for this novel transducer technology relies on its full compatibility with standard integrated circuit technology that makes it possible to integrate on the same chip the transducers and the electronics, thus enabling the realization of extremely low-cost and high-performance devices, including both 1-D or 2-D arrays. Being capacitive transducers, CMUTs require a high bias voltage to be properly operated in pulse-echo imaging applications. The typical bias supply residual ripple of high-quality high-voltage (HV) generators is in the millivolt range, which is comparable with the amplitude of the received echo signals, and it is particularly difficult to minimize. The aim of this paper is to analyze the classical CMUT biasing circuits, highlighting the features of each one, and to propose two novel HV generator architectures optimized for CMUT biasing applications. The first circuit proposed is an ultralow-residual ripple (generator that uses an extremely stable sinusoidal power oscillator topology. The second circuit employs a commercially available integrated step-up converter characterized by a particularly efficient switching topology. The circuit is used to bias the CMUT by charging a buffer capacitor synchronously with the pulsing sequence, thus reducing the impact of the switching noise on the received echo signals. The small area of the circuit (about 1.5 cm 2 ) makes it possible to generate the bias voltage inside the probe, very close to the CMUT, making the proposed solution attractive for portable applications. Measurements and experiments are shown to demonstrate the effectiveness of the new approaches presented.

  15. Best Practices in Hiring: Addressing Unconscious Bias

    Science.gov (United States)

    Simpson, Caroline E.

    2012-01-01

    Research has shown that implementing certain hiring practices will increase diversity in the workplace while enhancing academic quality. All of these practices rely on addressing the issue of 'unconscious bias.' A brief overview of unconscious bias--what it is, how it works, and simple measures to counter it--will be presented. Successful strategies, actions, and recommendations for implementing best recruiting and hiring practices, which have been proven to enhance academic excellence by ensuring a deep and diverse applicant pool, will also be presented.

  16. Reducing hypothetical bias in choice experiments

    DEFF Research Database (Denmark)

    Ladenburg, Jacob; Olsen, Søren Bøye; Nielsen, Rasmus Christian Fejer

    eliminate some of the hypothetical bias. The present paper tests an addition to Cheap Talk, an Opt-Out Reminder. The Opt-Out Reminder is an objective short script presented prior to the choice sets, prompting the respondent to choose the opt-out alternative, if he/she finds the proposed policy generated...... alternatives in a choice set too expensive. The results suggest that adding an Opt-Out Reminder to Cheap Talk can in fact reduce hypothetical bias even further and reduces some of the ineffectiveness of CT in relation to the survey bid range and experienced respondents....

  17. Accounting for discovery bias in genomic prediction

    Science.gov (United States)

    Our objective was to evaluate an approach to mitigating discovery bias in genomic prediction. Accuracy may be improved by placing greater emphasis on regions of the genome expected to be more influential on a trait. Methods emphasizing regions result in a phenomenon known as “discovery bias” if info...

  18. Group rationale, collective sense : Beyond intergroup bias

    NARCIS (Netherlands)

    Spears, Russell

    In this paper, I contest the view of the group as a source of bias and irrationality, especially prevalent within social psychology. I argue that this negative evaluation often arises by applying inappropriate standards, relating to the wrong level of analysis (often the individual level). Second,

  19. Biased Monte Carlo optimization: the basic approach

    International Nuclear Information System (INIS)

    Campioni, Luca; Scardovelli, Ruben; Vestrucci, Paolo

    2005-01-01

    It is well-known that the Monte Carlo method is very successful in tackling several kinds of system simulations. It often happens that one has to deal with rare events, and the use of a variance reduction technique is almost mandatory, in order to have Monte Carlo efficient applications. The main issue associated with variance reduction techniques is related to the choice of the value of the biasing parameter. Actually, this task is typically left to the experience of the Monte Carlo user, who has to make many attempts before achieving an advantageous biasing. A valuable result is provided: a methodology and a practical rule addressed to establish an a priori guidance for the choice of the optimal value of the biasing parameter. This result, which has been obtained for a single component system, has the notable property of being valid for any multicomponent system. In particular, in this paper, the exponential and the uniform biases of exponentially distributed phenomena are investigated thoroughly

  20. Instructed fear stimuli bias visual attention

    NARCIS (Netherlands)

    Deltomme, Berre; Mertens, G.; Tibboel, Helen; Braem, Senne

    We investigated whether stimuli merely instructed to be fear-relevant can bias visual attention, even when the fear relation was never experienced before. Participants performed a dot-probe task with pictures of naturally fear-relevant (snake or spider) or -irrelevant (bird or butterfly) stimuli.

  1. Examining Gender Bias in Studies of Innovation

    OpenAIRE

    Crowden, N.

    2003-01-01

    This paper examines the presence of a gender bias in studies of innovation. Using the Innovation Systems Research Network (ISRN) and its interview guide as a case study, this research project examines how accurately and completely such innovation studies present gender differences in the innovation process.

  2. Attentional bias modification encourages healthy eating.

    Science.gov (United States)

    Kakoschke, Naomi; Kemps, Eva; Tiggemann, Marika

    2014-01-01

    The continual exposure to unhealthy food cues in the environment encourages poor dietary habits, in particular consuming too much fat and sugar, and not enough fruit and vegetables. According to Berridge's (2009) model of food reward, unhealthy eating is a behavioural response to biased attentional processing. The present study used an established attentional bias modification paradigm to discourage the consumption of unhealthy food and instead promote healthy eating. Participants were 146 undergraduate women who were randomly assigned to two groups: one was trained to direct their attention toward pictures of healthy food ('attend healthy' group) and the other toward unhealthy food ('attend unhealthy' group). It was found that participants trained to attend to healthy food cues demonstrated an increased attentional bias for such cues and ate relatively more of the healthy than unhealthy snacks compared to the 'attend unhealthy' group. Theoretically, the results support the postulated link between biased attentional processing and consumption (Berridge, 2009). At a practical level, they offer potential scope for interventions that focus on eating well. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Assessing Projection Bias in Consumers' Food Preferences.

    Directory of Open Access Journals (Sweden)

    Tiziana de-Magistris

    Full Text Available The aim of this study is to test whether projection bias exists in consumers' purchasing decisions for food products. To achieve our aim, we used a non-hypothetical experiment (i.e., experimental auction, where hungry and non-hungry participants were incentivized to reveal their willingness to pay (WTP. The results confirm the existence of projection bias when consumers made their decisions on food products. In particular, projection bias existed because currently hungry participants were willing to pay a higher price premium for cheeses than satiated ones, both in hungry and satiated future states. Moreover, participants overvalued the food product more when they were delivered in the future hungry condition than in the satiated one. Our study provides clear, quantitative and meaningful evidence of projection bias because our findings are based on economic valuation of food preferences. Indeed, the strength of this study is that findings are expressed in terms of willingness to pay which is an interpretable amount of money.

  4. Visual attention and the neuroimage bias.

    Directory of Open Access Journals (Sweden)

    D A Baker

    Full Text Available Several highly-cited experiments have presented evidence suggesting that neuroimages may unduly bias laypeople's judgments of scientific research. This finding has been especially worrisome to the legal community in which neuroimage techniques may be used to produce evidence of a person's mental state. However, a more recent body of work that has looked directly at the independent impact of neuroimages on layperson decision-making (both in legal and more general arenas, and has failed to find evidence of bias. To help resolve these conflicting findings, this research uses eye tracking technology to provide a measure of attention to different visual representations of neuroscientific data. Finding an effect of neuroimages on the distribution of attention would provide a potential mechanism for the influence of neuroimages on higher-level decisions. In the present experiment, a sample of laypeople viewed a vignette that briefly described a court case in which the defendant's actions might have been explained by a neurological defect. Accompanying these vignettes was either an MRI image of the defendant's brain, or a bar graph depicting levels of brain activity-two competing visualizations that have been the focus of much of the previous research on the neuroimage bias. We found that, while laypeople differentially attended to neuroimagery relative to the bar graph, this did not translate into differential judgments in a way that would support the idea of a neuroimage bias.

  5. Biased Allocation of Faces to Social Categories

    NARCIS (Netherlands)

    Dotsch, R.; Wigboldus, D.H.J.; Knippenberg, A.F.M. van

    2011-01-01

    Three studies show that social categorization is biased at the level of category allocation. In all studies, participants categorized faces. In Studies 1 and 2, participants overallocated faces with criminal features-a stereotypical negative trait-to the stigmatized Moroccan category, especially if

  6. Exchange bias mediated by interfacial nanoparticles (invited)

    Energy Technology Data Exchange (ETDEWEB)

    Berkowitz, A. E., E-mail: aberk@ucsd.edu [Department of Physics, University of California, San Diego, La Jolla, California 92093 (United States); Center for Magnetic Recording Research, University of California, California 92093 (United States); Sinha, S. K. [Department of Physics, University of California, San Diego, La Jolla, California 92093 (United States); Fullerton, E. E. [Center for Magnetic Recording Research, University of California, California 92093 (United States); Smith, D. J. [Department of Physics, Arizona State University, Tempe, Arizona 85287 (United States)

    2015-05-07

    The objective of this study on the iconic exchange-bias bilayer Permalloy/CoO has been to identify those elements of the interfacial microstructure and accompanying magnetic properties that are responsible for the exchange-bias and hysteretic properties of this bilayer. Both epitaxial and polycrystalline samples were examined. X-ray and neutron reflectometry established that there existed an interfacial region, of width ∼1 nm, whose magnetic properties differed from those of Py or CoO. A model was developed for the interfacial microstructure that predicts all the relevant properties of this system; namely; the temperature and Permalloy thickness dependence of the exchange-bias, H{sub EX}, and coercivity, H{sub C}; the much smaller measured values of H{sub EX} from what was nominally expected; the different behavior of H{sub EX} and H{sub C} in epitaxial and polycrystalline bilayers. A surprising result is that the exchange-bias does not involve direct exchange-coupling between Permalloy and CoO, but rather is mediated by CoFe{sub 2}O{sub 4} nanoparticles in the interfacial region.

  7. Rf-biasing of highly idealized plasmas

    NARCIS (Netherlands)

    Westermann, R.H.J.; Blauw, M.A.; Goedheer, W.J.; Sanden, van de M.C.M.; Schmidt, J.; Simek, M.; Pekarek, S.; Prukner, V.

    2007-01-01

    Remote plasmas, which are subjected to a radio-frequency (RF) biased surface, have been investigated theoretically and experimentally for decades. The relation between the complex power (DC) voltage characteristics, the ion energy distribution and control losses of the ion bombardment are of

  8. Cultural capital, teacher bias, and educational success

    DEFF Research Database (Denmark)

    Jæger, Mads Meier; Møllegaard, Stine

    2017-01-01

    . Second, cultural capital leads teachers to form upwardly biased perceptions of children's academic ability, but only when their exposure to children's cultural capital is brief (as in oral and written exams) rather than long (as in grades awarded at the end of the school year). Third, we find...

  9. Gender-Biased Communication in Physical Education

    Science.gov (United States)

    Valley, Julia A.; Graber, Kim C.

    2017-01-01

    Purpose: This study examined physical education teachers' awareness of gender equitable practices as well as the language and behaviors they employed in the physical education environment. The purpose of the study was to determine (a) what teachers know about gender equitable practices, (b) what types of gender bias are demonstrated, and (c) how…

  10. Apparent directional selection by biased pleiotropic mutation.

    Science.gov (United States)

    Tanaka, Yoshinari

    2010-07-01

    Pleiotropic effects of deleterious mutations are considered to be among the factors responsible for genetic constraints on evolution by long-term directional selection acting on a quantitative trait. If pleiotropic phenotypic effects are biased in a particular direction, mutations generate apparent directional selection, which refers to the covariance between fitness and the trait owing to a linear association between the number of mutations possessed by individuals and the genotypic values of the trait. The present analysis has shown how the equilibrium mean value of the trait is determined by a balance between directional selection and biased pleiotropic mutations. Assuming that genes act additively both on the trait and on fitness, the total variance-standardized directional selection gradient was decomposed into apparent and true components. Experimental data on mutation bias from the bristle traits of Drosophila and life history traits of Daphnia suggest that apparent selection explains a small but significant fraction of directional selection pressure that is observed in nature; the data suggest that changes induced in a trait by biased pleiotropic mutation (i.e., by apparent directional selection) are easily compensated for by (true) directional selection.

  11. Vowel bias in Danish word-learning

    DEFF Research Database (Denmark)

    Højen, Anders; Nazzi, Thierry

    2016-01-01

    The present study explored whether the phonological bias favoring consonants found in French-learning infants and children when learning new words (Havy & Nazzi, 2009; Nazzi, 2005) is language-general, as proposed by Nespor, Peña and Mehler (2003), or varies across languages, perhaps as a functio...

  12. Bias in emerging biomarkers for bipolar disorder

    DEFF Research Database (Denmark)

    Carvalho, A F; Köhler, C A; Fernandes, B S

    2016-01-01

    BACKGROUND: To date no comprehensive evaluation has appraised the likelihood of bias or the strength of the evidence of peripheral biomarkers for bipolar disorder (BD). Here we performed an umbrella review of meta-analyses of peripheral non-genetic biomarkers for BD. METHOD: The Pubmed/Medline, E...

  13. Quantifying retrieval bias in Web archive search

    NARCIS (Netherlands)

    Samar, Thaer; Traub, Myriam C.; van Ossenbruggen, Jacco; Hardman, Lynda; de Vries, Arjen P.

    2018-01-01

    A Web archive usually contains multiple versions of documents crawled from the Web at different points in time. One possible way for users to access a Web archive is through full-text search systems. However, previous studies have shown that these systems can induce a bias, known as the

  14. Referral bias in ALS epidemiological studies.

    Science.gov (United States)

    Logroscino, Giancarlo; Marin, Benoit; Piccininni, Marco; Arcuti, Simona; Chiò, Adriano; Hardiman, Orla; Rooney, James; Zoccolella, Stefano; Couratier, Philippe; Preux, Pierre-Marie; Beghi, Ettore

    2018-01-01

    Despite concerns about the representativeness of patients from ALS tertiary centers as compared to the ALS general population, the extent of referral bias in clinical studies remains largely unknown. Using data from EURALS consortium we aimed to assess nature, extent and impact of referral bias. Four European ALS population-based registries located in Ireland, Piedmont, Puglia, Italy, and Limousin, France, covering 50 million person-years, participated. Demographic and clinic characteristics of ALS patients diagnosed in tertiary referral centers were contrasted with the whole ALS populations enrolled in registries in the same geographical areas. Patients referred to ALS centers were younger (with difference ranging from 1.1 years to 2.4 years), less likely to present a bulbar onset, with a higher proportion of familial antecedents and a longer survival (ranging from 11% to 15%) when compared to the entire ALS population in the same geographic area. A trend for referral bias is present in cohorts drawn from ALS referral centers. The magnitude of the possible referral bias in a particular tertiary center can be estimated through a comparison with ALS patients drawn from registry in the same geographic area. Studies based on clinical cohorts should be cautiously interpreted. The presence of a registry in the same area may improve the complete ascertainment in the referral center.

  15. Avoiding bias in safety testing design

    DEFF Research Database (Denmark)

    Calow, Peter

    2011-01-01

    All scientists are biased, no matter what their backgrounds or affiliations, so what is it about the scientific method that overcomes this and which makes science so successful? Key features are transparency and critical peer scrutiny. These general issues will be will be considered in terms...

  16. Cognitive bias measurement and social anxiety disorder: Correlating self-report data and attentional bias

    Directory of Open Access Journals (Sweden)

    Alexander Miloff

    2015-09-01

    Full Text Available Social anxiety disorder (SAD and attentional bias are theoretically connected in cognitive behavioral therapeutic models. In fact, there is an emerging field focusing on modifying attentional bias as a stand-alone treatment. However, it is unclear to what degree these attentional biases are present before commencing treatment. The purpose of this study was to measure pre-treatment attentional bias in 153 participants diagnosed with SAD using a home-based Internet version of the dot-probe paradigm. Results showed no significant correlation for attentional bias (towards or away from negative words or faces and the self-rated version of the Liebowitz Social Anxiety Scale (LSAS-SR. However, two positive correlations were found for the secondary measures Generalized Anxiety Disorder 7 (GAD-7 and Patient Health Questionnaire 9 (PHQ-9. These indicated that those with elevated levels of anxiety and depression had a higher bias towards negative faces in neutral–negative and positive–negative valence combinations, respectively. The unreliability of the dot-probe paradigm and home-based Internet delivery are discussed to explain the lack of correlations between LSAS-SR and attentional bias. Changes to the dot-probe task are suggested that could improve reliability.

  17. Quantifying Heuristic Bias: Anchoring, Availability, and Representativeness.

    Science.gov (United States)

    Richie, Megan; Josephson, S Andrew

    2018-01-01

    Construct: Authors examined whether a new vignette-based instrument could isolate and quantify heuristic bias. Heuristics are cognitive shortcuts that may introduce bias and contribute to error. There is no standardized instrument available to quantify heuristic bias in clinical decision making, limiting future study of educational interventions designed to improve calibration of medical decisions. This study presents validity data to support a vignette-based instrument quantifying bias due to the anchoring, availability, and representativeness heuristics. Participants completed questionnaires requiring assignment of probabilities to potential outcomes of medical and nonmedical scenarios. The instrument randomly presented scenarios in one of two versions: Version A, encouraging heuristic bias, and Version B, worded neutrally. The primary outcome was the difference in probability judgments for Version A versus Version B scenario options. Of 167 participants recruited, 139 enrolled. Participants assigned significantly higher mean probability values to Version A scenario options (M = 9.56, SD = 3.75) than Version B (M = 8.98, SD = 3.76), t(1801) = 3.27, p = .001. This result remained significant analyzing medical scenarios alone (Version A, M = 9.41, SD = 3.92; Version B, M = 8.86, SD = 4.09), t(1204) = 2.36, p = .02. Analyzing medical scenarios by heuristic revealed a significant difference between Version A and B for availability (Version A, M = 6.52, SD = 3.32; Version B, M = 5.52, SD = 3.05), t(404) = 3.04, p = .003, and representativeness (Version A, M = 11.45, SD = 3.12; Version B, M = 10.67, SD = 3.71), t(396) = 2.28, p = .02, but not anchoring. Stratifying by training level, students maintained a significant difference between Version A and B medical scenarios (Version A, M = 9.83, SD = 3.75; Version B, M = 9.00, SD = 3.98), t(465) = 2.29, p = .02, but not residents or attendings. Stratifying by heuristic and training level, availability maintained

  18. A New Source Biasing Approach in ADVANTG

    International Nuclear Information System (INIS)

    Bevill, Aaron M.; Mosher, Scott W.

    2012-01-01

    The ADVANTG code has been developed at Oak Ridge National Laboratory to generate biased sources and weight window maps for MCNP using the CADIS and FW-CADIS methods. In preparation for an upcoming RSICC release, a new approach for generating a biased source has been developed. This improvement streamlines user input and improves reliability. Previous versions of ADVANTG generated the biased source from ADVANTG input, writing an entirely new general fixed-source definition (SDEF). Because volumetric sources were translated into SDEF-format as a finite set of points, the user had to perform a convergence study to determine whether the number of source points used accurately represented the source region. Further, the large number of points that must be written in SDEF-format made the MCNP input and output files excessively long and difficult to debug. ADVANTG now reads SDEF-format distributions and generates corresponding source biasing cards, eliminating the need for a convergence study. Many problems of interest use complicated source regions that are defined using cell rejection. In cell rejection, the source distribution in space is defined using an arbitrarily complex cell and a simple bounding region. Source positions are sampled within the bounding region but accepted only if they fall within the cell; otherwise, the position is resampled entirely. When biasing in space is applied to sources that use rejection sampling, current versions of MCNP do not account for the rejection in setting the source weight of histories, resulting in an 'unfair game'. This problem was circumvented in previous versions of ADVANTG by translating volumetric sources into a finite set of points, which does not alter the mean history weight ((bar w)). To use biasing parameters without otherwise modifying the original cell-rejection SDEF-format source, ADVANTG users now apply a correction factor for (bar w) in post-processing. A stratified-random sampling approach in ADVANTG is under

  19. Influence of compulsivity of drug abuse on dopaminergic modulation of attentional bias in stimulant dependence.

    Science.gov (United States)

    Ersche, Karen D; Bullmore, Edward T; Craig, Kevin J; Shabbir, Shaila S; Abbott, Sanja; Müller, Ulrich; Ooi, Cinly; Suckling, John; Barnes, Anna; Sahakian, Barbara J; Merlo-Pich, Emilio V; Robbins, Trevor W

    2010-06-01

    There are no effective pharmacotherapies for stimulant dependence but there are many plausible targets for development of novel therapeutics. We hypothesized that dopamine-related targets are relevant for treatment of stimulant dependence, and there will likely be individual differences in response to dopaminergic challenges. To measure behavioral and brain functional markers of drug-related attentional bias in stimulant-dependent individuals studied repeatedly after short-term dosing with dopamine D(2)/D(3) receptor antagonist and agonist challenges. Randomized, double-blind, placebo-controlled, parallel-groups, crossover design using pharmacological functional magnetic resonance imaging. Clinical research unit (GlaxoSmithKline) and local community in Cambridge, England. Stimulant-dependent individuals (n = 18) and healthy volunteers (n = 18). Amisulpride (400 mg), pramipexole dihydrochloride (0.5 mg), or placebo were administered in counterbalanced order at each of 3 repeated testing sessions. Attentional bias for stimulant-related words was measured during functional magnetic resonance imaging by a drug-word Stroop paradigm; trait impulsivity and compulsivity of dependence were assessed at baseline by questionnaire. Drug users demonstrated significant attentional bias for drug-related words, which was correlated with greater activation of the left prefrontal and right cerebellar cortex. Attentional bias was greater in people with highly compulsive patterns of stimulant abuse; the effects of dopaminergic challenges on attentional interference and related frontocerebellar activation were different between high- and low-compulsivity subgroups. Greater attentional bias for and greater prefrontal activation by stimulant-related words constitute a candidate neurocognitive marker for dependence. Individual differences in compulsivity of stimulant dependence had significant effects on attentional bias, its brain functional representation, and its short-term modulation

  20. Manipulation of Very Few Receptor Discriminator Residues Greatly Enhances Receptor Specificity of Non-visual Arrestins*

    Science.gov (United States)

    Gimenez, Luis E.; Vishnivetskiy, Sergey A.; Baameur, Faiza; Gurevich, Vsevolod V.

    2012-01-01

    Based on the identification of residues that determine receptor selectivity of arrestins and the analysis of the evolution in the arrestin family, we introduced 10 mutations of “receptor discriminator” residues in arrestin-3. The recruitment of these mutants to M2 muscarinic (M2R), D1 (D1R) and D2 (D2R) dopamine, and β2-adrenergic receptors (β2AR) was assessed using bioluminescence resonance energy transfer-based assays in cells. Seven of 10 mutations differentially affected arrestin-3 binding to individual receptors. D260K and Q262P reduced the binding to β2AR, much more than to other receptors. The combination D260K/Q262P virtually eliminated β2AR binding while preserving the interactions with M2R, D1R, and D2R. Conversely, Y239T enhanced arrestin-3 binding to β2AR and reduced the binding to M2R, D1R, and D2R, whereas Q256Y selectively reduced recruitment to D2R. The Y239T/Q256Y combination virtually eliminated the binding to D2R and reduced the binding to β2AR and M2R, yielding a mutant with high selectivity for D1R. Eleven of 12 mutations significantly changed the binding to light-activated phosphorhodopsin. Thus, manipulation of key residues on the receptor-binding surface modifies receptor preference, enabling the construction of non-visual arrestins specific for particular receptor subtypes. These findings pave the way to the construction of signaling-biased arrestins targeting the receptor of choice for research or therapeutic purposes. PMID:22787152

  1. Manipulation of very few receptor discriminator residues greatly enhances receptor specificity of non-visual arrestins.

    Science.gov (United States)

    Gimenez, Luis E; Vishnivetskiy, Sergey A; Baameur, Faiza; Gurevich, Vsevolod V

    2012-08-24

    Based on the identification of residues that determine receptor selectivity of arrestins and the analysis of the evolution in the arrestin family, we introduced 10 mutations of "receptor discriminator" residues in arrestin-3. The recruitment of these mutants to M2 muscarinic (M2R), D1 (D1R) and D2 (D2R) dopamine, and β(2)-adrenergic receptors (β(2)AR) was assessed using bioluminescence resonance energy transfer-based assays in cells. Seven of 10 mutations differentially affected arrestin-3 binding to individual receptors. D260K and Q262P reduced the binding to β(2)AR, much more than to other receptors. The combination D260K/Q262P virtually eliminated β(2)AR binding while preserving the interactions with M2R, D1R, and D2R. Conversely, Y239T enhanced arrestin-3 binding to β(2)AR and reduced the binding to M2R, D1R, and D2R, whereas Q256Y selectively reduced recruitment to D2R. The Y239T/Q256Y combination virtually eliminated the binding to D2R and reduced the binding to β(2)AR and M2R, yielding a mutant with high selectivity for D1R. Eleven of 12 mutations significantly changed the binding to light-activated phosphorhodopsin. Thus, manipulation of key residues on the receptor-binding surface modifies receptor preference, enabling the construction of non-visual arrestins specific for particular receptor subtypes. These findings pave the way to the construction of signaling-biased arrestins targeting the receptor of choice for research or therapeutic purposes.

  2. Single-Receiver GPS Phase Bias Resolution

    Science.gov (United States)

    Bertiger, William I.; Haines, Bruce J.; Weiss, Jan P.; Harvey, Nathaniel E.

    2010-01-01

    Existing software has been modified to yield the benefits of integer fixed double-differenced GPS-phased ambiguities when processing data from a single GPS receiver with no access to any other GPS receiver data. When the double-differenced combination of phase biases can be fixed reliably, a significant improvement in solution accuracy is obtained. This innovation uses a large global set of GPS receivers (40 to 80 receivers) to solve for the GPS satellite orbits and clocks (along with any other parameters). In this process, integer ambiguities are fixed and information on the ambiguity constraints is saved. For each GPS transmitter/receiver pair, the process saves the arc start and stop times, the wide-lane average value for the arc, the standard deviation of the wide lane, and the dual-frequency phase bias after bias fixing for the arc. The second step of the process uses the orbit and clock information, the bias information from the global solution, and only data from the single receiver to resolve double-differenced phase combinations. It is called "resolved" instead of "fixed" because constraints are introduced into the problem with a finite data weight to better account for possible errors. A receiver in orbit has much shorter continuous passes of data than a receiver fixed to the Earth. The method has parameters to account for this. In particular, differences in drifting wide-lane values must be handled differently. The first step of the process is automated, using two JPL software sets, Longarc and Gipsy-Oasis. The resulting orbit/clock and bias information files are posted on anonymous ftp for use by any licensed Gipsy-Oasis user. The second step is implemented in the Gipsy-Oasis executable, gd2p.pl, which automates the entire process, including fetching the information from anonymous ftp

  3. New Trends in Magnetic Exchange Bias

    Science.gov (United States)

    Mougin, Alexandra; Mangin, Stéphane; Bobo, Jean-Francois; Loidl, Alois

    2005-05-01

    The study of layered magnetic structures is one of the hottest topics in magnetism due to the growing attraction of applications in magnetic sensors and magnetic storage media, such as random access memory. For almost half a century, new discoveries have driven researchers to re-investigate magnetism in thin film structures. Phenomena such as giant magnetoresistance, tunneling magnetoresistance, exchange bias and interlayer exchange coupling led to new ideas to construct devices, based not only on semiconductors but on a variety of magnetic materials Upon cooling fine cobalt particles in a magnetic field through the Néel temperature of their outer antiferromagnetic oxide layer, Meiklejohn and Bean discovered exchange bias in 1956. The exchange bias effect through which an antiferromagnetic AF layer can cause an adjacent ferromagnetic F layer to develop a preferred direction of magnetization, is widely used in magnetoelectronics technology to pin the magnetization of a device reference layer in a desired direction. However, the origin and effects due to exchange interaction across the interface between antiferromagneic and ferromagnetic layers are still debated after about fifty years of research, due to the extreme difficulty associated with the determination of the magnetic interfacial structure in F/AF bilayers. Indeed, in an AF/F bilayer system, the AF layer acts as “the invisible man” during conventional magnetic measurements and the presence of the exchange coupling is evidenced indirectly through the unusual behavior of the adjacent F layer. Basically, the coercive field of the F layer increases in contact with the AF and, in some cases, its hysteresis loop is shifted by an amount called exchange bias field. Thus, AF/F exchange coupling generates a new source of anisotropy in the F layer. This induced anisotropy strongly depends on basic features such as the magnetocrystalline anisotropy, crystallographic and spin structures, defects, domain patterns etc

  4. Bond and Equity Home Bias and Foreign Bias: an International Study

    OpenAIRE

    VanPée, Rosanne; De Moor, Lieven

    2012-01-01

    In this paper we explore tentatively and formally the differences between bond and equity home bias and foreign bias based on one large scale dataset including developed and emerging markets for the period 2001 to 2010. We set the stage by tentatively and formally linking the diversion of bond and equity home bias in OECD countries to the increasing public debt issues under the form of government bonds i.e. the supply-driven argument. Unlike Fidora et al. (2007) we do not find that exchange r...

  5. Recognizing and reducing cognitive bias in clinical and forensic neurology.

    Science.gov (United States)

    Satya-Murti, Saty; Lockhart, Joseph

    2015-10-01

    In medicine, cognitive errors form the basis of bias in clinical practice. Several types of bias are common and pervasive, and may lead to inaccurate diagnosis or treatment. Forensic and clinical neurology, even when aided by current technologies, are still dependent on cognitive interpretations, and therefore prone to bias. This article discusses 4 common biases that can lead the clinician astray. They are confirmation bias (selective gathering of and neglect of contradictory evidence); base rate bias (ignoring or misusing prevailing base rate data); hindsight bias (oversimplification of past causation); and good old days bias (the tendency for patients to misremember and exaggerate their preinjury functioning). We briefly describe strategies adopted from the field of psychology that could minimize bias. While debiasing is not easy, reducing such errors requires awareness and acknowledgment of our susceptibility to these cognitive distortions.

  6. Receptor-receptor interactions within receptor mosaics. Impact on neuropsychopharmacology.

    Science.gov (United States)

    Fuxe, K; Marcellino, D; Rivera, A; Diaz-Cabiale, Z; Filip, M; Gago, B; Roberts, D C S; Langel, U; Genedani, S; Ferraro, L; de la Calle, A; Narvaez, J; Tanganelli, S; Woods, A; Agnati, L F

    2008-08-01

    Future therapies for diseases associated with altered dopaminergic signaling, including Parkinson's disease, schizophrenia and drug addiction or drug dependence may substantially build on the existence of intramembrane receptor-receptor interactions within dopamine receptor containing receptor mosaics (RM; dimeric or high-order receptor oligomers) where it is believed that the dopamine D(2) receptor may operate as the 'hub receptor' within these complexes. The constitutive adenosine A(2A)/dopamine D(2) RM, located in the dorsal striato-pallidal GABA neurons, are of particular interest in view of the demonstrated antagonistic A(2A)/D(2) interaction within these heteromers; an interaction that led to the suggestion and later demonstration that A(2A) antagonists could be used as novel anti-Parkinsonian drugs. Based on the likely existence of A(2A)/D(2)/mGluR5 RM located both extrasynaptically on striato-pallidal GABA neurons and on cortico-striatal glutamate terminals, multiple receptor-receptor interactions within this RM involving synergism between A(2A)/mGluR5 to counteract D(2) signaling, has led to the proposal of using combined mGluR5 and A(2A) antagonists as a future anti-Parkinsonian treatment. Based on the same RM in the ventral striato-pallidal GABA pathways, novel strategies for the treatment of schizophrenia, building on the idea that A(2A) agonists and/or mGluR5 agonists will help reduce the increased dopaminergic signaling associated with this disease, have been suggested. Such treatment may ensure the proper glutamatergic drive from the mediodorsal thalamic nucleus to the prefrontal cortex, one which is believed to be reduced in schizophrenia due to a dominance of D(2)-like signaling in the ventral striatum. Recently, A(2A) receptors also have been shown to counteract the locomotor and sensitizing actions of cocaine and increases in A(2A) receptors have also been observed in the nucleus accumbens after extended cocaine self-administration, probably

  7. Are most samples of animals systematically biased? Consistent individual trait differences bias samples despite random sampling.

    Science.gov (United States)

    Biro, Peter A

    2013-02-01

    Sampling animals from the wild for study is something nearly every biologist has done, but despite our best efforts to obtain random samples of animals, 'hidden' trait biases may still exist. For example, consistent behavioral traits can affect trappability/catchability, independent of obvious factors such as size and gender, and these traits are often correlated with other repeatable physiological and/or life history traits. If so, systematic sampling bias may exist for any of these traits. The extent to which this is a problem, of course, depends on the magnitude of bias, which is presently unknown because the underlying trait distributions in populations are usually unknown, or unknowable. Indeed, our present knowledge about sampling bias comes from samples (not complete population censuses), which can possess bias to begin with. I had the unique opportunity to create naturalized populations of fish by seeding each of four small fishless lakes with equal densities of slow-, intermediate-, and fast-growing fish. Using sampling methods that are not size-selective, I observed that fast-growing fish were up to two-times more likely to be sampled than slower-growing fish. This indicates substantial and systematic bias with respect to an important life history trait (growth rate). If correlations between behavioral, physiological and life-history traits are as widespread as the literature suggests, then many animal samples may be systematically biased with respect to these traits (e.g., when collecting animals for laboratory use), and affect our inferences about population structure and abundance. I conclude with a discussion on ways to minimize sampling bias for particular physiological/behavioral/life-history types within animal populations.

  8. Mood-congruent free recall bias in anxious individuals is not a consequence of response bias

    OpenAIRE

    Russo, Riccardo; Whittuck, Dora; Roberson, Debi; Dutton, Kevin; Georgiou, George; Fox, Elaine

    2006-01-01

    The status of mood-congruent free recall bias in anxious individuals was evaluated following incidental encoding of target words. Individuals with high and low levels of trait anxiety completed a modified Stroop task, which revealed an attentional bias for threat-related stimuli in anxious individuals. This group was significantly slower in naming the colour in which threat-related words were displayed compared to neutral words. In a subsequent free recall test for the words used in the modif...

  9. Is racial bias malleable? Whites' lay theories of racial bias predict divergent strategies for interracial interactions.

    Science.gov (United States)

    Neel, Rebecca; Shapiro, Jenessa R

    2012-07-01

    How do Whites approach interracial interactions? We argue that a previously unexamined factor-beliefs about the malleability of racial bias-guides Whites' strategies for difficult interracial interactions. We predicted and found that those who believe racial bias is malleable favor learning-oriented strategies such as taking the other person's perspective and trying to learn why an interaction is challenging, whereas those who believe racial bias is fixed favor performance-oriented strategies such as overcompensating in the interaction and trying to end the interaction as quickly as possible. Four studies support these predictions. Whether measured (Studies 1, 3, and 4) or manipulated (Study 2), beliefs that racial bias is fixed versus malleable yielded these divergent strategies for difficult interracial interactions. Furthermore, beliefs about the malleability of racial bias are distinct from related constructs (e.g., prejudice and motivations to respond without prejudice; Studies 1, 3, and 4) and influence self-reported (Studies 1-3) and actual (Study 4) strategies in imagined (Studies 1-2) and real (Studies 3-4) interracial interactions. Together, these findings demonstrate that beliefs about the malleability of racial bias influence Whites' approaches to and strategies within interracial interactions. PsycINFO Database Record (c) 2012 APA, all rights reserved

  10. Group rationale, collective sense: beyond intergroup bias.

    Science.gov (United States)

    Spears, Russell

    2010-03-01

    In this paper, I contest the view of the group as a source of bias and irrationality, especially prevalent within social psychology. I argue that this negative evaluation often arises by applying inappropriate standards, relating to the wrong level of analysis (often the individual level). Second, the image of the group as bad and biasing is often overstated. For example, the evidence suggests that intergroup discrimination, rather than being universal or generic, is often constrained, proportionate and reflects functional and rational strategies for managing threats and opportunities at the group level. Third, although the recent upsurge of interest in group emotions could be seen to reinforce the dualism between rationality and emotion, the contemporary functional approach argues for group emotions as augmenting rather than contradicting rationality. However, we should be wary (and weary) of narrow economic and individualist notions of rationality; group identity may offer the opportunity to redefine rationality in more collective and prosocial ways.

  11. Moisture Forecast Bias Correction in GEOS DAS

    Science.gov (United States)

    Dee, D.

    1999-01-01

    Data assimilation methods rely on numerous assumptions about the errors involved in measuring and forecasting atmospheric fields. One of the more disturbing of these is that short-term model forecasts are assumed to be unbiased. In case of atmospheric moisture, for example, observational evidence shows that the systematic component of errors in forecasts and analyses is often of the same order of magnitude as the random component. we have implemented a sequential algorithm for estimating forecast moisture bias from rawinsonde data in the Goddard Earth Observing System Data Assimilation System (GEOS DAS). The algorithm is designed to remove the systematic component of analysis errors and can be easily incorporated in an existing statistical data assimilation system. We will present results of initial experiments that show a significant reduction of bias in the GEOS DAS moisture analyses.

  12. Conflict of interest and bias in publication.

    Science.gov (United States)

    Macklin, Ruth

    2016-01-01

    In his excellent article about commercial conflict of interest, Mark Wilson quotes Dennis Thompson, a political scientist who provided a searching analysis of the concept of conflict of interest (Col). Using Thompson's analysis, Wilson writes: "Determining whether factors such as ambition, the pursuit of fame and financial gain had biased a judgment was challenging. Motives are not always clear to either the conflicted party or to an outside observer." In this commentary, I aim to broaden the discussion beyond the narrowly commercial aspects of Col. I argue that bias can be introduced in major scientific journals by the editors' choices and policies. The context is a controversy that erupted in 2013 over the adequacy of informed consent in a clinical trial involving extremely premature infants. In this, as in Wilson's example, the players included the New England Journal of Medicine (NEJM), as well as the highest officials of the US National Institutes of Health (NIH).

  13. Calibration biases in logical reasoning tasks

    Directory of Open Access Journals (Sweden)

    Guillermo Macbeth

    2013-08-01

    Full Text Available The aim of this contribution is to present an experimental study about calibration in deductive reasoning tasks. Calibration is defi ned as the empirical convergence or divergence between the objective and the subjective success. The underconfi dence bias is understood as the dominance of the former over the latter. The hypothesis of this study states that the form of the propositions presented in the experiment is critical for calibration phenomena. Affi rmative and negative propositions are distinguished in their cognitive processing. Results suggests that monotonous compound propositions are prone to underconfi dence. An heuristic approach to this phenomenon is proposed. The activation of a monotony heuristic would produce an illusion of simplicity that generates the calibration bias. These evidence is analysed in the context of the metacognitive modeling of calibration phenomena.

  14. Gender bias in scholarly peer review.

    Science.gov (United States)

    Helmer, Markus; Schottdorf, Manuel; Neef, Andreas; Battaglia, Demian

    2017-03-21

    Peer review is the cornerstone of scholarly publishing and it is essential that peer reviewers are appointed on the basis of their expertise alone. However, it is difficult to check for any bias in the peer-review process because the identity of peer reviewers generally remains confidential. Here, using public information about the identities of 9000 editors and 43000 reviewers from the Frontiers series of journals, we show that women are underrepresented in the peer-review process, that editors of both genders operate with substantial same-gender preference (homophily), and that the mechanisms of this homophily are gender-dependent. We also show that homophily will persist even if numerical parity between genders is reached, highlighting the need for increased efforts to combat subtler forms of gender bias in scholarly publishing.

  15. Human language reveals a universal positivity bias.

    Science.gov (United States)

    Dodds, Peter Sheridan; Clark, Eric M; Desu, Suma; Frank, Morgan R; Reagan, Andrew J; Williams, Jake Ryland; Mitchell, Lewis; Harris, Kameron Decker; Kloumann, Isabel M; Bagrow, James P; Megerdoomian, Karine; McMahon, Matthew T; Tivnan, Brian F; Danforth, Christopher M

    2015-02-24

    Using human evaluation of 100,000 words spread across 24 corpora in 10 languages diverse in origin and culture, we present evidence of a deep imprint of human sociality in language, observing that (i) the words of natural human language possess a universal positivity bias, (ii) the estimated emotional content of words is consistent between languages under translation, and (iii) this positivity bias is strongly independent of frequency of word use. Alongside these general regularities, we describe interlanguage variations in the emotional spectrum of languages that allow us to rank corpora. We also show how our word evaluations can be used to construct physical-like instruments for both real-time and offline measurement of the emotional content of large-scale texts.

  16. Is there gender bias in nursing research?

    Science.gov (United States)

    Polit, Denise F; Beck, Cheryl Tatano

    2008-10-01

    Using data from a consecutive sample of 259 studies published in four leading nursing research journals in 2005-2006, we examined whether nurse researchers favor females as study participants. On average, 75.3% of study participants were female, and 38% of studies had all-female samples. The bias favoring female participants was statistically significant and persistent. The bias was observed regardless of funding source, methodological features, and other participant and researcher characteristics, with one exception: studies that had male investigators had more sex-balanced samples. When designing studies, nurse researchers need to pay close attention to who will benefit from their research and to whether they are leaving out a specific group about which there is a gap in knowledge. (c) 2008 Wiley Periodicals, Inc.

  17. Bias During the Evaluation of Animal Studies?

    Science.gov (United States)

    Knight, Andrew

    2012-02-23

    My recent book entitled The Costs and Benefits of Animal Experiments seeks to answer a key question within animal ethics, namely: is animal experimentation ethically justifiable? Or, more precisely, is it justifiable within the utilitarian cost:benefit framework that fundamentally underpins most regulations governing animal experimentation? To answer this question I reviewed more than 500 scientific publications describing animal studies, animal welfare impacts, and alternative research, toxicity testing and educational methodologies. To minimise bias I focused primarily on large-scale systematic reviews that had examined the human clinical and toxicological utility of animal studies. Despite this, Dr. Susanne Prankel recently reviewed my book in this journal, essentially accusing me of bias. However, she failed to provide any substantive evidence to refute my conclusions, let alone evidence of similar weight to that on which they are based. Those conclusions are, in fact, firmly based on utilitarian ethical reasoning, informed by scientific evidence of considerable strength, and I believe they are robust.

  18. Heterogeneous Causal Effects and Sample Selection Bias

    DEFF Research Database (Denmark)

    Breen, Richard; Choi, Seongsoo; Holm, Anders

    2015-01-01

    The role of education in the process of socioeconomic attainment is a topic of long standing interest to sociologists and economists. Recently there has been growing interest not only in estimating the average causal effect of education on outcomes such as earnings, but also in estimating how...... causal effects might vary over individuals or groups. In this paper we point out one of the under-appreciated hazards of seeking to estimate heterogeneous causal effects: conventional selection bias (that is, selection on baseline differences) can easily be mistaken for heterogeneity of causal effects....... This might lead us to find heterogeneous effects when the true effect is homogenous, or to wrongly estimate not only the magnitude but also the sign of heterogeneous effects. We apply a test for the robustness of heterogeneous causal effects in the face of varying degrees and patterns of selection bias...

  19. Decisional Bias as Implicit Moral Judgment

    Science.gov (United States)

    Spring, Toni; Saltzstein, Herbert D.

    2017-01-01

    Decisional bias (false alarm rate) when judging the guilt/innocence of a suspect is offered as an implicit measure of moral judgment. Combining two data sets, 215 participants, ages 10-12, 13-15, and 16-18 watched the visually identical film involving a person setting a fire, framed either as (1) intentional but not resulting in a fire (BI-NF),…

  20. Limiter biasing experiments on the tokamak ISTTOK

    Czech Academy of Sciences Publication Activity Database

    Silva, C.; Nedzelskiy, I.; Figueiredo, H.; Cabral, J. A. C.; Varandas, C. A. F.; Stöckel, Jan

    2003-01-01

    Roč. 53, č. 10 (2003), s. 937-944 ISSN 0011-4626. [Workshop "Electric Fields Structures and Relaxation in Edge Plasmas"/6th./. St. Petersburg, 13.06.2003-14.06.2003] Institutional research plan: CEZ:AV0Z2043910 Keywords : biasing, edge plasma, particle confinement Subject RIV: BL - Plasma and Gas Discharge Physics Impact factor: 0.263, year: 2003

  1. Automation bias: empirical results assessing influencing factors.

    Science.gov (United States)

    Goddard, Kate; Roudsari, Abdul; Wyatt, Jeremy C

    2014-05-01

    To investigate the rate of automation bias - the propensity of people to over rely on automated advice and the factors associated with it. Tested factors were attitudinal - trust and confidence, non-attitudinal - decision support experience and clinical experience, and environmental - task difficulty. The paradigm of simulated decision support advice within a prescribing context was used. The study employed within participant before-after design, whereby 26 UK NHS General Practitioners were shown 20 hypothetical prescribing scenarios with prevalidated correct and incorrect answers - advice was incorrect in 6 scenarios. They were asked to prescribe for each case, followed by being shown simulated advice. Participants were then asked whether they wished to change their prescription, and the post-advice prescription was recorded. Rate of overall decision switching was captured. Automation bias was measured by negative consultations - correct to incorrect prescription switching. Participants changed prescriptions in 22.5% of scenarios. The pre-advice accuracy rate of the clinicians was 50.38%, which improved to 58.27% post-advice. The CDSS improved the decision accuracy in 13.1% of prescribing cases. The rate of automation bias, as measured by decision switches from correct pre-advice, to incorrect post-advice was 5.2% of all cases - a net improvement of 8%. More immediate factors such as trust in the specific CDSS, decision confidence, and task difficulty influenced rate of decision switching. Lower clinical experience was associated with more decision switching. Age, DSS experience and trust in CDSS generally were not significantly associated with decision switching. This study adds to the literature surrounding automation bias in terms of its potential frequency and influencing factors. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  2. Substitution biases in price indices during transition

    Czech Academy of Sciences Publication Activity Database

    Hanousek, Jan; Filer, Randall K.

    2004-01-01

    Roč. 21, č. 2 (2004), s. 167-177 ISSN 0167-8000 R&D Projects: GA MŠk ME 595 Institutional research plan: CEZ:AV0Z7085904 Keywords : price liberalization * substitution bias * transition economies Subject RIV: AH - Economics http://search. ebscohost .com/login.aspx?direct=true&db=a9h&AN=17109091&site=ehost-live

  3. Students' gender bias in teaching evaluations

    OpenAIRE

    Punyanunt-Carter, Narissra; Carter, Stacy L.

    2015-01-01

    The goal of this study was to investigate if there is gender bias in student evaluations. Researchers administered a modified version of the teacher evaluation forms to 58 students (male=30; female=28) in a basic introductory communications class. Half the class was instructed to fill out the survey about a male professor, and the other half a female professor. Researchers broke down the evaluation results question by question in order to give a detailed account of the findings. Results revea...

  4. Costs, biases and betting markets: new evidence

    OpenAIRE

    Michael A. Smith; David Paton; Leighton Vaughan-Williams

    2004-01-01

    In recent years, person-to-person wagering on Internet ‘betting exchanges’ (sometimes known as ‘matched betting’) has become an increasingly important medium for betting on horse racing, sports and special events. Established gambling operators have argued that betting exchanges should not be allowed on the grounds that they represent unfair competition. In this paper, we argue that, in fact, betting exchanges have brought about reductions in traditional market biases and significant efficien...

  5. Edge biasing in the WEGA stellarator

    International Nuclear Information System (INIS)

    Lischtschenko, Oliver

    2009-01-01

    The WEGA stellarator is used to confine low temperature, overdense (densities exceeding the cut-off density of the heating wave) plasmas by magnetic fields in the range of B=50-500 mT. Microwave heating systems are used to ignite gas discharges using hydrogen, helium, neon or argon as working gases. The produced plasmas have been analyzed using Langmuir and emissive probes, a single-channel interferometer and ultra-high resolution Doppler spectroscopy. For a typical argon discharge in the low field operation, B=56 mT, the maximum electron density is n e ∝10 18 m -3 with temperatures in the range of T=4-12 eV. The plasma parameters are determined by using Langmuir probes and are cross-checked with interferometry. It is demonstrated within this work that the joint use of emissive probes and ultra-high resolution Doppler spectroscopy allows a precise measurement of the radial electric field. The focus of this work is on demonstrating the ability to modify the existing radial electric field in a plasma by using the biasing probe. This work commences with a basic approach and first establishes the diagnostic tools in a well-known discharge. Then the perturbation caused by the biasing probe is assessed. Following the characterization of the unperturbed plasmas, plasma states altered by the operation of the energized biasing probe are characterized. During biasing the plasma two different stable plasma states have been found. The two observed plasma states differ in plasma parameter profiles, such as density, temperature, electric field and confined energy. (orig.)

  6. Acetylcholine receptor antibody

    Science.gov (United States)

    ... medlineplus.gov/ency/article/003576.htm Acetylcholine receptor antibody To use the sharing features on this page, please enable JavaScript. Acetylcholine receptor antibody is a protein found in the blood of ...

  7. Immediacy bias in social-emotional comparisons.

    Science.gov (United States)

    White, Katherine; Van Boven, Leaf

    2012-08-01

    In seven studies of naturally occurring, "real-world" emotional events, people demonstrated an immediacy bias in social-emotional comparisons, perceiving their own current or recent emotional reactions as more intense compared with others' emotional reactions to the same events. The events examined include crossing a scary bridge (study 1a), a national tragedy (study 1b), terrorist attacks (studies 2a and 3b), a natural disaster (study 2b), and a presidential election (study 3b). These perceived differences between one's own and others' emotions declined over time, as relatively immediate and recent emotions subsided, a pattern that people were not intuitively aware of (study 2c). This immediacy bias in social-emotional comparisons emerged for both explicit comparisons (studies 1a, 1b, and 3b), and for absolute judgments of emotional intensity (studies 2a, 2b, and 3a). Finally, the immediacy bias in social-emotional comparisons was reduced when people were reminded that emotional display norms might lead others' appearances to understate emotional intensity (studies 3a and 3b). Implications of these findings for social-emotional phenomena are discussed.

  8. Learning biases predict a word order universal.

    Science.gov (United States)

    Culbertson, Jennifer; Smolensky, Paul; Legendre, Géraldine

    2012-03-01

    How recurrent typological patterns, or universals, emerge from the extensive diversity found across the world's languages constitutes a central question for linguistics and cognitive science. Recent challenges to a fundamental assumption of generative linguistics-that universal properties of the human language acquisition faculty constrain the types of grammatical systems which can occur-suggest the need for new types of empirical evidence connecting typology to biases of learners. Using an artificial language learning paradigm in which adult subjects are exposed to a mix of grammatical systems (similar to a period of linguistic change), we show that learners' biases mirror a word-order universal, first proposed by Joseph Greenberg, which constrains typological patterns of adjective, numeral, and noun ordering. We briefly summarize the results of a probabilistic model of the hypothesized biases and their effect on learning, and discuss the broader implications of the results for current theories of the origins of cross-linguistic word-order preferences. Copyright © 2011 Elsevier B.V. All rights reserved.

  9. Managing Disagreement: A Defense of "Regime Bias"

    Science.gov (United States)

    Sabl, Andrew

    2011-02-01

    Stein Ringen's theory of democratic purpose cannot do the work expected of it. Ringen's own criteria oscillate between being too vague to be useful (i.e. "freedom") or, when specified more fully, conflicting, so that almost all democracies will seem to be potentially at cross-purposes with themselves rather than their purposes or sub-purposes being mutually reinforcing. This reflects a bigger and more theoretical problem. Disagreement about the purpose of democracy is built into democracy itself. The whole point of many (perhaps all) of our democratic institutions is to arrive at conditionally legitimate decisions in spite of such disagreement. So-called regime bias, i.e. the tendency to assess democracies according to the form and stability of their institutions rather than their results or their ability to serve certain purposes, does not in fact arise from bias. It arises on the contrary from a determination to avoid the bias inherent in giving some-inevitably partisan-ideals of what democracies should do pride of place over others in a scheme of measurement or evaluation. And even a regime-based definition of democracy must itself make simplifying assumptions that elide possible normative controversies over how the democratic game is best played. Vindicating one's preferred set of democratic ideals against alternatives is a completely legitimate enterprise and lends richness to debates within and across democracies. But it is an inherently ideological and political enterprise, not a neutral or scholarly one.

  10. Bias temperature instability for devices and circuits

    CERN Document Server

    2014-01-01

    This book provides a single-source reference to one of the more challenging reliability issues plaguing modern semiconductor technologies, negative bias temperature instability.  Readers will benefit from state-of-the art coverage of research in topics such as time dependent defect spectroscopy, anomalous defect behavior, stochastic modeling with additional metastable states, multiphonon theory, compact modeling with RC ladders and implications on device reliability and lifetime.  ·         Enables readers to understand and model negative bias temperature instability, with an emphasis on dynamics; ·         Includes coverage of DC vs. AC stress, duty factor dependence and bias dependence; ·         Explains time dependent defect spectroscopy, as a measurement method that operates on nanoscale MOSFETs; ·         Introduces new defect model for metastable defect states, nonradiative multiphonon theory and stochastic behavior.

  11. A basis for bias in geographical judgments.

    Science.gov (United States)

    Friedman, Alinda; Brown, Norman R; McGaffey, Aaron P

    2002-03-01

    To determine why North Americans tend to locate European cities south of North American cities at similar latitudes (Tversky, 1981), we had observers provide bearing estimates between cities in the U.S. and Europe. Earlier research using latitude estimates of these cities has indicated that each continent has several subjective regions (Friedman & Brown, 2000a). Participants judged cities from two subjectively northern regions (Milwaukee-Munich), two subjectively southern regions (Memphis-Lisbon), and the two "crossed" regions (Albuquerque-Geneva; Minneapolis-Rome). Estimates were biased only when cities from the subjectively northern regions of North America were paired with cities from the subjectively southern region of Europe. In contrast to the view that biases are derived from distorted or aligned map-like representations, the data provide evidence that the subjective representation of global geography is principally categorical. Biases in numerical location estimates of individual cities and in bearing estimates between city pairs are derived from plausible reasoning processes operating on the same categorical representations.

  12. Cognitive Reflection, Decision Biases, and Response Times

    Directory of Open Access Journals (Sweden)

    Carlos Alos-Ferrer

    2016-09-01

    Full Text Available We present novel evidence on decision times and personality traits in standard questions from the decision-making literature where responses are relatively slow (medians around half a minute or above. To this end, we measured decision times in a number of incentivized, framed items (decisions from description including the Cognitive Reflection Test, two additional questions following the same logic, and a number of classic questions used to study decision biases in probability judgments (base-rate neglect, the conjunction fallacy, and the ratio bias. All questions create a conflict between an intuitive process and more deliberative thinking. For each item, we then created a non-conflict version by either making the intuitive impulse correct (resulting in an alignment question, shutting it down (creating a neutral question, or making it dominant (creating a heuristic question. For CRT questions, the differences in decision times are as predicted by dual-process theories, with alignment and heuristic variants leading to faster responses and neutral questions to slower responses than the original, conflict questions. For decision biases (where responses are slower, evidence is mixed. To explore the possible influence of personality factors on both choices and decision times, we used standard personality scales including the Rational-Experiential Inventory and the Big Five, and used the mas controls in regression analysis.

  13. Cognitive Reflection, Decision Biases, and Response Times.

    Science.gov (United States)

    Alós-Ferrer, Carlos; Garagnani, Michele; Hügelschäfer, Sabine

    2016-01-01

    We present novel evidence on response times and personality traits in standard questions from the decision-making literature where responses are relatively slow (medians around half a minute or above). To this end, we measured response times in a number of incentivized, framed items (decisions from description) including the Cognitive Reflection Test, two additional questions following the same logic, and a number of classic questions used to study decision biases in probability judgments (base-rate neglect, the conjunction fallacy, and the ratio bias). All questions create a conflict between an intuitive process and more deliberative thinking. For each item, we then created a non-conflict version by either making the intuitive impulse correct (resulting in an alignment question), shutting it down (creating a neutral question), or making it dominant (creating a heuristic question). For CRT questions, the differences in response times are as predicted by dual-process theories, with alignment and heuristic variants leading to faster responses and neutral questions to slower responses than the original, conflict questions. For decision biases (where responses are slower), evidence is mixed. To explore the possible influence of personality factors on both choices and response times, we used standard personality scales including the Rational-Experiential Inventory and the Big Five, and used them as controls in regression analysis.

  14. Sampling bias in climate-conflict research

    Science.gov (United States)

    Adams, Courtland; Ide, Tobias; Barnett, Jon; Detges, Adrien

    2018-03-01

    Critics have argued that the evidence of an association between climate change and conflict is flawed because the research relies on a dependent variable sampling strategy1-4. Similarly, it has been hypothesized that convenience of access biases the sample of cases studied (the `streetlight effect'5). This also gives rise to claims that the climate-conflict literature stigmatizes some places as being more `naturally' violent6-8. Yet there has been no proof of such sampling patterns. Here we test whether climate-conflict research is based on such a biased sample through a systematic review of the literature. We demonstrate that research on climate change and violent conflict suffers from a streetlight effect. Further, studies which focus on a small number of cases in particular are strongly informed by cases where there has been conflict, do not sample on the independent variables (climate impact or risk), and hence tend to find some association between these two variables. These biases mean that research on climate change and conflict primarily focuses on a few accessible regions, overstates the links between both phenomena and cannot explain peaceful outcomes from climate change. This could result in maladaptive responses in those places that are stigmatized as being inherently more prone to climate-induced violence.

  15. Perceptive biases in major depressive episode.

    Directory of Open Access Journals (Sweden)

    Marine Naudin

    Full Text Available INTRODUCTION: Alterations in emotional processing occur during a major depressive episode (MDE, and olfaction and facial expressions have implications in emotional and social interactions. To gain a better understanding of these processes, we characterized the perceptive sensorial biases, potential links, and potential remission after antidepressant treatment of MDE. METHODS: We recruited 22 patients with acute MDE, both before and after three months of antidepressant treatment, and 41 healthy volunteers matched by age and smoking status. The participants underwent a clinical assessment (Mini International Neuropsychiatry Interview, Montgomery-Åsberg Depression Rating Scale, State-Trait Anxiety Inventory, Physical and Social Anhedonia scales, Pleasure-Displeasure Scale, an olfactory evaluation (hedonic aspect, familiarity and emotional impact of odors, and a computerized Facial Affect Recognition task. RESULTS: MDE was associated with an olfactory bias concerning hedonic and emotional aspects, including negative olfactory alliesthesia (unpleasant odorants perceived as more unpleasant, facial emotion expression recognition (happy facial expressions, and in part olfactory anhedonia (pleasant odorants perceived as less pleasant. In addition, the results revealed that these impairments represent state markers of MDE, suggesting that the patients recovered the same sensory processing as healthy subjects after antidepressant treatment. DISCUSSION: This study demonstrated that MDE is associated with negative biases toward olfactory perception and the recognition of facial emotional expressions. The link between these two sensory parameters suggests common underlying processes.

  16. Sampling of temporal networks: Methods and biases

    Science.gov (United States)

    Rocha, Luis E. C.; Masuda, Naoki; Holme, Petter

    2017-11-01

    Temporal networks have been increasingly used to model a diversity of systems that evolve in time; for example, human contact structures over which dynamic processes such as epidemics take place. A fundamental aspect of real-life networks is that they are sampled within temporal and spatial frames. Furthermore, one might wish to subsample networks to reduce their size for better visualization or to perform computationally intensive simulations. The sampling method may affect the network structure and thus caution is necessary to generalize results based on samples. In this paper, we study four sampling strategies applied to a variety of real-life temporal networks. We quantify the biases generated by each sampling strategy on a number of relevant statistics such as link activity, temporal paths and epidemic spread. We find that some biases are common in a variety of networks and statistics, but one strategy, uniform sampling of nodes, shows improved performance in most scenarios. Given the particularities of temporal network data and the variety of network structures, we recommend that the choice of sampling methods be problem oriented to minimize the potential biases for the specific research questions on hand. Our results help researchers to better design network data collection protocols and to understand the limitations of sampled temporal network data.

  17. Cooperative ethylene receptor signaling

    OpenAIRE

    Liu, Qian; Wen, Chi-Kuang

    2012-01-01

    The gaseous plant hormone ethylene is perceived by a family of five ethylene receptor members in the dicotyledonous model plant Arabidopsis. Genetic and biochemical studies suggest that the ethylene response is suppressed by ethylene receptor complexes, but the biochemical nature of the receptor signal is unknown. Without appropriate biochemical measures to trace the ethylene receptor signal and quantify the signal strength, the biological significance of the modulation of ethylene responses ...

  18. Biases in Drosophila melanogaster protein trap screens

    Directory of Open Access Journals (Sweden)

    Müller Ilka

    2009-05-01

    Full Text Available Abstract Background The ability to localise or follow endogenous proteins in real time in vivo is of tremendous utility for cell biology or systems biology studies. Protein trap screens utilise the random genomic insertion of a transposon-borne artificial reporter exon (e.g. encoding the green fluorescent protein, GFP into an intron of an endogenous gene to generate a fluorescent fusion protein. Despite recent efforts aimed at achieving comprehensive coverage of the genes encoded in the Drosophila genome, the repertoire of genes that yield protein traps is still small. Results We analysed the collection of available protein trap lines in Drosophila melanogaster and identified potential biases that are likely to restrict genome coverage in protein trap screens. The protein trap screens investigated here primarily used P-element vectors and thus exhibit some of the same positional biases associated with this transposon that are evident from the comprehensive Drosophila Gene Disruption Project. We further found that protein trap target genes usually exhibit broad and persistent expression during embryonic development, which is likely to facilitate better detection. In addition, we investigated the likely influence of the GFP exon on host protein structure and found that protein trap insertions have a significant bias for exon-exon boundaries that encode disordered protein regions. 38.8% of GFP insertions land in disordered protein regions compared with only 23.4% in the case of non-trapping P-element insertions landing in coding sequence introns (p -4. Interestingly, even in cases where protein domains are predicted, protein trap insertions frequently occur in regions encoding surface exposed areas that are likely to be functionally neutral. Considering the various biases observed, we predict that less than one third of intron-containing genes are likely to be amenable to trapping by the existing methods. Conclusion Our analyses suggest that the

  19. Relative equilibrium plot improves graphical analysis and allows bias correction of SUVR in quantitative [11C]PiB PET studies

    OpenAIRE

    Zhou, Yun; Sojkova, Jitka; Resnick, Susan M.; Wong, Dean F.

    2012-01-01

    Both the standardized uptake value ratio (SUVR) and the Logan plot result in biased distribution volume ratios (DVR) in ligand-receptor dynamic PET studies. The objective of this study is to use a recently developed relative equilibrium-based graphical plot (RE plot) method to improve and simplify the two commonly used methods for quantification of [11C]PiB PET.

  20. Dual-electrode biasing experiments in KT-5C device

    International Nuclear Information System (INIS)

    Yu Yi; Lu Ronghua; Wang Chen; Pan Geshen; Wen Yizhi; Yu Changxuan; Ma Jinxiu; Wan Shude; Liu Wandong

    2005-01-01

    Based on the single biasing electrode experiments to optimize the confinement of plasma in the device of KT-5C tokamak, dual-biasing electrodes were inserted into the KT5C plasma for the first time to explore the enhancement of the effects of biasing and the mechanisms of the biasing. By means of applying different combinations of biasing voltages to the dual electrodes, the changes in E r , which is the key factor for boosting up the Er x B flow shear, were observed. The time evolution showed the inner electrode played a major role in dual-biasing, for it always drew a larger current than the outer one. The outer electrode made little influence. It turned out that the dual-biasing electrodes were as effective as a single one, in improving plasma confinement, for the mechanism of biasing was essentially an edge effect. (author)

  1. Impact of Continued Biased Disenrollment from the Medic...

    Data.gov (United States)

    U.S. Department of Health & Human Services — Impact of Continued Biased Disenrollment from the Medicare Advantage Program to Fee-for-Service As reported in Impact of Continued Biased Disenrollment from the...

  2. Bias-Correction in Vector Autoregressive Models: A Simulation Study

    Directory of Open Access Journals (Sweden)

    Tom Engsted

    2014-03-01

    Full Text Available We analyze the properties of various methods for bias-correcting parameter estimates in both stationary and non-stationary vector autoregressive models. First, we show that two analytical bias formulas from the existing literature are in fact identical. Next, based on a detailed simulation study, we show that when the model is stationary this simple bias formula compares very favorably to bootstrap bias-correction, both in terms of bias and mean squared error. In non-stationary models, the analytical bias formula performs noticeably worse than bootstrapping. Both methods yield a notable improvement over ordinary least squares. We pay special attention to the risk of pushing an otherwise stationary model into the non-stationary region of the parameter space when correcting for bias. Finally, we consider a recently proposed reduced-bias weighted least squares estimator, and we find that it compares very favorably in non-stationary models.

  3. Codon usage bias analysis for the coding sequences of Camellia ...

    African Journals Online (AJOL)

    sunny t

    2016-02-24

    Feb 24, 2016 ... suggested that codon usage bias is driven by selection, particularly for .... For example, as mentioned above, highly expressed genes tend to use fewer ... directional codon bias measure effective number of codons (ENc) was ...

  4. No evidence for a bone phenotype in GPRC6A knockout mice under normal physiological conditions

    DEFF Research Database (Denmark)

    Wellendorph, Petrine; Johansen, Lars Dan; Jensen, Anders Asbjørn

    2009-01-01

    GPRC6A is a seven transmembrane receptor mediating signaling by a wide range of L-alpha-amino-acids, a signaling augmented by the divalent cations Ca2+ and Mg2+. GPRC6A transcripts are detected in numerous mammalian tissues, but the physiological role of the receptor is thus far elusive. Analogou...

  5. Molecular characterization of oxysterol binding to the Epstein-Barr virus-induced gene 2 (GPR183)

    DEFF Research Database (Denmark)

    Benned-Jensen, Tau; Norn, Christoffer; Laurent, Stephane

    2012-01-01

    , the family of G protein-coupled seven transmembrane-spanning receptors (7TM receptors) was added to this group. Specifically, the Epstein-Barr virus-induced gene 2 (EBI2 or GPR183) was shown to be activated by several oxysterols, most potently by 7α,25-dihydroxycholesterol (7α,25-OHC). Nothing is known about...

  6. InterProScan Result: FS856416 [KAIKOcDNA[Archive

    Lifescience Database Archive (English)

    Full Text Available FS856416 FS856416_5_ORF1 8BC932287F58E2D2 PANTHER PTHR21229 LUNG SEVEN TRANSMEMBRAN...E RECEPTOR 3.7e-48 T IPR009637 Transmembrane receptor, eukaryota Cellular Component: integral to membrane (GO:0016021) ...

  7. InterProScan Result: FS763011 [KAIKOcDNA[Archive

    Lifescience Database Archive (English)

    Full Text Available FS763011 FS763011_3_ORF1 ADA83816196D1572 PANTHER PTHR21229 LUNG SEVEN TRANSMEMBRAN...E RECEPTOR 1.2e-07 T IPR009637 Transmembrane receptor, eukaryota Cellular Component: integral to membrane (GO:0016021) ...

  8. InterProScan Result: FS765894 [KAIKOcDNA[Archive

    Lifescience Database Archive (English)

    Full Text Available FS765894 FS765894_3_ORF2 2218C53708677A45 PANTHER PTHR21229 LUNG SEVEN TRANSMEMBRAN...E RECEPTOR 7.9e-11 T IPR009637 Transmembrane receptor, eukaryota Cellular Component: integral to membrane (GO:0016021) ...

  9. Stimulus-driven attention, threat bias, and sad bias in youth with a history of an anxiety disorder or depression

    Science.gov (United States)

    Sylvester, Chad M.; Hudziak, James J.; Gaffrey, Michael S.; Barch, Deanna M.; Luby, Joan L.

    2015-01-01

    Attention biases towards threatening and sad stimuli are associated with pediatric anxiety and depression, respectively. The basic cognitive mechanisms associated with attention biases in youth, however, remain unclear. Here, we tested the hypothesis that threat bias (selective attention for threatening versus neutral stimuli) but not sad bias relies on stimulus-driven attention. We collected measures of stimulus-driven attention, threat bias, sad bias, and current clinical symptoms in youth with a history of an anxiety disorder and/or depression (ANX/DEP; n=40) as well as healthy controls (HC; n=33). Stimulus-driven attention was measured with a non-emotional spatial orienting task, while threat bias and sad bias were measured at a short time interval (150 ms) with a spatial orienting task using emotional faces and at a longer time interval (500 ms) using a dot-probe task. In ANX/DEP but not HC, early attention bias towards threat was negatively correlated with later attention bias to threat, suggesting that early threat vigilance was associated with later threat avoidance. Across all subjects, stimulus-driven orienting was not correlated with early threat bias but was negatively correlated with later threat bias, indicating that rapid stimulus-driven orienting is linked to later threat avoidance. No parallel relationships were detected for sad bias. Current symptoms of depression but not anxiety were related to decreased stimulus-driven attention. Together, these results are consistent with the hypothesis that threat bias but not sad bias relies on stimulus-driven attention. These results inform the design of attention bias modification programs that aim to reverse threat biases and reduce symptoms associated with pediatric anxiety and depression. PMID:25702927

  10. Stimulus-Driven Attention, Threat Bias, and Sad Bias in Youth with a History of an Anxiety Disorder or Depression.

    Science.gov (United States)

    Sylvester, Chad M; Hudziak, James J; Gaffrey, Michael S; Barch, Deanna M; Luby, Joan L

    2016-02-01

    Attention biases towards threatening and sad stimuli are associated with pediatric anxiety and depression, respectively. The basic cognitive mechanisms associated with attention biases in youth, however, remain unclear. Here, we tested the hypothesis that threat bias (selective attention for threatening versus neutral stimuli) but not sad bias relies on stimulus-driven attention. We collected measures of stimulus-driven attention, threat bias, sad bias, and current clinical symptoms in youth with a history of an anxiety disorder and/or depression (ANX/DEP; n = 40) as well as healthy controls (HC; n = 33). Stimulus-driven attention was measured with a non-emotional spatial orienting task, while threat bias and sad bias were measured at a short time interval (150 ms) with a spatial orienting task using emotional faces and at a longer time interval (500 ms) using a dot-probe task. In ANX/DEP but not HC, early attention bias towards threat was negatively correlated with later attention bias to threat, suggesting that early threat vigilance was associated with later threat avoidance. Across all subjects, stimulus-driven orienting was not correlated with early threat bias but was negatively correlated with later threat bias, indicating that rapid stimulus-driven orienting is linked to later threat avoidance. No parallel relationships were detected for sad bias. Current symptoms of depression but not anxiety were related to decreased stimulus-driven attention. Together, these results are consistent with the hypothesis that threat bias but not sad bias relies on stimulus-driven attention. These results inform the design of attention bias modification programs that aim to reverse threat biases and reduce symptoms associated with pediatric anxiety and depression.

  11. Attention, interpretation, and memory biases in subclinical depression: a proof-of-principle test of the combined cognitive biases hypothesis.

    Science.gov (United States)

    Everaert, Jonas; Duyck, Wouter; Koster, Ernst H W

    2014-04-01

    Emotional biases in attention, interpretation, and memory are viewed as important cognitive processes underlying symptoms of depression. To date, there is a limited understanding of the interplay among these processing biases. This study tested the dependence of memory on depression-related biases in attention and interpretation. Subclinically depressed and nondepressed participants completed a computerized version of the scrambled sentences test (measuring interpretation bias) while their eye movements were recorded (measuring attention bias). This task was followed by an incidental free recall test of previously constructed interpretations (measuring memory bias). Path analysis revealed a good fit for the model in which selective orienting of attention was associated with interpretation bias, which in turn was associated with a congruent bias in memory. Also, a good fit was observed for a path model in which biases in the maintenance of attention and interpretation were associated with memory bias. Both path models attained a superior fit compared with path models without the theorized functional relations among processing biases. These findings enhance understanding of how mechanisms of attention and interpretation regulate what is remembered. As such, they offer support for the combined cognitive biases hypothesis or the notion that emotionally biased cognitive processes are not isolated mechanisms but instead influence each other. Implications for theoretical models and emotion regulation across the spectrum of depressive symptoms are discussed.

  12. Simulation of HPIB propagation in biased charge collector

    International Nuclear Information System (INIS)

    Li Hongyu; Qiu Aici

    2004-01-01

    A 2.5D PIC simulation using KARAT code for inner charge propagation within biased charge collector for measuring HPIB is presented. The simulation results indicate that the charges were neutralized but the current non-neutralized in the biased charge collector. The influence of ions collected vs biased voltage of the collector was also simulated. -800 V biased voltage can meet the measurement of 500 keV HPIB, and this is consistent with the experimental results

  13. On the Borders of Harmful and Helpful Beauty Biases

    OpenAIRE

    Maria Agthe; Maria Strobel; Matthias Spörrle; Michaela Pfundmair; Jon K. Maner

    2016-01-01

    Research with European Caucasian samples demonstrates that attractiveness-based biases in social evaluation depend on the constellation of the sex of the evaluator and the sex of the target: Whereas people generally show positive biases toward attractive opposite-sex persons, they show less positive or even negative biases toward attractive same-sex persons. By examining these biases both within and between different ethnicities, the current studies provide new evidence for both the generaliz...

  14. Bias versus bias: harnessing hindsight to reveal paranormal belief change beyond demand characteristics.

    Science.gov (United States)

    Kane, Michael J; Core, Tammy J; Hunt, R Reed

    2010-04-01

    Psychological change is difficult to assess, in part because self-reported beliefs and attitudes may be biased or distorted. The present study probed belief change, in an educational context, by using the hindsight bias to counter another bias that generally plagues assessment of subjective change. Although research has indicated that skepticism courses reduce paranormal beliefs, those findings may reflect demand characteristics (biases toward desired, skeptical responses). Our hindsight-bias procedure circumvented demand by asking students, following semester-long skepticism (and control) courses, to recall their precourse levels of paranormal belief. People typically remember themselves as previously thinking, believing, and acting as they do now, so current skepticism should provoke false recollections of previous skepticism. Given true belief change, therefore, skepticism students should have remembered themselves as having been more skeptical than they were. They did, at least about paranormal topics that were covered most extensively in the course. Our findings thus show hindsight to be useful in evaluating cognitive change beyond demand characteristics.

  15. Cognitive bias in action: evidence for a reciprocal relation between confirmation bias and fear in children.

    Science.gov (United States)

    Remmerswaal, Danielle; Huijding, Jorg; Bouwmeester, Samantha; Brouwer, Marlies; Muris, Peter

    2014-03-01

    Some cognitive models propose that information processing biases and fear are reciprocally related. This idea has never been formally tested. Therefore, this study investigated the existence of a vicious circle by which confirmation bias and fear exacerbate each other. One-hundred-and-seventy-one school children (8-13 years) were first provided with threatening, ambiguous, or positive information about an unknown animal. Then they completed a computerized information search task during which they could collect additional (negative, positive, or neutral) information about the novel animal. Because fear levels were repeatedly assessed during the task, it was possible to examine the reciprocal relationship between confirmation bias and fear. A reciprocal relation of mutual reinforcement was found between confirmation bias and fear over the course of the experiment: increases in fear predicted subsequent increases in the search for negative information, and increases in the search for negative information further enhanced fear on a later point-in-time. In addition, the initial information given about the animals successfully induced diverging fear levels in the children, and determined their first inclination to search for additional information. As this study employed a community sample of primary school children, future research should test whether these results can be generalized to clinically anxious youth. These findings provide first support for the notion that fearful individuals may become trapped in a vicious circle in which fear and a fear-related confirmation bias mutually strengthen each other, thereby maintaining the anxiety pathology. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Development of Heuristic Bias Detection in Elementary School

    Science.gov (United States)

    De Neys, Wim; Feremans, Vicky

    2013-01-01

    Although human reasoning is often biased by intuitive heuristics, recent studies have shown that adults and adolescents detect the biased nature of their judgments. The present study focused on the development of this critical bias sensitivity by examining the detection skills of young children in elementary school. Third and 6th graders were…

  17. Product Aggregation Bias as a Specification Error in Demand Systems

    OpenAIRE

    George C. Davis

    1997-01-01

    Inherent in all demand studies is some form of product aggregation which can lead to product aggregation bias. This article develops a simple procedure for incorporating product aggregation bias in demand systems that permits testing of product aggregation bias with a standard likelihood ratio test. An empirical illustration of the procedure demonstrates the importance of proper product aggregation. Copyright 1997, Oxford University Press.

  18. Dwalingen in de methodologie. II. Bias door vragenlijsten

    DEFF Research Database (Denmark)

    Pouwer, F; Van Der Ploeg, Henk M; Bramsen, I

    1998-01-01

    Some characteristics of self-report questionnaires can result in bias in responding. When a test item or a questionnaire is biased, the observed scores form an imprecise measurement of reality as a consequence of systematic errors of measurement. Causes of such bias are: unclear instructions, vague...

  19. Bias in Examination Test Banks that Accompany Cost Accounting Texts.

    Science.gov (United States)

    Clute, Ronald C.; McGrail, George R.

    1989-01-01

    Eight text banks that accompany cost accounting textbooks were evaluated for the presence of bias in the distribution of correct responses. All but one were found to have considerable bias, and three of eight were found to have significant choice bias. (SK)

  20. Imaging the neural effects of cognitive bias modification training

    NARCIS (Netherlands)

    Wiers, C.E.; Wiers, R.W.

    Cognitive bias modification (CBM) was first developed as an experimental tool to examine the causal role of cognitive biases, and later developed into complementary interventions in experimental psychopathology research. CBM involves the "re-training" of implicit biases by means of multiple trials

  1. A Principal Components Analysis of Dynamic Spatial Memory Biases

    Science.gov (United States)

    Motes, Michael A.; Hubbard, Timothy L.; Courtney, Jon R.; Rypma, Bart

    2008-01-01

    Research has shown that spatial memory for moving targets is often biased in the direction of implied momentum and implied gravity, suggesting that representations of the subjective experiences of these physical principles contribute to such biases. The present study examined the association between these spatial memory biases. Observers viewed…

  2. Whiteliness and Institutional Racism: Hiding behind (Un)Conscious Bias

    Science.gov (United States)

    Tate, Shirley Anne; Page, Damien

    2018-01-01

    'Unconscious bias happens by our brains making incredibly quick judgements and assessments without us realising. Biases are influenced by background, cultural environment and experiences and we may not be aware of these views and opinions, or of their full impact and implications. This article opposes this point of view by arguing that bias is not…

  3. A machine learning model with human cognitive biases capable of learning from small and biased datasets.

    Science.gov (United States)

    Taniguchi, Hidetaka; Sato, Hiroshi; Shirakawa, Tomohiro

    2018-05-09

    Human learners can generalize a new concept from a small number of samples. In contrast, conventional machine learning methods require large amounts of data to address the same types of problems. Humans have cognitive biases that promote fast learning. Here, we developed a method to reduce the gap between human beings and machines in this type of inference by utilizing cognitive biases. We implemented a human cognitive model into machine learning algorithms and compared their performance with the currently most popular methods, naïve Bayes, support vector machine, neural networks, logistic regression and random forests. We focused on the task of spam classification, which has been studied for a long time in the field of machine learning and often requires a large amount of data to obtain high accuracy. Our models achieved superior performance with small and biased samples in comparison with other representative machine learning methods.

  4. Bias-limited extraction of cosmological parameters

    Energy Technology Data Exchange (ETDEWEB)

    Shimon, Meir; Itzhaki, Nissan; Rephaeli, Yoel, E-mail: meirs@wise.tau.ac.il, E-mail: nitzhaki@post.tau.ac.il, E-mail: yoelr@wise.tau.ac.il [School of Physics and Astronomy, Tel Aviv University, Tel Aviv 69978 (Israel)

    2013-03-01

    It is known that modeling uncertainties and astrophysical foregrounds can potentially introduce appreciable bias in the deduced values of cosmological parameters. While it is commonly assumed that these uncertainties will be accounted for to a sufficient level of precision, the level of bias has not been properly quantified in most cases of interest. We show that the requirement that the bias in derived values of cosmological parameters does not surpass nominal statistical error, translates into a maximal level of overall error O(N{sup −½}) on |ΔP(k)|/P(k) and |ΔC{sub l}|/C{sub l}, where P(k), C{sub l}, and N are the matter power spectrum, angular power spectrum, and number of (independent Fourier) modes at a given scale l or k probed by the cosmological survey, respectively. This required level has important consequences on the precision with which cosmological parameters are hoped to be determined by future surveys: in virtually all ongoing and near future surveys N typically falls in the range 10{sup 6}−10{sup 9}, implying that the required overall theoretical modeling and numerical precision is already very high. Future redshifted-21-cm observations, projected to sample ∼ 10{sup 14} modes, will require knowledge of the matter power spectrum to a fantastic 10{sup −7} precision level. We conclude that realizing the expected potential of future cosmological surveys, which aim at detecting 10{sup 6}−10{sup 14} modes, sets the formidable challenge of reducing the overall level of uncertainty to 10{sup −3}−10{sup −7}.

  5. Heuristics and bias in rectal surgery.

    Science.gov (United States)

    MacDermid, Ewan; Young, Christopher J; Moug, Susan J; Anderson, Robert G; Shepherd, Heather L

    2017-08-01

    Deciding to defunction after anterior resection can be difficult, requiring cognitive tools or heuristics. From our previous work, increasing age and risk-taking propensity were identified as heuristic biases for surgeons in Australia and New Zealand (CSSANZ), and inversely proportional to the likelihood of creating defunctioning stomas. We aimed to assess these factors for colorectal surgeons in the British Isles, and identify other potential biases. The Association of Coloproctology of Great Britain and Ireland (ACPGBI) was invited to complete an online survey. Questions included demographics, risk-taking propensity, sensitivity to professional criticism, self-perception of anastomotic leak rate and propensity for creating defunctioning stomas. Chi-squared testing was used to assess differences between ACPGBI and CSSANZ respondents. Multiple regression analysis identified independent surgeon predictors of stoma formation. One hundred fifty (19.2%) eligible members of the ACPGBI replied. Demographics between ACPGBI and CSSANZ groups were well-matched. Significantly more ACPGBI surgeons admitted to anastomotic leak in the last year (p < 0.001). ACPGBI surgeon age over 50 (p = 0.02), higher risk-taking propensity across several domains (p = 0.044), self-belief in a lower-than-average anastomotic leak rate (p = 0.02) and belief that the average risk of leak after anterior resection is 8% or lower (p = 0.007) were all independent predictors of less frequent stoma formation. Sensitivity to criticism from colleagues was not a predictor of stoma formation. Unrecognised surgeon factors including age, everyday risk-taking, self-belief in surgical ability and lower probability bias of anastomotic leak appear to exert an effect on decision-making in rectal surgery.

  6. Hybrid biasing approaches for global variance reduction

    International Nuclear Information System (INIS)

    Wu, Zeyun; Abdel-Khalik, Hany S.

    2013-01-01

    A new variant of Monte Carlo—deterministic (DT) hybrid variance reduction approach based on Gaussian process theory is presented for accelerating convergence of Monte Carlo simulation and compared with Forward-Weighted Consistent Adjoint Driven Importance Sampling (FW-CADIS) approach implemented in the SCALE package from Oak Ridge National Laboratory. The new approach, denoted the Gaussian process approach, treats the responses of interest as normally distributed random processes. The Gaussian process approach improves the selection of the weight windows of simulated particles by identifying a subspace that captures the dominant sources of statistical response variations. Like the FW-CADIS approach, the Gaussian process approach utilizes particle importance maps obtained from deterministic adjoint models to derive weight window biasing. In contrast to the FW-CADIS approach, the Gaussian process approach identifies the response correlations (via a covariance matrix) and employs them to reduce the computational overhead required for global variance reduction (GVR) purpose. The effective rank of the covariance matrix identifies the minimum number of uncorrelated pseudo responses, which are employed to bias simulated particles. Numerical experiments, serving as a proof of principle, are presented to compare the Gaussian process and FW-CADIS approaches in terms of the global reduction in standard deviation of the estimated responses. - Highlights: ► Hybrid Monte Carlo Deterministic Method based on Gaussian Process Model is introduced. ► Method employs deterministic model to calculate responses correlations. ► Method employs correlations to bias Monte Carlo transport. ► Method compared to FW-CADIS methodology in SCALE code. ► An order of magnitude speed up is achieved for a PWR core model.

  7. Does neurocognitive function affect cognitive bias toward an emotional stimulus? Association between general attentional ability and attentional bias toward threat

    OpenAIRE

    Hakamata, Yuko; Matsui, Mie; Tagaya, Hirokuni

    2014-01-01

    Background: Although poorer cognitive performance has been found to be associated with anxiety, it remains unclear whether neurocognitive function affects biased cognitive processing toward emotional information. We investigated whether general cognitive function evaluated with a standard neuropsychological test predicts biased cognition, focusing on attentional bias toward threat. Methods: One hundred and five healthy young adults completed a dot-probe task measuring attentional bias and ...

  8. Conceptual and methodological biases in network models.

    Science.gov (United States)

    Lamm, Ehud

    2009-10-01

    Many natural and biological phenomena can be depicted as networks. Theoretical and empirical analyses of networks have become prevalent. I discuss theoretical biases involved in the delineation of biological networks. The network perspective is shown to dissolve the distinction between regulatory architecture and regulatory state, consistent with the theoretical impossibility of distinguishing a priori between "program" and "data." The evolutionary significance of the dynamics of trans-generational and interorganism regulatory networks is explored and implications are presented for understanding the evolution of the biological categories development-heredity, plasticity-evolvability, and epigenetic-genetic.

  9. Biases in cold fusion data; and reply

    International Nuclear Information System (INIS)

    Freedman, Stuart; Krakauer, Daniel; Jones, S.E.; Decker, D.L.; Tolley, H.D.

    1990-01-01

    These two letters represent a criticism of a claim to have observed ''cold'' nuclear fusion and the original scientists' rebuttal of the claims against them. The first authors suggest that data presented has a peculiar characteristic, which, they claim, indicates a systematic bias in the data collection process, and thus calls the claimed observation into dispute. In reply, the original workers list a huge range of checks they made, before and after receiving the criticism, making allowances for all sorts of external parameters capable of affecting their results. (UK)

  10. Gender Bias and Child Labor in LDCs

    OpenAIRE

    Alok Kumar; Emma Underhill

    2014-01-01

    Empirical evidence suggests that girls work more than boys as child labor. In this paper, we develop a model to analyze the causes and consequences of the gender differentials in child labor. In particular, we analyze the effects of gender bias on child labor. We find that when parents can give strictly positive bequests to both boys and girls, son preference on its own does not lead to gender differential in child labor. Only when parents cannot give bequests, girls work more than boys as ch...

  11. Leveraging position bias to improve peer recommendation.

    Directory of Open Access Journals (Sweden)

    Kristina Lerman

    Full Text Available With the advent of social media and peer production, the amount of new online content has grown dramatically. To identify interesting items in the vast stream of new content, providers must rely on peer recommendation to aggregate opinions of their many users. Due to human cognitive biases, the presentation order strongly affects how people allocate attention to the available content. Moreover, we can manipulate attention through the presentation order of items to change the way peer recommendation works. We experimentally evaluate this effect using Amazon Mechanical Turk. We find that different policies for ordering content can steer user attention so as to improve the outcomes of peer recommendation.

  12. Biases in Visual, Auditory, and Audiovisual Perception of Space.

    Directory of Open Access Journals (Sweden)

    Brian Odegaard

    2015-12-01

    Full Text Available Localization of objects and events in the environment is critical for survival, as many perceptual and motor tasks rely on estimation of spatial location. Therefore, it seems reasonable to assume that spatial localizations should generally be accurate. Curiously, some previous studies have reported biases in visual and auditory localizations, but these studies have used small sample sizes and the results have been mixed. Therefore, it is not clear (1 if the reported biases in localization responses are real (or due to outliers, sampling bias, or other factors, and (2 whether these putative biases reflect a bias in sensory representations of space or a priori expectations (which may be due to the experimental setup, instructions, or distribution of stimuli. Here, to address these questions, a dataset of unprecedented size (obtained from 384 observers was analyzed to examine presence, direction, and magnitude of sensory biases, and quantitative computational modeling was used to probe the underlying mechanism(s driving these effects. Data revealed that, on average, observers were biased towards the center when localizing visual stimuli, and biased towards the periphery when localizing auditory stimuli. Moreover, quantitative analysis using a Bayesian Causal Inference framework suggests that while pre-existing spatial biases for central locations exert some influence, biases in the sensory representations of both visual and auditory space are necessary to fully explain the behavioral data. How are these opposing visual and auditory biases reconciled in conditions in which both auditory and visual stimuli are produced by a single event? Potentially, the bias in one modality could dominate, or the biases could interact/cancel out. The data revealed that when integration occurred in these conditions, the visual bias dominated, but the magnitude of this bias was reduced compared to unisensory conditions. Therefore, multisensory integration not only

  13. Biases in Visual, Auditory, and Audiovisual Perception of Space

    Science.gov (United States)

    Odegaard, Brian; Wozny, David R.; Shams, Ladan

    2015-01-01

    Localization of objects and events in the environment is critical for survival, as many perceptual and motor tasks rely on estimation of spatial location. Therefore, it seems reasonable to assume that spatial localizations should generally be accurate. Curiously, some previous studies have reported biases in visual and auditory localizations, but these studies have used small sample sizes and the results have been mixed. Therefore, it is not clear (1) if the reported biases in localization responses are real (or due to outliers, sampling bias, or other factors), and (2) whether these putative biases reflect a bias in sensory representations of space or a priori expectations (which may be due to the experimental setup, instructions, or distribution of stimuli). Here, to address these questions, a dataset of unprecedented size (obtained from 384 observers) was analyzed to examine presence, direction, and magnitude of sensory biases, and quantitative computational modeling was used to probe the underlying mechanism(s) driving these effects. Data revealed that, on average, observers were biased towards the center when localizing visual stimuli, and biased towards the periphery when localizing auditory stimuli. Moreover, quantitative analysis using a Bayesian Causal Inference framework suggests that while pre-existing spatial biases for central locations exert some influence, biases in the sensory representations of both visual and auditory space are necessary to fully explain the behavioral data. How are these opposing visual and auditory biases reconciled in conditions in which both auditory and visual stimuli are produced by a single event? Potentially, the bias in one modality could dominate, or the biases could interact/cancel out. The data revealed that when integration occurred in these conditions, the visual bias dominated, but the magnitude of this bias was reduced compared to unisensory conditions. Therefore, multisensory integration not only improves the

  14. The immitigable nature of assembly bias: the impact of halo definition on assembly bias

    Science.gov (United States)

    Villarreal, Antonio S.; Zentner, Andrew R.; Mao, Yao-Yuan; Purcell, Chris W.; van den Bosch, Frank C.; Diemer, Benedikt; Lange, Johannes U.; Wang, Kuan; Campbell, Duncan

    2017-11-01

    Dark matter halo clustering depends not only on halo mass, but also on other properties such as concentration and shape. This phenomenon is known broadly as assembly bias. We explore the dependence of assembly bias on halo definition, parametrized by spherical overdensity parameter, Δ. We summarize the strength of concentration-, shape-, and spin-dependent halo clustering as a function of halo mass and halo definition. Concentration-dependent clustering depends strongly on mass at all Δ. For conventional halo definitions (Δ ∼ 200 - 600 m), concentration-dependent clustering at low mass is driven by a population of haloes that is altered through interactions with neighbouring haloes. Concentration-dependent clustering can be greatly reduced through a mass-dependent halo definition with Δ ∼ 20 - 40 m for haloes with M200 m ≲ 1012 h-1M⊙. Smaller Δ implies larger radii and mitigates assembly bias at low mass by subsuming altered, so-called backsplash haloes into now larger host haloes. At higher masses (M200 m ≳ 1013 h-1M⊙) larger overdensities, Δ ≳ 600 m, are necessary. Shape- and spin-dependent clustering are significant for all halo definitions that we explore and exhibit a relatively weaker mass dependence. Generally, both the strength and the sense of assembly bias depend on halo definition, varying significantly even among common definitions. We identify no halo definition that mitigates all manifestations of assembly bias. A halo definition that mitigates assembly bias based on one halo property (e.g. concentration) must be mass dependent. The halo definitions that best mitigate concentration-dependent halo clustering do not coincide with the expected average splashback radii at fixed halo mass.

  15. Monte Carlo shielding analyses using an automated biasing procedure

    International Nuclear Information System (INIS)

    Tang, J.S.; Hoffman, T.J.

    1988-01-01

    A systematic and automated approach for biasing Monte Carlo shielding calculations is described. In particular, adjoint fluxes from a one-dimensional discrete ordinates calculation are used to generate biasing parameters for a Monte Carlo calculation. The entire procedure of adjoint calculation, biasing parameters generation, and Monte Carlo calculation has been automated. The automated biasing procedure has been applied to several realistic deep-penetration shipping cask problems. The results obtained for neutron and gamma-ray transport indicate that with the automated biasing procedure Monte Carlo shielding calculations of spent-fuel casks can be easily performed with minimum effort and that accurate results can be obtained at reasonable computing cost

  16. Recent Advances in Attention Bias Modification for Substance Addictions

    Directory of Open Access Journals (Sweden)

    Melvyn Weibin Zhang

    2018-04-01

    Full Text Available Research on attentional bias modification has increased since 2014. A recent meta-analysis demonstrates evidence for bias modification for substance disorders, including alcohol and tobacco use disorders. Several pharmacological trials have shown that pharmacological agents can attenuate and modify such attentional bias. The pharmacological trials that have appeared to date have produced mixed results, which has clinical implications. Developments in Internet and mobile technologies have transformed how attention bias modification is currently being achieved. There remains great potential for further research that examines the efficacy of technology-aided attention bias interventions.

  17. GABA receptor imaging

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jong Doo [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2007-04-15

    GABA is primary an inhibitory neurotransmitter that is localized in inhibitory interneurons. GABA is released from presynaptic terminals and functions by binding to GABA receptors. There are two types of GABA receptors, GABA{sub A}-receptor that allows chloride to pass through a ligand gated ion channel and GABA{sub B}-receptor that uses G-proteins for signaling. The GABA{sub A}-receptor has a GABA binding site as well as a benzodiazepine binding sites, which modulate GABA{sub A}-receptor function. Benzodiazepine GABAA receptor imaging can be accomplished by radiolabeling derivates that activates benzodiazepine binding sites. There has been much research on flumazenil (FMZ) labeled with {sup 11}C-FMZ, a benzodiazepine derivate that is a selective, reversible antagonist to GABAA receptors. Recently, {sup 18}F-fluoroflumazenil (FFMZ) has been developed to overcome {sup 11}C's short half-life. {sup 18}F-FFMZ shows high selective affinity and good pharmacodynamics, and is a promising PET agent with better central benzodiazepine receptor imaging capabilities. In an epileptic focus, because the GABA/benzodiazepine receptor amount is decreased, using '1{sup 1}C-FMZ PET instead of {sup 18}F-FDG, PET, restrict the foci better and may also help find lesions better than high resolution MR. GABA{sub A} receptors are widely distributed in the cerebral cortex, and can be used as an viable neuronal marker. Therefore it can be used as a neuronal cell viability marker in cerebral ischemia. Also, GABA-receptors decrease in areas where neuronal plasticity develops, therefore, GABA imaging can be used to evaluate plasticity. Besides these usages, GABA receptors are related with psychological diseases, especially depression and schizophrenia as well as cerebral palsy, a motor-related disorder, so further in-depth studies are needed for these areas.

  18. GABA receptor imaging

    International Nuclear Information System (INIS)

    Lee, Jong Doo

    2007-01-01

    GABA is primary an inhibitory neurotransmitter that is localized in inhibitory interneurons. GABA is released from presynaptic terminals and functions by binding to GABA receptors. There are two types of GABA receptors, GABA A -receptor that allows chloride to pass through a ligand gated ion channel and GABA B -receptor that uses G-proteins for signaling. The GABA A -receptor has a GABA binding site as well as a benzodiazepine binding sites, which modulate GABA A -receptor function. Benzodiazepine GABAA receptor imaging can be accomplished by radiolabeling derivates that activates benzodiazepine binding sites. There has been much research on flumazenil (FMZ) labeled with 11 C-FMZ, a benzodiazepine derivate that is a selective, reversible antagonist to GABAA receptors. Recently, 18 F-fluoroflumazenil (FFMZ) has been developed to overcome 11 C's short half-life. 18 F-FFMZ shows high selective affinity and good pharmacodynamics, and is a promising PET agent with better central benzodiazepine receptor imaging capabilities. In an epileptic focus, because the GABA/benzodiazepine receptor amount is decreased, using '1 1 C-FMZ PET instead of 18 F-FDG, PET, restrict the foci better and may also help find lesions better than high resolution MR. GABA A receptors are widely distributed in the cerebral cortex, and can be used as an viable neuronal marker. Therefore it can be used as a neuronal cell viability marker in cerebral ischemia. Also, GABA-receptors decrease in areas where neuronal plasticity develops, therefore, GABA imaging can be used to evaluate plasticity. Besides these usages, GABA receptors are related with psychological diseases, especially depression and schizophrenia as well as cerebral palsy, a motor-related disorder, so further in-depth studies are needed for these areas

  19. Cognitive biases can affect moral intuitions about cognitive enhancement

    Directory of Open Access Journals (Sweden)

    Lucius eCaviola

    2014-10-01

    Full Text Available Research into cognitive biases that impair human judgment has mostly been applied to the area of economic decision-making. Ethical decision-making has been comparatively neglected. Since ethical decisions often involve very high individual as well as collective stakes, analyzing how cognitive biases affect them can be expected to yield important results. In this theoretical article, we consider the ethical debate about cognitive enhancement (CE and suggest a number of cognitive biases that are likely to affect moral intuitions and judgments about CE: status quo bias, loss aversion, risk aversion, omission bias, scope insensitivity, nature bias, and optimistic bias. We find that there are more well-documented biases that are likely to cause irrational aversion to CE than biases in the opposite direction. This suggests that common attitudes about CE are predominantly negatively biased. Within this new perspective, we hope that subsequent research will be able to elaborate this hypothesis and develop effective de-biasing techniques that can help increase the rationality of the public CE debate and thus improve our ethical decision-making.

  20. Bias correction of daily satellite precipitation data using genetic algorithm

    Science.gov (United States)

    Pratama, A. W.; Buono, A.; Hidayat, R.; Harsa, H.

    2018-05-01

    Climate Hazards Group InfraRed Precipitation with Stations (CHIRPS) was producted by blending Satellite-only Climate Hazards Group InfraRed Precipitation (CHIRP) with Stasion observations data. The blending process was aimed to reduce bias of CHIRP. However, Biases of CHIRPS on statistical moment and quantil values were high during wet season over Java Island. This paper presented a bias correction scheme to adjust statistical moment of CHIRP using observation precipitation data. The scheme combined Genetic Algorithm and Nonlinear Power Transformation, the results was evaluated based on different season and different elevation level. The experiment results revealed that the scheme robustly reduced bias on variance around 100% reduction and leaded to reduction of first, and second quantile biases. However, bias on third quantile only reduced during dry months. Based on different level of elevation, the performance of bias correction process is only significantly different on skewness indicators.

  1. Ombud’s Corner: defeating unconscious bias

    CERN Document Server

    Sudeshna Datta-Cockerill

    2016-01-01

    Do you have a tendency to switch off at meetings every time a particular colleague starts to speak? Is it obvious to you that your colleagues will never accept a peer as a project leader? And doesn’t that candidate from your own alma mater clearly have a definite edge over the others?   How do we come to these conclusions and what can we do to ensure that our decisions are based on objective criteria alone? Can we always be sure that we are not influenced by pre-conceived notions or prejudices that may unconsciously bias our thinking? Unconscious bias is a part of everyday life – it refers to the insidious influences that our backgrounds, cultural environments or personal experiences exert on the way in which we judge or assess people or situations. In the workplace, it has a negative impact on our goals and interactions when it causes us to make decisions based on generalisations or mental associations that we are not even aware of, and that have little or no bearing on the o...

  2. Bias During the Evaluation of Animal Studies?

    Directory of Open Access Journals (Sweden)

    Andrew Knight

    2012-02-01

    Full Text Available My recent book entitled The Costs and Benefits of Animal Experiments seeks to answer a key question within animal ethics, namely: is animal experimentation ethically justifiable? Or, more precisely, is it justifiable within the utilitarian cost:benefit framework that fundamentally underpins most regulations governing animal experimentation? To answer this question I reviewed more than 500 scientific publications describing animal studies, animal welfare impacts, and alternative research, toxicity testing and educational methodologies. To minimise bias I focused primarily on large-scale systematic reviews that had examined the human clinical and toxicological utility of animal studies. Despite this, Dr. Susanne Prankel recently reviewed my book in this journal, essentially accusing me of bias. However, she failed to provide any substantive evidence to refute my conclusions, let alone evidence of similar weight to that on which they are based. Those conclusions are, in fact, firmly based on utilitarian ethical reasoning, informed by scientific evidence of considerable strength, and I believe they are robust.

  3. Social influence bias: a randomized experiment.

    Science.gov (United States)

    Muchnik, Lev; Aral, Sinan; Taylor, Sean J

    2013-08-09

    Our society is increasingly relying on the digitized, aggregated opinions of others to make decisions. We therefore designed and analyzed a large-scale randomized experiment on a social news aggregation Web site to investigate whether knowledge of such aggregates distorts decision-making. Prior ratings created significant bias in individual rating behavior, and positive and negative social influences created asymmetric herding effects. Whereas negative social influence inspired users to correct manipulated ratings, positive social influence increased the likelihood of positive ratings by 32% and created accumulating positive herding that increased final ratings by 25% on average. This positive herding was topic-dependent and affected by whether individuals were viewing the opinions of friends or enemies. A mixture of changing opinion and greater turnout under both manipulations together with a natural tendency to up-vote on the site combined to create the herding effects. Such findings will help interpret collective judgment accurately and avoid social influence bias in collective intelligence in the future.

  4. Electronic properties of a biased graphene bilayer

    International Nuclear Information System (INIS)

    Castro, Eduardo V; Lopes dos Santos, J M B; Novoselov, K S; Morozov, S V; Geim, A K; Peres, N M R; Nilsson, Johan; Castro Neto, A H; Guinea, F

    2010-01-01

    We study, within the tight-binding approximation, the electronic properties of a graphene bilayer in the presence of an external electric field applied perpendicular to the system-a biased bilayer. The effect of the perpendicular electric field is included through a parallel plate capacitor model, with screening correction at the Hartree level. The full tight-binding description is compared with its four-band and two-band continuum approximations, and the four-band model is shown to always be a suitable approximation for the conditions realized in experiments. The model is applied to real biased bilayer devices, made out of either SiC or exfoliated graphene, and good agreement with experimental results is found, indicating that the model is capturing the key ingredients, and that a finite gap is effectively being controlled externally. Analysis of experimental results regarding the electrical noise and cyclotron resonance further suggests that the model can be seen as a good starting point for understanding the electronic properties of graphene bilayer. Also, we study the effect of electron-hole asymmetry terms, such as the second-nearest-neighbour hopping energies t' (in-plane) and γ 4 (inter-layer), and the on-site energy Δ.

  5. Linguistic intergroup bias in political communication.

    Science.gov (United States)

    Anolli, Luigi; Zurloni, Valentino; Riva, Giuseppe

    2006-07-01

    The Linguistic Intergroup Bias (LIB) illustrates the disposition to communicate positive in-group and negative out-group behaviors more abstractly than negative in-group and positive out-group behaviors. The present research examined the function of language in reinforcing this bias in political communication. To illustrate the LIB, the Linguistic Category Model (LCM) was used, including a nouns category. Because social stereotypes are usually conveyed by nominal terms, the aim was to observe the relationship between stereotypes and language in political communication. Moreover, we were interested in analyzing the psychological processes that drive the LIB. Therefore, we verified whether the LIB is more related to language abstractness than to agent-patient causality. Several political debates and interviews, which took place before the latest Italian provincial elections, were analyzed. Results suggested that the language politicians use in communicating about political groups are conceptualized as stereotypes rather than as trait-based categories. Moreover, it seems that the LIB could not be explained only at a lexical level. Social implications of the present findings in interpersonal relations and causal attribution were discussed.

  6. Glucocorticoid receptor modulators.

    Science.gov (United States)

    Meijer, Onno C; Koorneef, Lisa L; Kroon, Jan

    2018-06-01

    The glucocorticoid hormone cortisol acts throughout the body to support circadian processes and adaptation to stress. The glucocorticoid receptor is the target of cortisol and of synthetic glucocorticoids, which are used widely in the clinic. Both agonism and antagonism of the glucocorticoid receptor may be beneficial in disease, but given the wide expression of the receptor and involvement in various processes, beneficial effects are often accompanied by unwanted side effects. Selective glucocorticoid receptor modulators are ligands that induce a receptor conformation that allows activation of only a subset of downstream signaling pathways. Such molecules thereby combine agonistic and antagonistic properties. Here we discuss the mechanisms underlying selective receptor modulation and their promise in treating diseases in several organ systems where cortisol signaling plays a role. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  7. Mood-congruent free recall bias in anxious individuals is not a consequence of response bias.

    Science.gov (United States)

    Russo, Riccardo; Whittuck, Dora; Roberson, Debi; Dutton, Kevin; Georgiou, George; Fox, Elaine

    2006-05-01

    The status of mood-congruent free recall bias in anxious individuals was evaluated following incidental encoding of target words. Individuals with high and low levels of trait anxiety completed a modified Stroop task, which revealed an attentional bias for threat-related stimuli in anxious individuals. This group was significantly slower in naming the colour in which threat-related words were displayed compared to neutral words. In a subsequent free recall test for the words used in the modified Stroop task, anxious individuals recalled more threat-related words compared to low-anxious people. This difference was significant even when controlling for the false recall of items that had not been presented during study. These results support the view put forward by Russo, Fox, Bellinger, and Nguyen-Van-Tam (2001) that mood-congruent free recall bias in anxious individuals can be observed if the target material is encoded at a relatively shallow level. Moreover, contrary to Dowens and Calvo (2003), the current results show that the memory advantage for threat-related information in anxious individuals is not a consequence of response bias.

  8. Dengue virus receptor

    OpenAIRE

    Hidari, Kazuya I.P.J.; Suzuki, Takashi

    2011-01-01

    Dengue virus is an arthropod-borne virus transmitted by Aedes mosquitoes. Dengue virus causes fever and hemorrhagic disorders in humans and non-human primates. Direct interaction of the virus introduced by a mosquito bite with host receptor molecule(s) is crucial for virus propagation and the pathological progression of dengue diseases. Therefore, elucidation of the molecular mechanisms underlying the interaction between dengue virus and its receptor(s) in both humans and mosquitoes is essent...

  9. The evolution of social learning rules: payoff-biased and frequency-dependent biased transmission.

    Science.gov (United States)

    Kendal, Jeremy; Giraldeau, Luc-Alain; Laland, Kevin

    2009-09-21

    Humans and other animals do not use social learning indiscriminately, rather, natural selection has favoured the evolution of social learning rules that make selective use of social learning to acquire relevant information in a changing environment. We present a gene-culture coevolutionary analysis of a small selection of such rules (unbiased social learning, payoff-biased social learning and frequency-dependent biased social learning, including conformism and anti-conformism) in a population of asocial learners where the environment is subject to a constant probability of change to a novel state. We define conditions under which each rule evolves to a genetically polymorphic equilibrium. We find that payoff-biased social learning may evolve under high levels of environmental variation if the fitness benefit associated with the acquired behaviour is either high or low but not of intermediate value. In contrast, both conformist and anti-conformist biases can become fixed when environment variation is low, whereupon the mean fitness in the population is higher than for a population of asocial learners. Our examination of the population dynamics reveals stable limit cycles under conformist and anti-conformist biases and some highly complex dynamics including chaos. Anti-conformists can out-compete conformists when conditions favour a low equilibrium frequency of the learned behaviour. We conclude that evolution, punctuated by the repeated successful invasion of different social learning rules, should continuously favour a reduction in the equilibrium frequency of asocial learning, and propose that, among competing social learning rules, the dominant rule will be the one that can persist with the lowest frequency of asocial learning.

  10. Cognitive bias in forensic anthropology: visual assessment of skeletal remains is susceptible to confirmation bias.

    Science.gov (United States)

    Nakhaeizadeh, Sherry; Dror, Itiel E; Morgan, Ruth M

    2014-05-01

    An experimental study was designed to examine cognitive biases within forensic anthropological non-metric methods in assessing sex, ancestry and age at death. To investigate examiner interpretation, forty-one non-novice participants were semi randomly divided into three groups. Prior to conducting the assessment of the skeletal remains, two of the groups were given different extraneous contextual information regarding the sex, ancestry and age at death of the individual. The third group acted as a control group with no extraneous contextual information. The experiment was designed to investigate if the interpretation and conclusions of the skeletal remains would differ amongst participants within the three groups, and to assess whether the examiners would confirm or disagree with the given extraneous context when establishing a biological profile. The results revealed a significant biasing effect within the three groups, demonstrating a strong confirmation bias in the assessment of sex, ancestry and age at death. In assessment of sex, 31% of the participants in the control group concluded that the skeleton remains were male. In contrast, in the group that received contextual information that the remains were male, 72% concluded that the remains were male, and in the participant group where the context was that the remains were of a female, 0% of the participants concluded that the remains were male. Comparable results showing bias were found in assessing ancestry and age at death. These data demonstrate that cognitive bias can impact forensic anthropological non-metric methods on skeletal remains and affects the interpretation and conclusions of the forensic scientists. This empirical study is a step in establishing an evidence base approach for dealing with cognitive issues in forensic anthropological assessments, so as to enhance this valuable forensic science discipline. Copyright © 2013 Forensic Science Society. Published by Elsevier Ireland Ltd. All rights

  11. Linking genetic variants of the mineralocorticoid receptor and negative memory bias: Interaction with prior life adversity

    NARCIS (Netherlands)

    Vogel, S.; Gerritsen, L.; Oostrom, I.I.H. van; Arias Vasquez, A.; Rijpkema, M.J.P.; Joels, M.; Franke, B.; Tendolkar, I.; Fernandez, G.S.E.

    2014-01-01

    Substantial research has been conducted investigating the association between life adversity and genetic vulnerability for depression, but clear mechanistic links are rarely identified and investigation often focused on single genetic variants. Complex phenotypes like depression, however, are likely

  12. Novel strategies in drug discovery of the calcium-sensing receptor based on biased signaling

    DEFF Research Database (Denmark)

    Thomsen, Alex Rojas Bie; Smajilovic, Sanela; Bräuner-Osborne, Hans

    2012-01-01

    SR activating drug that selectively activates signaling pathways that inhibit PTH secretion while having no effect on signaling pathways involved in calcitonin secretion. Such a drug would have the same therapeutic value as cinacalcet in lowering PTH secretion while eliminating the side effect of hypocalcemia...

  13. Adenosine A2A Receptor Modulates the Activity of Globus Pallidus Neurons in Rats

    Directory of Open Access Journals (Sweden)

    Hui-Ling Diao

    2017-11-01

    Full Text Available The globus pallidus is a central nucleus in the basal ganglia motor control circuit. Morphological studies have revealed the expression of adenosine A2A receptors in the globus pallidus. To determine the modulation of adenosine A2A receptors on the activity of pallidal neurons in both normal and parkinsonian rats, in vivo electrophysiological and behavioral tests were performed in the present study. The extracellular single unit recordings showed that micro-pressure administration of adenosine A2A receptor agonist, CGS21680, regulated the pallidal firing activity. GABAergic neurotransmission was involved in CGS21680-induced modulation of pallidal neurons via a PKA pathway. Furthermore, application of two adenosine A2A receptor antagonists, KW6002 or SCH442416, mainly increased the spontaneous firing of pallidal neurons, suggesting that endogenous adenosine system modulates the activity of pallidal neurons through adenosine A2A receptors. Finally, elevated body swing test (EBST showed that intrapallidal microinjection of adenosine A2A receptor agonist/antagonist induced ipsilateral/contralateral-biased swing, respectively. In addition, the electrophysiological and behavioral findings also revealed that activation of dopamine D2 receptors by quinpirole strengthened KW6002/SCH442416-induced excitation of pallidal activity. Co-application of quinpirole with KW6002 or SCH442416 alleviated biased swing in hemi-parkinsonian rats. Based on the present findings, we concluded that pallidal adenosine A2A receptors may be potentially useful in the treatment of Parkinson's disease.

  14. Attentional Bias towards Positive Emotion Predicts Stress Resilience.

    Science.gov (United States)

    Thoern, Hanna A; Grueschow, Marcus; Ehlert, Ulrike; Ruff, Christian C; Kleim, Birgit

    2016-01-01

    There is extensive evidence for an association between an attentional bias towards emotionally negative stimuli and vulnerability to stress-related psychopathology. Less is known about whether selective attention towards emotionally positive stimuli relates to mental health and stress resilience. The current study used a modified Dot Probe task to investigate if individual differences in attentional biases towards either happy or angry emotional stimuli, or an interaction between these biases, are related to self-reported trait stress resilience. In a nonclinical sample (N = 43), we indexed attentional biases as individual differences in reaction time for stimuli preceded by either happy or angry (compared to neutral) face stimuli. Participants with greater attentional bias towards happy faces (but not angry faces) reported higher trait resilience. However, an attentional bias towards angry stimuli moderated this effect: The attentional bias towards happy faces was only predictive for resilience in those individuals who also endorsed an attentional bias towards angry stimuli. An attentional bias towards positive emotional stimuli may thus be a protective factor contributing to stress resilience, specifically in those individuals who also endorse an attentional bias towards negative emotional stimuli. Our findings therefore suggest a novel target for prevention and treatment interventions addressing stress-related psychopathology.

  15. Implementation of linear bias corrections for calorimeters at Mound

    International Nuclear Information System (INIS)

    Barnett, T.M.

    1993-01-01

    In the past, Mound has generally made relative bias corrections as part of the calibration of individual calorimeters. The correction made was the same over the entire operating range of the calorimeter, regardless of the magnitude of the range. Recently, an investigation was performed to check the relevancy of using linear bias corrections to calibrate the calorimeters. The bias is obtained by measuring calibrated plutonium and/or electrical heat standards over the operating range of the calorimeter. The bias correction is then calculated using a simple least squares fit (y = mx + b) of the bias in milliwatts over the operating range of the calorimeter in watts. The equation used is B i = B 0 + (B w * W m ), where B i is the bias at any given power in milliwatts, B 0 is the intercept (absolute bias in milliwatts), B w is the slope (relative bias in milliwatts per watt), and W m is the measured power in watts. The results of the study showed a decrease in the random error of bias corrected data for most of the calorimeters which are operated over a large wattage range (greater than an order of magnitude). The linear technique for bias correction has been fully implemented at Mound and has been included in the Technical Manual, ''A Measurement Control Program for Radiometric Calorimeters at Mound'' (MD-21900)

  16. Improved Correction of Misclassification Bias With Bootstrap Imputation.

    Science.gov (United States)

    van Walraven, Carl

    2018-07-01

    Diagnostic codes used in administrative database research can create bias due to misclassification. Quantitative bias analysis (QBA) can correct for this bias, requires only code sensitivity and specificity, but may return invalid results. Bootstrap imputation (BI) can also address misclassification bias but traditionally requires multivariate models to accurately estimate disease probability. This study compared misclassification bias correction using QBA and BI. Serum creatinine measures were used to determine severe renal failure status in 100,000 hospitalized patients. Prevalence of severe renal failure in 86 patient strata and its association with 43 covariates was determined and compared with results in which renal failure status was determined using diagnostic codes (sensitivity 71.3%, specificity 96.2%). Differences in results (misclassification bias) were then corrected with QBA or BI (using progressively more complex methods to estimate disease probability). In total, 7.4% of patients had severe renal failure. Imputing disease status with diagnostic codes exaggerated prevalence estimates [median relative change (range), 16.6% (0.8%-74.5%)] and its association with covariates [median (range) exponentiated absolute parameter estimate difference, 1.16 (1.01-2.04)]. QBA produced invalid results 9.3% of the time and increased bias in estimates of both disease prevalence and covariate associations. BI decreased misclassification bias with increasingly accurate disease probability estimates. QBA can produce invalid results and increase misclassification bias. BI avoids invalid results and can importantly decrease misclassification bias when accurate disease probability estimates are used.

  17. Understanding and Overcoming Implicit Gender Bias in Plastic Surgery.

    Science.gov (United States)

    Phillips, Nicole A; Tannan, Shruti C; Kalliainen, Loree K

    2016-11-01

    Although explicit sex-based discrimination has largely been deemed unacceptable in professional settings, implicit gender bias persists and results in a significant lack of parity in plastic surgery and beyond. Implicit gender bias is the result of a complex interplay of cultural and societal expectations, learned behaviors, and standardized associations. As such, both male and female surgeons are subject to its influence. A review of the literature was conducted, examining theories of gender bias, current manifestations of gender bias in plastic surgery and other fields, and interventions designed to address gender bias. Multiple studies demonstrate persistent gender bias that impacts female physicians at all levels of training. Several institutions have enacted successful interventions to identify and address gender bias. Explicit gender bias has largely disappeared, yet unconscious or implicit gender bias persists. A wide-scale commitment to addressing implicit gender bias in plastic surgery is necessary and overdue. Recommendations include immediate actions that can be undertaken on an individual basis, and changes that should be implemented at a national and international level by leaders in the field.

  18. Altering attentional control settings causes persistent biases of visual attention.

    Science.gov (United States)

    Knight, Helen C; Smith, Daniel T; Knight, David C; Ellison, Amanda

    2016-01-01

    Attentional control settings have an important role in guiding visual behaviour. Previous work within cognitive psychology has found that the deployment of general attentional control settings can be modulated by training. However, research has not yet established whether long-term modifications of one particular type of attentional control setting can be induced. To address this, we investigated persistent alterations to feature search mode, also known as an attentional bias, towards an arbitrary stimulus in healthy participants. Subjects were biased towards the colour green by an information sheet. Attentional bias was assessed using a change detection task. After an interval of either 1 or 2 weeks, participants were then retested on the same change detection task, tested on a different change detection task where colour was irrelevant, or were biased towards an alternative colour. One experiment included trials in which the distractor stimuli (but never the target stimuli) were green. The key finding was that green stimuli in the second task attracted attention, despite this impairing task performance. Furthermore, inducing a second attentional bias did not override the initial bias toward green objects. The attentional bias also persisted for at least two weeks. It is argued that this persistent attentional bias is mediated by a chronic change to participants' attentional control settings, which is aided by long-term representations involving contextual cueing. We speculate that similar changes to attentional control settings and continuous cueing may relate to attentional biases observed in psychopathologies. Targeting these biases may be a productive approach to treatment.

  19. Assessing the extent of non-stationary biases in GCMs

    Science.gov (United States)

    Nahar, Jannatun; Johnson, Fiona; Sharma, Ashish

    2017-06-01

    General circulation models (GCMs) are the main tools for estimating changes in the climate for the future. The imperfect representation of climate models introduces biases in the simulations that need to be corrected prior to their use for impact assessments. Bias correction methods generally assume that the bias calculated over the historical period does not change and can be applied to the future. This study investigates this assumption by considering the extent and nature of bias non-stationarity using 20th century precipitation and temperature simulations from six CMIP5 GCMs across Australia. Four statistics (mean, standard deviation, 10th and 90th quantiles) in monthly and seasonal biases are obtained for three different time window lengths (10, 25 and 33 years) to examine the properties of bias over time. This approach is repeated for two different phases of the Interdecadal Pacific Oscillation (IPO), which is known to have strong influences on the Australian climate. It is found that bias non-stationarity at decadal timescales is indeed an issue over some of Australia for some GCMs. When considering interdecadal variability there are significant difference in the bias between positive and negative phases of the IPO. Regional analyses confirmed these findings with the largest differences seen on the east coast of Australia, where IPO impacts tend to be the strongest. The nature of the bias non-stationarity found in this study suggests that it will be difficult to modify existing bias correction approaches to account for non-stationary biases. A more practical approach for impact assessments that use bias correction maybe to use a selection of GCMs where the assumption of bias non-stationarity holds.

  20. Measurement of Minimum Bias Observables with ATLAS

    CERN Document Server

    Kvita, Jiri; The ATLAS collaboration

    2017-01-01

    The modelling of Minimum Bias (MB) is a crucial ingredient to learn about the description of soft QCD processes. It has also a significant relevance for the simulation of the environment at the LHC with many concurrent pp interactions (“pileup”). The ATLAS collaboration has provided new measurements of the inclusive charged particle multiplicity and its dependence on transverse momentum and pseudorapidity in special data sets with low LHC beam currents, recorded at center of mass energies of 8 TeV and 13 TeV. The measurements cover a wide spectrum using charged particle selections with minimum transverse momentum of both 100 MeV and 500 MeV and in various phase space regions of low and high charged particle multiplicities.

  1. Judgment under Uncertainty: Heuristics and Biases.

    Science.gov (United States)

    Tversky, A; Kahneman, D

    1974-09-27

    This article described three heuristics that are employed in making judgements under uncertainty: (i) representativeness, which is usually employed when people are asked to judge the probability that an object or event A belongs to class or process B; (ii) availability of instances or scenarios, which is often employed when people are asked to assess the frequency of a class or the plausibility of a particular development; and (iii) adjustment from an anchor, which is usually employed in numerical prediction when a relevant value is available. These heuristics are highly economical and usually effective, but they lead to systematic and predictable errors. A better understanding of these heuristics and of the biases to which they lead could improve judgements and decisions in situations of uncertainty.

  2. Angular biasing in implicit Monte-Carlo

    International Nuclear Information System (INIS)

    Zimmerman, G.B.

    1994-01-01

    Calculations of indirect drive Inertial Confinement Fusion target experiments require an integrated approach in which laser irradiation and radiation transport in the hohlraum are solved simultaneously with the symmetry, implosion and burn of the fuel capsule. The Implicit Monte Carlo method has proved to be a valuable tool for the two dimensional radiation transport within the hohlraum, but the impact of statistical noise on the symmetric implosion of the small fuel capsule is difficult to overcome. We present an angular biasing technique in which an increased number of low weight photons are directed at the imploding capsule. For typical parameters this reduces the required computer time for an integrated calculation by a factor of 10. An additional factor of 5 can also be achieved by directing even smaller weight photons at the polar regions of the capsule where small mass zones are most sensitive to statistical noise

  3. Reference List About Implicit and Unconscious Bias

    DEFF Research Database (Denmark)

    Munar, Ana Maria; Villeseche, Florence; Wiedemann, Cecilie Dam

    to publications accessible through the CBS library website and/or specifications of where and how to access each publication. In addition, as part of this effort and in line with the task list of the Council for Diversity and Inclusion, the report “Gender and Leadership Practices at Copenhagen Business School......The compilation of this reference list is one of the initiatives of the action plan developed by the Council for Diversity and Inclusion at Copenhagen Business School (CBS). This reference list is the first in a series of efforts initiated by this Council to develop an academic resource pool......, everyday human thought and activity” (Hardin and Banaji, 2013, pp. 13-14). Research also indicates that it is possible to implement procedures and strategic actions that help reduce implicit biases (Devine, Forscher, Austin, & Cox, 2012). Although extensive, this list does not include all existing academic...

  4. Survivor bias in Mendelian randomization analysis

    DEFF Research Database (Denmark)

    Vansteelandt, Stijn; Dukes, Oliver; Martinussen, Torben

    2017-01-01

    Mendelian randomization studies employ genotypes as experimental handles to infer the effect of genetically modified exposures (e.g. vitamin D exposure) on disease outcomes (e.g. mortality). The statistical analysis of these studies makes use of the standard instrumental variables framework. Many...... of these studies focus on elderly populations, thereby ignoring the problem of left truncation, which arises due to the selection of study participants being conditional upon surviving up to the time of study onset. Such selection, in general, invalidates the assumptions on which the instrumental variables...... analysis rests. We show that Mendelian randomization studies of adult or elderly populations will therefore, in general, return biased estimates of the exposure effect when the considered genotype affects mortality; in contrast, standard tests of the causal null hypothesis that the exposure does not affect...

  5. Essentialism Promotes Children's Inter-ethnic Bias

    Directory of Open Access Journals (Sweden)

    Gil eDiesendruck

    2015-08-01

    Full Text Available The present study investigated the developmental foundation of the relation between social essentialism and attitudes. Forty-eight Jewish Israeli secular 6-year-olds were exposed to either a story emphasizing essentialism about ethnicity, or stories controlling for the salience of ethnicity or essentialism per se. After listening to a story, children’s attitudes were assessed in a drawing and in an IAT task. Compared to the control conditions, children in the ethnic essentialism condition drew a Jewish and an Arab character as farther apart from each other, and the Jewish character with a more positive affect than the Arab character. Moreover, boys in the ethnic essentialism condition manifested a stronger bias in the IAT. These findings reveal an early link between essentialism and inter-group attitudes.

  6. Internal bias field in glycine phosphite crystal

    International Nuclear Information System (INIS)

    Nayeem, Jannatul; Wakabayashi, Hiroshi; Kikuta, Toshio; Yamazaki, Toshinari; Nakatani, Noriyuki

    2003-01-01

    The distributions of internal bias field E b have been investigated under the carbon-powder pattern and mercury electrode techniques in GPI ferroelectric crystals. Polarity and intensity of E b are distributed depending on crystal growth sectors. Crystal symmetry 2/m is observed obviously in the distribution of E b . The polarities of E b are head-to-head manner in those growth sectors where a surface is growing parallel to the crystallographic a-axis and tail-to-tail manner in the other growth sectors in the crystal. The maximum intensity of E b is found in the sectors (010) where the growing surfaces are perpendicular to the ferroelectric b-axis

  7. Information filtering via biased heat conduction

    Science.gov (United States)

    Liu, Jian-Guo; Zhou, Tao; Guo, Qiang

    2011-09-01

    The process of heat conduction has recently found application in personalized recommendation [Zhou , Proc. Natl. Acad. Sci. USA PNASA60027-842410.1073/pnas.1000488107107, 4511 (2010)], which is of high diversity but low accuracy. By decreasing the temperatures of small-degree objects, we present an improved algorithm, called biased heat conduction, which could simultaneously enhance the accuracy and diversity. Extensive experimental analyses demonstrate that the accuracy on MovieLens, Netflix, and Delicious datasets could be improved by 43.5%, 55.4% and 19.2%, respectively, compared with the standard heat conduction algorithm and also the diversity is increased or approximately unchanged. Further statistical analyses suggest that the present algorithm could simultaneously identify users' mainstream and special tastes, resulting in better performance than the standard heat conduction algorithm. This work provides a creditable way for highly efficient information filtering.

  8. Theory of quantum diffusion in biased semiconductors

    CERN Document Server

    Bryksin, V V

    2003-01-01

    A general theory is developed to describe diffusion phenomena in biased semiconductors and semiconductor superlattices. It is shown that the Einstein relation is not applicable for all field strengths so that the calculation of the field-mediated diffusion coefficient represents a separate task. Two quite different diffusion contributions are identified. The first one disappears when the dipole operator commutes with the Hamiltonian. It plays an essential role in the theory of small polarons. The second contribution is obtained from a quantity that is the solution of a kinetic equation but that cannot be identified with the carrier distribution function. This is in contrast to the drift velocity, which is closely related to the distribution function. A general expression is derived for the quantum diffusion regime, which allows a clear physical interpretation within the hopping picture.

  9. The psychological price of media bias.

    Science.gov (United States)

    Babad, Elisha

    2005-12-01

    Media bias was investigated through the effects of a TV interviewer's preferential behavior on the image of the interviewee in the eyes of the viewers. Judges viewed a political interview with either a friendly or a hostile interviewer then rated their impressions of the interviewed politician, whose behavior was identical in all conditions. The preferential nonverbal behavior of the interviewer (controlling for recognition and comprehension of verbal content) systematically influenced viewers' ratings of the politician. The effect consisted mainly of damage to the politician in the hostile interviewer condition. Describing the interviewee as a professor yielded a similar preferential behavior effect. A strong halo effect was identified, but it was ruled out as the mechanism accounting for the interviewer effect.

  10. PLUTINO DETECTION BIASES, INCLUDING THE KOZAI RESONANCE

    International Nuclear Information System (INIS)

    Lawler, S. M.; Gladman, B.

    2013-01-01

    Because of their relative proximity within the trans-Neptunian region, the plutinos (objects in the 3:2 mean-motion resonance with Neptune) are numerous in flux-limited catalogs, and well-studied theoretically. We perform detailed modeling of the on-sky detection biases for plutinos, with special attention to those that are simultaneously in the Kozai resonance. In addition to the normal 3:2 resonant argument libration, Kozai plutinos also show periodic oscillations in eccentricity and inclination, coupled to the argument of perihelion (ω) oscillation. Due to the mean-motion resonance, plutinos avoid coming to pericenter near Neptune's current position in the ecliptic plane. Because Kozai plutinos are restricted to certain values of ω, perihelion always occurs out of the ecliptic plane, biasing ecliptic surveys against finding these objects. The observed Kozai plutino fraction f koz obs has been measured by several surveys, finding values between 8% and 25%, while the true Kozai plutino fraction f koz true has been predicted to be between 10% and 30% by different giant planet migration simulations. We show that f koz obs varies widely depending on the ecliptic latitude and longitude of the survey, so debiasing to find the true ratio is complex. Even a survey that covers most or all of the sky will detect an apparent Kozai fraction that is different from f koz true . We present a map of the on-sky plutino Kozai fraction that would be detected by all-sky flux-limited surveys. This will be especially important for the Panoramic Survey Telescope and Rapid Response System and Large Synoptic Survey Telescope projects, which may detect large numbers of plutinos as they sweep the sky. f koz true and the distribution of the orbital elements of Kozai plutinos may be a diagnostic of giant planet migration; future migration simulations should provide details on their resonant Kozai populations.

  11. Selection bias and the perils of benchmarking.

    Science.gov (United States)

    Denrell, Jerker

    2005-04-01

    To find the secrets of business success, what could be more natural than studying successful businesses? In fact, nothing could be more dangerous, warns this Stanford professor. Generalizing from the examples of successful companies is like generalizing about New England weather from data taken only in the summer. That's essentially what businesspeople do when they learn from good examples and what consultants, authors, and researchers do when they study only existing companies or--worse yet--only high-performing companies. They reach conclusions from unrepresentative data samples, falling into the classic statistical trap of selection bias. Drawing on a wealth of case studies, for instance, one researcher concluded that great leaders share two key traits: They persist, often despite initial failures, and they are able to persuade others to join them. But those traits are also the hallmarks of spectacularly unsuccessful entrepreneurs, who must persist in the face of failure to incur large losses and must be able to persuade others to pour their money down the drain. To discover what makes a business successful, then, managers should look at both successes and failures. Otherwise, they will overvalue risky business practices, seeing only those companies that won big and not the ones that lost dismally. They will not be able to tell if their current good fortune stems from smart business practices or if they are actually coasting on past accomplishments or good luck. Fortunately, economists have developed relatively simple tools that can correct for selection bias even when data about failed companies are hard to come by. Success may be inspirational, but managers are more likely to find the secrets of high performance if they give the stories of their competitors'failures as full a hearing as they do the stories of dazzling successes.

  12. SURVIVAL ANALYSIS AND LENGTH-BIASED SAMPLING

    Directory of Open Access Journals (Sweden)

    Masoud Asgharian

    2010-12-01

    Full Text Available When survival data are colleted as part of a prevalent cohort study, the recruited cases have already experienced their initiating event. These prevalent cases are then followed for a fixed period of time at the end of which the subjects will either have failed or have been censored. When interests lies in estimating the survival distribution, from onset, of subjects with the disease, one must take into account that the survival times of the cases in a prevalent cohort study are left truncated. When it is possible to assume that there has not been any epidemic of the disease over the past period of time that covers the onset times of the subjects, one may assume that the underlying incidence process that generates the initiating event times is a stationary Poisson process. Under such assumption, the survival times of the recruited subjects are called “lengthbiased”. I discuss the challenges one is faced with in analyzing these type of data. To address the theoretical aspects of the work, I present asymptotic results for the NPMLE of the length-biased as well as the unbiased survival distribution. I also discuss estimating the unbiased survival function using only the follow-up time. This addresses the case that the onset times are either unknown or known with uncertainty. Some of our most recent work and open questions will be presented. These include some aspects of analysis of covariates, strong approximation, functional LIL and density estimation under length-biased sampling with right censoring. The results will be illustrated with survival data from patients with dementia, collected as part of the Canadian Study of Health and Aging (CSHA.

  13. Bias-correction in vector autoregressive models: A simulation study

    DEFF Research Database (Denmark)

    Engsted, Tom; Pedersen, Thomas Quistgaard

    We analyze and compare the properties of various methods for bias-correcting parameter estimates in vector autoregressions. First, we show that two analytical bias formulas from the existing literature are in fact identical. Next, based on a detailed simulation study, we show that this simple...... and easy-to-use analytical bias formula compares very favorably to the more standard but also more computer intensive bootstrap bias-correction method, both in terms of bias and mean squared error. Both methods yield a notable improvement over both OLS and a recently proposed WLS estimator. We also...... of pushing an otherwise stationary model into the non-stationary region of the parameter space during the process of correcting for bias....

  14. Importance biasing quality criterion based on contribution response theory

    International Nuclear Information System (INIS)

    Borisov, N.M.; Panin, M.P.

    2001-01-01

    The report proposes a visual criterion of importance biasing both of forward and adjoint simulation. The similarity of contribution Monte Carlo and importance biasing random collision event distribution is proved. The conservation of total number of random trajectory crossings of surfaces, which separate the source and the detector is proposed as importance biasing quality criterion. The use of this criterion is demonstrated on the example of forward vs. adjoint importance biasing in gamma ray deep penetration problem. The larger amount of published data on forward field characteristics than on adjoint leads to the more accurate approximation of adjoint importance function in comparison to forward, for it adjoint importance simulation is more effective than forward. The proposed criterion indicates it visually, showing the most uniform distribution of random trajectory crossing events for the most effective importance biasing parameters and pointing to the direction of tuning importance biasing parameters. (orig.)

  15. Mechanism for and method of biasing magnetic sensor

    Science.gov (United States)

    Kautz, David R.

    2007-12-04

    A magnetic sensor package having a biasing mechanism involving a coil-generated, resistor-controlled magnetic field for providing a desired biasing effect. In a preferred illustrated embodiment, the package broadly comprises a substrate; a magnetic sensor element; a biasing mechanism, including a coil and a first resistance element; an amplification mechanism; a filter capacitor element; and an encapsulant. The sensor is positioned within the coil. A current applied to the coil produces a biasing magnetic field. The biasing magnetic field is controlled by selecting a resistance value for the first resistance element which achieves the desired biasing effect. The first resistance element preferably includes a plurality of selectable resistors, the selection of one or more of which sets the resistance value.

  16. Angiotensin type 2 receptors

    DEFF Research Database (Denmark)

    Sumners, Colin; de Kloet, Annette D; Krause, Eric G

    2015-01-01

    In most situations, the angiotensin AT2-receptor (AT2R) mediates physiological actions opposing those mediated by the AT1-receptor (AT1R), including a vasorelaxant effect. Nevertheless, experimental evidence vastly supports that systemic application of AT2R-agonists is blood pressure neutral...

  17. Optimum biasing of integral equations in Monte Carlo calculations

    International Nuclear Information System (INIS)

    Hoogenboom, J.E.

    1979-01-01

    In solving integral equations and estimating average values with the Monte Carlo method, biasing functions may be used to reduce the variancee of the estimates. A simple derivation was used to prove the existence of a zero-variance collision estimator if a specific biasing function and survival probability are applied. This optimum biasing function is the same as that used for the well known zero-variance last-event estimator

  18. Bias Correction with Jackknife, Bootstrap, and Taylor Series

    OpenAIRE

    Jiao, Jiantao; Han, Yanjun; Weissman, Tsachy

    2017-01-01

    We analyze the bias correction methods using jackknife, bootstrap, and Taylor series. We focus on the binomial model, and consider the problem of bias correction for estimating $f(p)$, where $f \\in C[0,1]$ is arbitrary. We characterize the supremum norm of the bias of general jackknife and bootstrap estimators for any continuous functions, and demonstrate the in delete-$d$ jackknife, different values of $d$ may lead to drastically different behavior in jackknife. We show that in the binomial ...

  19. Procedures for Dealing with Optimism Bias in Transport Planning

    DEFF Research Database (Denmark)

    Flyvbjerg, Bent; Glenting, Carsten; Rønnest, Arne Kvist

    of the document are to provide empirically based optimism bias up-lifts for selected reference classes of transport infrastructure projects and provide guidance on using the established uplifts to produce more realistic forecasts for the individual project's capital expenditures. Furthermore, the underlying...... causes and institutional context for optimism bias in British transport projects are discussed and some possibilities for reducing optimism bias in project preparation and decision-making are identified....

  20. A pupillary index of susceptibility to decision biases

    OpenAIRE

    Eldar, Eran; Felso, Valkyrie; Cohen, Jonathan; Niv, Yael

    2018-01-01

    Under what conditions do humans systematically deviate from rational decision making? Here we show that pupillary indices of low neural gain are associated with strong and consistent biases across six different extensively-studied decision making tasks, whereas indices of high gain are associated with weak or absent biases. Lower susceptibility to biases, however, comes at the cost of indecisiveness, or alternatively, prolonged deliberation time. We explain the association between low gain an...

  1. Media Bias and Advertising: Evidence from German Car Magazines

    OpenAIRE

    Dewenter, Ralf; Heimeshoff, Ulrich

    2011-01-01

    This paper investigates the existence of a possible media bias by analyzing the impact of automobile manufactures' advertisements on automobile reviews in German car magazines. By accounting for both endogeneity and sample selection we find a positive impact of advertising volumes on test scores. Moreover, also a home bias in terms of higher scores for German cars is observable. We account these results as some evidence for a media bias, induced by the two-sidedness of the markets.

  2. Glutamate receptor agonists

    DEFF Research Database (Denmark)

    Vogensen, Stine Byskov; Greenwood, Jeremy R; Bunch, Lennart

    2011-01-01

    The neurotransmitter (S)-glutamate [(S)-Glu] is responsible for most of the excitatory neurotransmission in the central nervous system. The effect of (S)-Glu is mediated by both ionotropic and metabotropic receptors. Glutamate receptor agonists are generally a-amino acids with one or more...... stereogenic centers due to strict requirements in the agonist binding pocket of the activated state of the receptor. By contrast, there are many examples of achiral competitive antagonists. The present review addresses how stereochemistry affects the activity of glutamate receptor ligands. The review focuses...... mainly on agonists and discusses stereochemical and conformational considerations as well as biostructural knowledge of the agonist binding pockets, which is useful in the design of glutamate receptor agonists. Examples are chosen to demonstrate how stereochemistry not only determines how the agonist...

  3. AMPA receptor ligands

    DEFF Research Database (Denmark)

    Strømgaard, Kristian; Mellor, Ian

    2004-01-01

    Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (AMPAR), subtype of the ionotropic glutamate receptors (IGRs), mediate fast synaptic transmission in the central nervous system (CNS), and are involved in many neurological disorders, as well as being a key player in the f......Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (AMPAR), subtype of the ionotropic glutamate receptors (IGRs), mediate fast synaptic transmission in the central nervous system (CNS), and are involved in many neurological disorders, as well as being a key player...... in the formation of memory. Hence, ligands affecting AMPARs are highly important for the study of the structure and function of this receptor, and in this regard polyamine-based ligands, particularly polyamine toxins, are unique as they selectively block Ca2+ -permeable AMPARs. Indeed, endogenous intracellular...

  4. The role of unconscious bias in surgical safety and outcomes.

    Science.gov (United States)

    Santry, Heena P; Wren, Sherry M

    2012-02-01

    Racial, ethnic, and gender disparities in health outcomes are a major challenge for the US health care system. Although the causes of these disparities are multifactorial, unconscious bias on the part of health care providers plays a role. Unconscious bias occurs when subconscious prejudicial beliefs about stereotypical individual attributes result in an automatic and unconscious reaction and/or behavior based on those beliefs. This article reviews the evidence in support of unconscious bias and resultant disparate health outcomes. Although unconscious bias cannot be entirely eliminated, acknowledging it, encouraging empathy, and understanding patients' sociocultural context promotes just, equitable, and compassionate care to all patients. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. A systematic review of context bias in invasion biology.

    Directory of Open Access Journals (Sweden)

    Robert J Warren

    Full Text Available The language that scientists use to frame biological invasions may reveal inherent bias-including how data are interpreted. A frequent critique of invasion biology is the use of value-laden language that may indicate context bias. Here we use a systematic study of language and interpretation in papers drawn from invasion biology to evaluate whether there is a link between the framing of papers and the interpretation of results. We also examine any trends in context bias in biological invasion research. We examined 651 peer-reviewed invasive species competition studies and implemented a rigorous systematic review to examine bias in the presentation and interpretation of native and invasive competition in invasion biology. We predicted that bias in the presentation of invasive species is increasing, as suggested by several authors, and that bias against invasive species would result in misinterpreting their competitive dominance in correlational observational studies compared to causative experimental studies. We indeed found evidence of bias in the presentation and interpretation of invasive species research; authors often introduced research with invasive species in a negative context and study results were interpreted against invasive species more in correlational studies. However, we also found a distinct decrease in those biases since the mid-2000s. Given that there have been several waves of criticism from scientists both inside and outside invasion biology, our evidence suggests that the subdiscipline has somewhat self-corrected apparent biases.

  6. The lighter side of advertising: investigating posing and lighting biases.

    Science.gov (United States)

    Thomas, Nicole A; Burkitt, Jennifer A; Patrick, Regan E; Elias, Lorin J

    2008-11-01

    People tend to display the left cheek when posing for a portrait; however, this effect does not appear to generalise to advertising. The amount of body visible in the image and the sex of the poser might also contribute to the posing bias. Portraits also exhibit lateral lighting biases, with most images being lit from the left. This effect might also be present in advertisements. A total of 2801 full-page advertisements were sampled and coded for posing direction, lighting direction, sex of model, and amount of body showing. Images of females showed an overall leftward posing bias, but the biases in males depended on the amount of body visible. Males demonstrated rightward posing biases for head-only images. Overall, images tended to be lit from the top left corner. The two factors of posing and lighting biases appear to influence one another. Leftward-lit images had more leftward poses than rightward, while the opposite occurred for rightward-lit images. Collectively, these results demonstrate that the posing biases in advertisements are dependent on the amount of body showing in the image, and that biases in lighting direction interact with these posing biases.

  7. Modeling Temporal Bias of Uplift Events in Recommender Systems

    KAUST Repository

    Altaf, Basmah

    2013-05-08

    Today, commercial industry spends huge amount of resources in advertisement campaigns, new marketing strategies, and promotional deals to introduce their product to public and attract a large number of customers. These massive investments by a company are worthwhile because marketing tactics greatly influence the consumer behavior. Alternatively, these advertising campaigns have a discernible impact on recommendation systems which tend to promote popular items by ranking them at the top, resulting in biased and unfair decision making and loss of customers’ trust. The biasing impact of popularity of items on recommendations, however, is not fixed, and varies with time. Therefore, it is important to build a bias-aware recommendation system that can rank or predict items based on their true merit at given time frame. This thesis proposes a framework that can model the temporal bias of individual items defined by their characteristic contents, and provides a simple process for bias correction. Bias correction is done either by cleaning the bias from historical training data that is used for building predictive model, or by ignoring the estimated bias from the predictions of a standard predictor. Evaluated on two real world datasets, NetFlix and MovieLens, our framework is shown to be able to estimate and remove the bias as a result of adopted marketing techniques from the predicted popularity of items at a given time.

  8. Understanding antigay bias from a cognitive-affective-behavioral perspective.

    Science.gov (United States)

    Callender, Kevin A

    2015-01-01

    In general, United States citizens have become increasingly more accepting of lesbians and gay men over the past few decades. Despite this shift in public attitudes, antigay bias remains openly tolerated, accepted, practiced, and even defended by a substantial portion of the population. This article reviews why and how antigay bias persists using a cognitive-affective-behavioral perspective that touches on sociocognitive factors such as prejudice and stereotyping, as well as features unique to antigay bias, such as its concealable nature. The article concludes with a discussion of how understanding modern antigay bias through a cognitive-affective-behavioral lens can be applied to reduce discrimination against gays and lesbians.

  9. Effects of Bias Modification Training in Binge Eating Disorder.

    Science.gov (United States)

    Schmitz, Florian; Svaldi, Jennifer

    2017-09-01

    Food-related attentional biases have been identified as maintaining factors in binge eating disorder (BED) as they can trigger a binge episode. Bias modification training may reduce symptoms, as it has been shown to be successful in other appetitive disorders. The aim of this study was to assess and modify food-related biases in BED. It was tested whether biases could be increased and decreased by means of a modified dot-probe paradigm, how long such bias modification persisted, and whether this affected subjective food craving. Participants were randomly assigned to a bias enhancement (attend to food stimulus) group or to a bias reduction (avoid food stimulus) group. Food-related attentional bias was found to be successfully reduced in the bias-reduction group, and effects persisted briefly. Additionally, subjective craving for food was influenced by the intervention, and possible mechanisms are discussed. Given these promising initial results, future research should investigate boundary conditions of the experimental intervention to understand how it could complement treatment of BED. Copyright © 2017. Published by Elsevier Ltd.

  10. Assessing atmospheric bias correction for dynamical consistency using potential vorticity

    International Nuclear Information System (INIS)

    Rocheta, Eytan; Sharma, Ashish; Evans, Jason P

    2014-01-01

    Correcting biases in atmospheric variables prior to impact studies or dynamical downscaling can lead to new biases as dynamical consistency between the ‘corrected’ fields is not maintained. Use of these bias corrected fields for subsequent impact studies and dynamical downscaling provides input conditions that do not appropriately represent intervariable relationships in atmospheric fields. Here we investigate the consequences of the lack of dynamical consistency in bias correction using a measure of model consistency—the potential vorticity (PV). This paper presents an assessment of the biases present in PV using two alternative correction techniques—an approach where bias correction is performed individually on each atmospheric variable, thereby ignoring the physical relationships that exists between the multiple variables that are corrected, and a second approach where bias correction is performed directly on the PV field, thereby keeping the system dynamically coherent throughout the correction process. In this paper we show that bias correcting variables independently results in increased errors above the tropopause in the mean and standard deviation of the PV field, which are improved when using the alternative proposed. Furthermore, patterns of spatial variability are improved over nearly all vertical levels when applying the alternative approach. Results point to a need for a dynamically consistent atmospheric bias correction technique which results in fields that can be used as dynamically consistent lateral boundaries in follow-up downscaling applications. (letter)

  11. Is Czech Export still Biased towards the Eastern Markets?

    Directory of Open Access Journals (Sweden)

    Lucie Coufalová

    2017-01-01

    Full Text Available There were special relationships among the COMECON members during the period of the centrally planning system. Czechoslovak trade/export was naturally biased towards these countries. The goal of this paper is to find out if there still exists any export bias towards the Russian or the ex‑COMECON markets. In our research approach we use gravity models. We revealed that taking into consideration growth in GDP, geographical distance and institutions there is no bias towards the Russian or the CIS markets. But we discovered a bias towards the ex‑COMECON contemporary members of the EU.

  12. Positioning of Weight Bias: Moving towards Social Justice.

    Science.gov (United States)

    Nutter, Sarah; Russell-Mayhew, Shelly; Alberga, Angela S; Arthur, Nancy; Kassan, Anusha; Lund, Darren E; Sesma-Vazquez, Monica; Williams, Emily

    2016-01-01

    Weight bias is a form of stigma with detrimental effects on the health and wellness of individuals with large bodies. Researchers from various disciplines have recognized weight bias as an important topic for public health and for professional practice. To date, researchers from various areas have approached weight bias from independent perspectives and from differing theoretical orientations. In this paper, we examined the similarities and differences between three perspectives (i.e., weight-centric, non-weight-centric (health-centric), and health at every size) used to understand weight bias and approach weight bias research with regard to (a) language about people with large bodies, (b) theoretical position, (c) identified consequences of weight bias, and (d) identified influences on weight-based social inequity. We suggest that, despite differences, each perspective acknowledges the negative influences that position weight as being within individual control and the negative consequences of weight bias. We call for recognition and discussion of weight bias as a social justice issue in order to change the discourse and professional practices extended towards individuals with large bodies. We advocate for an emphasis on social justice as a uniting framework for interdisciplinary research on weight bias.

  13. Health risk perception, optimistic bias, and personal satisfaction.

    Science.gov (United States)

    Bränström, Richard; Brandberg, Yvonne

    2010-01-01

    To examine change in risk perception and optimistic bias concerning behavior-linked health threats and environmental health threats between adolescence and young adulthood and how these factors related to personal satisfaction. In 1996 and 2002, 1624 adolescents responded to a mailed questionnaire. Adolescents showed strong positive optimistic bias concerning behaviorlinked risks, and this optimistic bias increased with age. Increase in optimistic bias over time predicted increase in personal satisfaction. The capacity to process and perceive potential threats in a positive manner might be a valuable human ability positively influencing personal satisfaction and well-being.

  14. Awareness and minimisation of systematic bias in research.

    LENUS (Irish Health Repository)

    Malone, Helen

    2014-03-01

    A major goal of nursing and midwifery is the delivery of evidence-based practice. Consequently, it is essential for the quality and safety of patient\\/client care that policy makers, educators and practitioners are aware of the presence of potential systematic bias in research practice and research publications so that only sound evidence translates into practice. The main aim of this paper is to highlight the need for ongoing awareness of the potential presence of systematic bias in research practice, to explore commonly reported types of systematic bias and to report some methods that can be applied to minimise systematic bias in research.

  15. Giant exchange bias in MnPd/Co bilayers

    International Nuclear Information System (INIS)

    Nguyen Thanh Nam; Nguyen Phu Thuy; Nguyen Anh Tuan; Nguyen Nguyen Phuoc; Suzuki, Takao

    2007-01-01

    A systematic study of exchange bias in MnPd/Co bilayers has been carried out, where the dependences of exchange bias, unidirectional anisotropy constant and coercivity on the thicknesses of MnPd and Co layers were investigated. A huge unidirectional anisotropy constant, J K =2.5erg/cm 2 was observed, which is in reasonable agreement with the theoretical prediction based on the model by Meiklejohn and Bean. The angular dependences of exchange bias field and coercivity have also been examined showing that both exchange bias and coercivity follow 1/cosα rule

  16. Investigating vulnerability to eating disorders: biases in emotional processing.

    Science.gov (United States)

    Pringle, A; Harmer, C J; Cooper, M J

    2010-04-01

    Biases in emotional processing and cognitions about the self are thought to play a role in the maintenance of eating disorders (EDs). However, little is known about whether these difficulties exist pre-morbidly and how they might contribute to risk. Female dieters (n=82) completed a battery of tasks designed to assess the processing of social cues (facial emotion recognition), cognitions about the self [Self-Schema Processing Task (SSPT)] and ED-specific cognitions about eating, weight and shape (emotional Stroop). The 26-item Eating Attitudes Test (EAT-26; Garner et al. 1982) was used to assess subclinical ED symptoms; this was used as an index of vulnerability within this at-risk group. Regression analyses showed that biases in the processing of both neutral and angry faces were predictive of our measure of vulnerability (EAT-26). In the self-schema task, biases in the processing of negative self descriptors previously found to be common in EDs predicted vulnerability. Biases in the processing of shape-related words on the Stroop task were also predictive; however, these biases were more important in dieters who also displayed biases in the self-schema task. We were also able to demonstrate that these biases are specific and separable from more general negative biases that could be attributed to depressive symptoms. These results suggest that specific biases in the processing of social cues, cognitions about the self, and also about eating, weight and shape information, may be important in understanding risk and preventing relapse in EDs.

  17. A systematic review of context bias in invasion biology.

    Science.gov (United States)

    Warren, Robert J; King, Joshua R; Tarsa, Charlene; Haas, Brian; Henderson, Jeremy

    2017-01-01

    The language that scientists use to frame biological invasions may reveal inherent bias-including how data are interpreted. A frequent critique of invasion biology is the use of value-laden language that may indicate context bias. Here we use a systematic study of language and interpretation in papers drawn from invasion biology to evaluate whether there is a link between the framing of papers and the interpretation of results. We also examine any trends in context bias in biological invasion research. We examined 651 peer-reviewed invasive species competition studies and implemented a rigorous systematic review to examine bias in the presentation and interpretation of native and invasive competition in invasion biology. We predicted that bias in the presentation of invasive species is increasing, as suggested by several authors, and that bias against invasive species would result in misinterpreting their competitive dominance in correlational observational studies compared to causative experimental studies. We indeed found evidence of bias in the presentation and interpretation of invasive species research; authors often introduced research with invasive species in a negative context and study results were interpreted against invasive species more in correlational studies. However, we also found a distinct decrease in those biases since the mid-2000s. Given that there have been several waves of criticism from scientists both inside and outside invasion biology, our evidence suggests that the subdiscipline has somewhat self-corrected apparent biases.

  18. Some design considerations for perpendicular biased ferrite tuners

    International Nuclear Information System (INIS)

    Enchevich, I.B.; Poirier, R.L.

    1994-10-01

    Recently remarkable progress has been achieved in the development of perpendicular biased ferrite tuned rf resonators for fast cycled synchrotrons. Compared with the broadly used parallel biased rf cavities they provide higher resonator quality factor Q. However when designing perpendicular biased cavities, special attention should be paid to the methods to provide eddy current suppression in the resonator walls, the ferrite nonlinearity influence, the generated heat removal, the fast self resonant frequency control. The prospective of a faster additional biasing system are discussed and conclusions are drawn. (author). 8 refs., 6 figs

  19. DC and AC biasing of a transition edge sensor microcalorimeter

    International Nuclear Information System (INIS)

    Cunningham, M.F.; Ullom, J.N.; Miyazaki, T.; Drury, O.; Loshak, A.; Berg, M.L. van den; Labov, S.E.

    2002-01-01

    We are developing AC-biased transition edge sensor (TES) microcalorimeters for use in large arrays with frequency-domain multiplexing. Using DC bias, we have achieved a resolution of 17 eV FWHM at 2.6 keV with a decay time of 90 μs and an effective detector diameter of 300 μm. We have successfully measured thermal pulses with a TES microcalorimeter operated with an AC bias. We present here preliminary results from a single pixel detector operated under DC and AC bias conditions

  20. Specificity and overlap of attention and memory biases in depression.

    Science.gov (United States)

    Marchetti, Igor; Everaert, Jonas; Dainer-Best, Justin; Loeys, Tom; Beevers, Christopher G; Koster, Ernst H W

    2018-01-01

    Attentional and memory biases are viewed as crucial cognitive processes underlying symptoms of depression. However, it is still unclear whether these two biases are uniquely related to depression or whether they show substantial overlap. We investigated the degree of specificity and overlap of attentional and memory biases for depressotypic stimuli in relation to depression and anxiety by means of meta-analytic commonality analysis. By including four published studies, we considered a pool of 463 healthy and subclinically depressed individuals, different experimental paradigms, and different psychological measures. Memory bias is reliably and strongly related to depression and, specifically, to symptoms of negative mood, worthlessness, feelings of failure, and pessimism. Memory bias for negative information was minimally related to anxiety. Moreover, neither attentional bias nor the overlap between attentional and memory biases were significantly related to depression. Limitations include cross-sectional nature of the study. Our study showed that, across different paradigms and psychological measures, memory bias (and not attentional bias) represents a primary mechanism in depression. Copyright © 2017 Elsevier B.V. All rights reserved.