Using the fast fourier transform in binding free energy calculations.

PubMed

Nguyen, Trung Hai; Zhou, Huan-Xiang; Minh, David D L

2018-04-30

According to implicit ligand theory, the standard binding free energy is an exponential average of the binding potential of mean force (BPMF), an exponential average of the interaction energy between the unbound ligand ensemble and a rigid receptor. Here, we use the fast Fourier transform (FFT) to efficiently evaluate BPMFs by calculating interaction energies when rigid ligand configurations from the unbound ensemble are discretely translated across rigid receptor conformations. Results for standard binding free energies between T4 lysozyme and 141 small organic molecules are in good agreement with previous alchemical calculations based on (1) a flexible complex ( R≈0.9 for 24 systems) and (2) flexible ligand with multiple rigid receptor configurations ( R≈0.8 for 141 systems). While the FFT is routinely used for molecular docking, to our knowledge this is the first time that the algorithm has been used for rigorous binding free energy calculations. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Components of Implicit Stigma against Mental Illness among Chinese Students

PubMed Central

Wang, Xiaogang; Huang, Xiting; Jackson, Todd; Chen, Ruijun

2012-01-01

Although some research has examined negative automatic aspects of attitudes toward mental illness via relatively indirect measures among Western samples, it is unclear whether negative attitudes can be automatically activated in individuals from non-Western countries. This study attempted to validate results from Western samples with Chinese college students. We first examined the three-component model of implicit stigma (negative cognition, negative affect, and discriminatory tendencies) toward mental illness with the Single Category Implicit Association Test (SC-IAT). We also explored the relationship between explicit and implicit stigma among 56 Chinese university college students. In the three separate SC-IATs and the combined SC-IAT, automatic associations between mental illness and negative descriptors were stronger relative to those with positive descriptors and the implicit effect of cognitive and affective SC-IATs were significant. Explicit and implicit measures of stigma toward mental illness were unrelated. In our sample, women's overall attitudes toward mental illness were more negative than men's were, but no gender differences were found for explicit measures. These findings suggested that implicit stigma toward mental illness exists in Chinese students, and provide some support for the three-component model of implicit stigma toward mental illness. Future studies that focus on automatic components of stigmatization and stigma-reduction in China are warranted. PMID:23029366

Effects of electrostatic interactions on ligand dissociation kinetics

NASA Astrophysics Data System (ADS)

Erbaş, Aykut; de la Cruz, Monica Olvera; Marko, John F.

2018-02-01

We study unbinding of multivalent cationic ligands from oppositely charged polymeric binding sites sparsely grafted on a flat neutral substrate. Our molecular dynamics simulations are suggested by single-molecule studies of protein-DNA interactions. We consider univalent salt concentrations spanning roughly a 1000-fold range, together with various concentrations of excess ligands in solution. To reveal the ionic effects on unbinding kinetics of spontaneous and facilitated dissociation mechanisms, we treat electrostatic interactions both at a Debye-Hückel (DH) (or implicit ions, i.e., use of an electrostatic potential with a prescribed decay length) level and by the more precise approach of considering all ionic species explicitly in the simulations. We find that the DH approach systematically overestimates unbinding rates, relative to the calculations where all ion pairs are present explicitly in solution, although many aspects of the two types of calculation are qualitatively similar. For facilitated dissociation (FD) (acceleration of unbinding by free ligands in solution) explicit-ion simulations lead to unbinding at lower free-ligand concentrations. Our simulations predict a variety of FD regimes as a function of free-ligand and ion concentrations; a particularly interesting regime is at intermediate concentrations of ligands where nonelectrostatic binding strength controls FD. We conclude that explicit-ion electrostatic modeling is an essential component to quantitatively tackle problems in molecular ligand dissociation, including nucleic-acid-binding proteins.

Physics-based scoring of protein-ligand interactions: explicit polarizability, quantum mechanics and free energies.

PubMed

Bryce, Richard A

2011-04-01

The ability to accurately predict the interaction of a ligand with its receptor is a key limitation in computer-aided drug design approaches such as virtual screening and de novo design. In this article, we examine current strategies for a physics-based approach to scoring of protein-ligand affinity, as well as outlining recent developments in force fields and quantum chemical techniques. We also consider advances in the development and application of simulation-based free energy methods to study protein-ligand interactions. Fuelled by recent advances in computational algorithms and hardware, there is the opportunity for increased integration of physics-based scoring approaches at earlier stages in computationally guided drug discovery. Specifically, we envisage increased use of implicit solvent models and simulation-based scoring methods as tools for computing the affinities of large virtual ligand libraries. Approaches based on end point simulations and reference potentials allow the application of more advanced potential energy functions to prediction of protein-ligand binding affinities. Comprehensive evaluation of polarizable force fields and quantum mechanical (QM)/molecular mechanical and QM methods in scoring of protein-ligand interactions is required, particularly in their ability to address challenging targets such as metalloproteins and other proteins that make highly polar interactions. Finally, we anticipate increasingly quantitative free energy perturbation and thermodynamic integration methods that are practical for optimization of hits obtained from screened ligand libraries.

Implicit Racial/Ethnic Bias Among Health Care Professionals and Its Influence on Health Care Outcomes: A Systematic Review.

PubMed

Hall, William J; Chapman, Mimi V; Lee, Kent M; Merino, Yesenia M; Thomas, Tainayah W; Payne, B Keith; Eng, Eugenia; Day, Steven H; Coyne-Beasley, Tamera

2015-12-01

In the United States, people of color face disparities in access to health care, the quality of care received, and health outcomes. The attitudes and behaviors of health care providers have been identified as one of many factors that contribute to health disparities. Implicit attitudes are thoughts and feelings that often exist outside of conscious awareness, and thus are difficult to consciously acknowledge and control. These attitudes are often automatically activated and can influence human behavior without conscious volition. We investigated the extent to which implicit racial/ethnic bias exists among health care professionals and examined the relationships between health care professionals' implicit attitudes about racial/ethnic groups and health care outcomes. To identify relevant studies, we searched 10 computerized bibliographic databases and used a reference harvesting technique. We assessed eligibility using double independent screening based on a priori inclusion criteria. We included studies if they sampled existing health care providers or those in training to become health care providers, measured and reported results on implicit racial/ethnic bias, and were written in English. We included a total of 15 studies for review and then subjected them to double independent data extraction. Information extracted included the citation, purpose of the study, use of theory, study design, study site and location, sampling strategy, response rate, sample size and characteristics, measurement of relevant variables, analyses performed, and results and findings. We summarized study design characteristics, and categorized and then synthesized substantive findings. Almost all studies used cross-sectional designs, convenience sampling, US participants, and the Implicit Association Test to assess implicit bias. Low to moderate levels of implicit racial/ethnic bias were found among health care professionals in all but 1 study. These implicit bias scores are similar to those in the general population. Levels of implicit bias against Black, Hispanic/Latino/Latina, and dark-skinned people were relatively similar across these groups. Although some associations between implicit bias and health care outcomes were nonsignificant, results also showed that implicit bias was significantly related to patient-provider interactions, treatment decisions, treatment adherence, and patient health outcomes. Implicit attitudes were more often significantly related to patient-provider interactions and health outcomes than treatment processes. Most health care providers appear to have implicit bias in terms of positive attitudes toward Whites and negative attitudes toward people of color. Future studies need to employ more rigorous methods to examine the relationships between implicit bias and health care outcomes. Interventions targeting implicit attitudes among health care professionals are needed because implicit bias may contribute to health disparities for people of color.

Implicit Racial/Ethnic Bias Among Health Care Professionals and Its Influence on Health Care Outcomes: A Systematic Review

PubMed Central

Hall, William J.; Lee, Kent M.; Merino, Yesenia M.; Thomas, Tainayah W.; Payne, B. Keith; Eng, Eugenia; Day, Steven H.; Coyne-Beasley, Tamera

2015-01-01

Background. In the United States, people of color face disparities in access to health care, the quality of care received, and health outcomes. The attitudes and behaviors of health care providers have been identified as one of many factors that contribute to health disparities. Implicit attitudes are thoughts and feelings that often exist outside of conscious awareness, and thus are difficult to consciously acknowledge and control. These attitudes are often automatically activated and can influence human behavior without conscious volition. Objectives. We investigated the extent to which implicit racial/ethnic bias exists among health care professionals and examined the relationships between health care professionals’ implicit attitudes about racial/ethnic groups and health care outcomes. Search Methods. To identify relevant studies, we searched 10 computerized bibliographic databases and used a reference harvesting technique. Selection Criteria. We assessed eligibility using double independent screening based on a priori inclusion criteria. We included studies if they sampled existing health care providers or those in training to become health care providers, measured and reported results on implicit racial/ethnic bias, and were written in English. Data Collection and Analysis. We included a total of 15 studies for review and then subjected them to double independent data extraction. Information extracted included the citation, purpose of the study, use of theory, study design, study site and location, sampling strategy, response rate, sample size and characteristics, measurement of relevant variables, analyses performed, and results and findings. We summarized study design characteristics, and categorized and then synthesized substantive findings. Main Results. Almost all studies used cross-sectional designs, convenience sampling, US participants, and the Implicit Association Test to assess implicit bias. Low to moderate levels of implicit racial/ethnic bias were found among health care professionals in all but 1 study. These implicit bias scores are similar to those in the general population. Levels of implicit bias against Black, Hispanic/Latino/Latina, and dark-skinned people were relatively similar across these groups. Although some associations between implicit bias and health care outcomes were nonsignificant, results also showed that implicit bias was significantly related to patient–provider interactions, treatment decisions, treatment adherence, and patient health outcomes. Implicit attitudes were more often significantly related to patient–provider interactions and health outcomes than treatment processes. Conclusions. Most health care providers appear to have implicit bias in terms of positive attitudes toward Whites and negative attitudes toward people of color. Future studies need to employ more rigorous methods to examine the relationships between implicit bias and health care outcomes. Interventions targeting implicit attitudes among health care professionals are needed because implicit bias may contribute to health disparities for people of color. PMID:26469668

Ligand Docking to Intermediate and Close-To-Bound Conformers Generated by an Elastic Network Model Based Algorithm for Highly Flexible Proteins

PubMed Central

Kurkcuoglu, Zeynep; Doruker, Pemra

2016-01-01

Incorporating receptor flexibility in small ligand-protein docking still poses a challenge for proteins undergoing large conformational changes. In the absence of bound structures, sampling conformers that are accessible by apo state may facilitate docking and drug design studies. For this aim, we developed an unbiased conformational search algorithm, by integrating global modes from elastic network model, clustering and energy minimization with implicit solvation. Our dataset consists of five diverse proteins with apo to complex RMSDs 4.7–15 Å. Applying this iterative algorithm on apo structures, conformers close to the bound-state (RMSD 1.4–3.8 Å), as well as the intermediate states were generated. Dockings to a sequence of conformers consisting of a closed structure and its “parents” up to the apo were performed to compare binding poses on different states of the receptor. For two periplasmic binding proteins and biotin carboxylase that exhibit hinge-type closure of two dynamics domains, the best pose was obtained for the conformer closest to the bound structure (ligand RMSDs 1.5–2 Å). In contrast, the best pose for adenylate kinase corresponded to an intermediate state with partially closed LID domain and open NMP domain, in line with recent studies (ligand RMSD 2.9 Å). The docking of a helical peptide to calmodulin was the most challenging case due to the complexity of its 15 Å transition, for which a two-stage procedure was necessary. The technique was first applied on the extended calmodulin to generate intermediate conformers; then peptide docking and a second generation stage on the complex were performed, which in turn yielded a final peptide RMSD of 2.9 Å. Our algorithm is effective in producing conformational states based on the apo state. This study underlines the importance of such intermediate states for ligand docking to proteins undergoing large transitions. PMID:27348230

ICCS 2009 User Guide for the International Database. Supplement 4: ICCS 2009 Sampling Stratification Information

ERIC Educational Resources Information Center

Brese, Falk; Jung, Michael; Mirazchiyski, Plamen; Schulz, Wolfram; Zuehlke, Olaf

2011-01-01

This supplement contains documentation on the explicit and implicit stratification variables included in the International Civic and Citizenship Education Study (ICCS) 2009 data files. The explicit strata are smaller sampling frames, created from the national sampling frames, from which national samples of schools were drawn. The implicit strata…

Implicit Social Biases in People with Autism

PubMed Central

Birmingham, Elina; Stanley, Damian; Nair, Remya; Adolphs, Ralph

2015-01-01

Implicit social biases are ubiquitous and are known to influence social behavior. A core diagnostic criterion of Autism Spectrum Disorder (ASD) is abnormal social behavior. Here we investigated the extent to which individuals with ASD might show a specific attenuation of implicit social biases, using the Implicit Association Test (IAT) across Social (gender, race) and Nonsocial (flowers/insect, shoes) categories. High-functioning adults with ASD showed intact but reduced IAT effects relative to healthy controls. Importantly, we observed no selective attenuation of implicit social (vs. nonsocial) biases in our ASD population. To extend these results, we collected data from a large online sample of the general population, and explored correlations between autistic traits and IAT effects. No associations were found between autistic traits and IAT effects for any of the categories tested in our online sample. Taken together, these results suggest that implicit social biases, as measured by the IAT, are largely intact in ASD. PMID:26386014

Evaluation of Hydration Free Energy by Level-Set Variational Implicit-Solvent Model with Coulomb-Field Approximation.

PubMed

Guo, Zuojun; Li, Bo; Dzubiella, Joachim; Cheng, Li-Tien; McCammon, J Andrew; Che, Jianwei

2013-03-12

In this article, we systematically apply a novel implicit-solvent model, the variational implicit-solvent model (VISM) together with the Coulomb-Field Approximation (CFA), to calculate the hydration free energy of a large set of small organic molecules. Because these molecules have been studied in detail by molecular dynamics simulations and other implicit-solvent models, they provide a good benchmark for evaluating the performance of VISM-CFA. With all-atom Amber force field parameters, VISM-CFA is able to reproduce well not only the experimental and MD simulated total hydration free energy but also the polar and nonpolar contributions individually. The correlation between VISM-CFA and experiments is R 2 = 0.763 for the total hydration free energy, with a root-mean-square deviation (RMSD) of 1.83 kcal/mol, and the correlation to results from TIP3P explicit water MD simulations is R 2 = 0.839 with a RMSD = 1.36 kcal/mol. In addition, we demonstrate that VISM captures dewetting phenomena in the p53/MDM2 complex and hydrophobic characteristics in the system. This work demonstrates that the level-set VISM-CFA can be used to study the energetic behavior of realistic molecular systems with complicated geometries in solvation, protein-ligand binding, protein-protein association, and protein folding processes.

PIRLS 2011 User Guide for the International Database. Supplement 4: PIRLS 2011 Sampling Stratification Information

ERIC Educational Resources Information Center

Foy, Pierre, Ed.; Drucker, Kathleen T., Ed.

2013-01-01

This supplement contains documentation on the explicit and implicit stratification variables included in the PIRLS 2011 data files. The explicit strata are smaller sampling frames, created from the national sampling frames, from which national samples of schools were drawn. The implicit strata are nested within the explicit strata, and were used…

TIMSS 2011 User Guide for the International Database. Supplement 4: TIMSS 2011 Sampling Stratification Information

ERIC Educational Resources Information Center

Foy, Pierre, Ed.; Arora, Alka, Ed.; Stanco, Gabrielle M., Ed.

2013-01-01

This supplement contains documentation on the explicit and implicit stratification variables included in the TIMSS 2011 data files. The explicit strata are smaller sampling frames, created from the national sampling frames, from which national samples of schools were drawn. The implicit strata are nested within the explicit strata, and were used…

Implicit and explicit weight bias in a national sample of 4,732 medical students: the medical student CHANGES study.

PubMed

Phelan, Sean M; Dovidio, John F; Puhl, Rebecca M; Burgess, Diana J; Nelson, David B; Yeazel, Mark W; Hardeman, Rachel; Perry, Sylvia; van Ryn, Michelle

2014-04-01

To examine the magnitude of explicit and implicit weight biases compared to biases against other groups; and identify student factors predicting bias in a large national sample of medical students. A web-based survey was completed by 4,732 1st year medical students from 49 medical schools as part of a longitudinal study of medical education. The survey included a validated measure of implicit weight bias, the implicit association test, and 2 measures of explicit bias: a feeling thermometer and the anti-fat attitudes test. A majority of students exhibited implicit (74%) and explicit (67%) weight bias. Implicit weight bias scores were comparable to reported bias against racial minorities. Explicit attitudes were more negative toward obese people than toward racial minorities, gays, lesbians, and poor people. In multivariate regression models, implicit and explicit weight bias was predicted by lower BMI, male sex, and non-Black race. Either implicit or explicit bias was also predicted by age, SES, country of birth, and specialty choice. Implicit and explicit weight bias is common among 1st year medical students, and varies across student factors. Future research should assess implications of biases and test interventions to reduce their impact. Copyright © 2013 The Obesity Society.

Biophysical Characterisation of Neuroglobin of the Icefish, a Natural Knockout for Hemoglobin and Myoglobin. Comparison with Human Neuroglobin

PubMed Central

Giordano, Daniela; Boron, Ignacio; Abbruzzetti, Stefania; Van Leuven, Wendy; Nicoletti, Francesco P.; Forti, Flavio; Bruno, Stefano; Cheng, C-H. Christina; Moens, Luc; di Prisco, Guido; Nadra, Alejandro D.; Estrin, Darío; Smulevich, Giulietta; Dewilde, Sylvia; Viappiani, Cristiano; Verde, Cinzia

2012-01-01

The Antarctic icefish Chaenocephalus aceratus lacks the globins common to most vertebrates, hemoglobin and myoglobin, but has retained neuroglobin in the brain. This conserved globin has been cloned, over-expressed and purified. To highlight similarities and differences, the structural features of the neuroglobin of this colourless-blooded fish were compared with those of the well characterised human neuroglobin as well as with the neuroglobin from the retina of the red blooded, hemoglobin and myoglobin-containing, closely related Antarctic notothenioid Dissostichus mawsoni. A detailed structural and functional analysis of the two Antarctic fish neuroglobins was carried out by UV-visible and Resonance Raman spectroscopies, molecular dynamics simulations and laser-flash photolysis. Similar to the human protein, Antarctic fish neuroglobins can reversibly bind oxygen and CO in the Fe2+ form, and show six-coordination by distal His in the absence of exogenous ligands. A very large and structured internal cavity, with discrete docking sites, was identified in the modelled three-dimensional structures of the Antarctic neuroglobins. Estimate of the free-energy barriers from laser-flash photolysis and Implicit Ligand Sampling showed that the cavities are accessible from the solvent in both proteins. Comparison of structural and functional properties suggests that the two Antarctic fish neuroglobins most likely preserved and possibly improved the function recently proposed for human neuroglobin in ligand multichemistry. Despite subtle differences, the adaptation of Antarctic fish neuroglobins does not seem to parallel the dramatic adaptation of the oxygen carrying globins, hemoglobin and myoglobin, in the same organisms. PMID:23226490

CHARMM-GUI 10 Years for Biomolecular Modeling and Simulation

PubMed Central

Jo, Sunhwan; Cheng, Xi; Lee, Jumin; Kim, Seonghoon; Park, Sang-Jun; Patel, Dhilon S.; Beaven, Andrew H.; Lee, Kyu Il; Rui, Huan; Roux, Benoît; MacKerell, Alexander D.; Klauda, Jeffrey B.; Qi, Yifei

2017-01-01

CHARMM-GUI, http://www.charmm-gui.org, is a web-based graphical user interface that prepares complex biomolecular systems for molecular simulations. CHARMM-GUI creates input files for a number of programs including CHARMM, NAMD, GROMACS, AMBER, GENESIS, LAMMPS, Desmond, OpenMM, and CHARMM/OpenMM. Since its original development in 2006, CHARMM-GUI has been widely adopted for various purposes and now contains a number of different modules designed to set up a broad range of simulations: (1) PDB Reader & Manipulator, Glycan Reader, and Ligand Reader & Modeler for reading and modifying molecules; (2) Quick MD Simulator, Membrane Builder, Nanodisc Builder, HMMM Builder, Monolayer Builder, Micelle Builder, and Hex Phase Builder for building all-atom simulation systems in various environments; (3) PACE CG Builder and Martini Maker for building coarse-grained simulation systems; (4) DEER Facilitator and MDFF/xMDFF Utilizer for experimentally guided simulations; (5) Implicit Solvent Modeler, PBEQ-Solver, and GCMC/BD Ion Simulator for implicit solvent related calculations; (6) Ligand Binder for ligand solvation and binding free energy simulations; and (7) Drude Prepper for preparation of simulations with the CHARMM Drude polarizable force field. Recently, new modules have been integrated into CHARMM-GUI, such as Glycolipid Modeler for generation of various glycolipid structures, and LPS Modeler for generation of lipopolysaccharide structures from various Gram-negative bacteria. These new features together with existing modules are expected to facilitate advanced molecular modeling and simulation thereby leading to an improved understanding of the molecular details of the structure and dynamics of complex biomolecular systems. Here, we briefly review these capabilities and discuss potential future directions in the CHARMM-GUI development project. PMID:27862047

CHARMM-GUI 10 years for biomolecular modeling and simulation.

PubMed

Jo, Sunhwan; Cheng, Xi; Lee, Jumin; Kim, Seonghoon; Park, Sang-Jun; Patel, Dhilon S; Beaven, Andrew H; Lee, Kyu Il; Rui, Huan; Park, Soohyung; Lee, Hui Sun; Roux, Benoît; MacKerell, Alexander D; Klauda, Jeffrey B; Qi, Yifei; Im, Wonpil

2017-06-05

CHARMM-GUI, http://www.charmm-gui.org, is a web-based graphical user interface that prepares complex biomolecular systems for molecular simulations. CHARMM-GUI creates input files for a number of programs including CHARMM, NAMD, GROMACS, AMBER, GENESIS, LAMMPS, Desmond, OpenMM, and CHARMM/OpenMM. Since its original development in 2006, CHARMM-GUI has been widely adopted for various purposes and now contains a number of different modules designed to set up a broad range of simulations: (1) PDB Reader & Manipulator, Glycan Reader, and Ligand Reader & Modeler for reading and modifying molecules; (2) Quick MD Simulator, Membrane Builder, Nanodisc Builder, HMMM Builder, Monolayer Builder, Micelle Builder, and Hex Phase Builder for building all-atom simulation systems in various environments; (3) PACE CG Builder and Martini Maker for building coarse-grained simulation systems; (4) DEER Facilitator and MDFF/xMDFF Utilizer for experimentally guided simulations; (5) Implicit Solvent Modeler, PBEQ-Solver, and GCMC/BD Ion Simulator for implicit solvent related calculations; (6) Ligand Binder for ligand solvation and binding free energy simulations; and (7) Drude Prepper for preparation of simulations with the CHARMM Drude polarizable force field. Recently, new modules have been integrated into CHARMM-GUI, such as Glycolipid Modeler for generation of various glycolipid structures, and LPS Modeler for generation of lipopolysaccharide structures from various Gram-negative bacteria. These new features together with existing modules are expected to facilitate advanced molecular modeling and simulation thereby leading to an improved understanding of the structure and dynamics of complex biomolecular systems. Here, we briefly review these capabilities and discuss potential future directions in the CHARMM-GUI development project. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Attitudes toward Overweight Individuals among Fitness Center Employees: An Examination of Contextual Effects

ERIC Educational Resources Information Center

Dimmock, James A.; Hallett, Bree E.; Grove, J. Robert

2009-01-01

Our study assessed implicit and explicit evaluations of overweight individuals among a sample of fitness center employees (N = 70). Participants completed a general demographics questionnaire and an explicit, self-report Antifat Attitudes Test (AFAT). Participants also completed two Implicit Association Tests (IATs) to measure implicit attitudes…

Naproxen Interferes with the Assembly of Aβ Oligomers Implicated in Alzheimer's Disease

PubMed Central

Kim, Seongwon; Chang, Wenling E.; Kumar, Rashmi; Klimov, Dmitri K.

2011-01-01

Experimental and epidemiological studies have shown that the nonsteroidal antiinflammatory drug naproxen may be useful in the treatment of Alzheimer's disease. To investigate the interactions of naproxen with Aβ dimers, which are the smallest cytotoxic aggregated Aβ peptide species, we use united atom implicit solvent model and exhaustive replica exchange molecular dynamics. We show that naproxen ligands bind to Aβ dimer and penetrate its volume interfering with the interpeptide interactions. As a result naproxen induces a destabilizing effect on Aβ dimer. By comparing the free-energy landscapes of naproxen interactions with Aβ dimers and fibrils, we conclude that this ligand has stronger antiaggregation potential against Aβ fibrils rather than against dimers. The analysis of naproxen binding energetics shows that the location of ligand binding sites in Aβ dimer is dictated by the Aβ amino acid sequence. Comparison of the in silico findings with experimental observations reveals potential limitations of naproxen as an effective therapeutic agent in the treatment of Alzheimer's disease. PMID:21504739

Stereotypical images and implicit weight bias in overweight/obese people

PubMed Central

Hinman, Nova G.; Burmeister, Jacob M.; Hoffmann, Debra A.; Ashrafioun, Lisham; Koball, Afton M.

2013-01-01

Purpose In this brief report, an unanswered question in implicit weight bias research is addressed: Is weight bias stronger when obese and thin people are pictured engaging in stereotype consistent behaviors (e.g., obese—watching TV/eating junk food; thin—exercising/eating healthy) as opposed to the converse? Methods Implicit Associations Test (IAT) data were collected from two samples of overweight/obese adults participating in weight loss treatment. Both samples completed two IATs. In one IAT, obese and thin people were pictured engaging in stereotype consistent behaviors (e.g., obese—watching TV/eating junk food; thin—exercising/eating healthy). In the second IAT, obese and thin people were pictured engaging in stereotype inconsistent behaviors (e.g., obese—exercising/eating healthy; thin—watching TV/eating junk food). Results Implicit weight bias was evident regardless of whether participants viewed stereotype consistent or inconsistent pictures. However, implicit bias was significantly stronger for stereotype consistent compared to stereotype inconsistent images. Conclusion Implicit anti-fat attitudes may be connected to the way in which people with obesity are portrayed. PMID:24057679

Gambling and Sport: Implicit Association and Explicit Intention Among Underage Youth.

PubMed

Li, En; Langham, Erika; Browne, Matthew; Rockloff, Matthew; Thorne, Hannah

2018-03-23

This study examined whether an implicit association existed between gambling and sport among underage youth in Australia, and whether this implicit association could shape their explicit intention to gamble. A sample of 14-17 year old Australian participants completed two phases of tasks, including an implicit association test based online experiment, and a post-experiment online survey. The results supported the existence of an implicit association between gambling and sport among the participants. This implicit association became stronger when they saw sport-relevant (vs. sport-irrelevant) gambling logos, or gambling-relevant (vs. gambling-irrelevant) sport names. In addition, this implicit association was positively related to the amount of sport viewing, but only among those participants who had more favorable gambling attitudes. Lastly, gambling attitudes and advertising knowledge, rather than the implicit association, turned out to be significant predictors of the explicit intention to gamble.

Evaluation of Several Two-Step Scoring Functions Based on Linear Interaction Energy, Effective Ligand Size, and Empirical Pair Potentials for Prediction of Protein-Ligand Binding Geometry and Free Energy

PubMed Central

Rahaman, Obaidur; Estrada, Trilce P.; Doren, Douglas J.; Taufer, Michela; Brooks, Charles L.; Armen, Roger S.

2011-01-01

The performance of several two-step scoring approaches for molecular docking were assessed for their ability to predict binding geometries and free energies. Two new scoring functions designed for “step 2 discrimination” were proposed and compared to our CHARMM implementation of the linear interaction energy (LIE) approach using the Generalized-Born with Molecular Volume (GBMV) implicit solvation model. A scoring function S1 was proposed by considering only “interacting” ligand atoms as the “effective size” of the ligand, and extended to an empirical regression-based pair potential S2. The S1 and S2 scoring schemes were trained and five-fold cross validated on a diverse set of 259 protein-ligand complexes from the Ligand Protein Database (LPDB). The regression-based parameters for S1 and S2 also demonstrated reasonable transferability in the CSARdock 2010 benchmark using a new dataset (NRC HiQ) of diverse protein-ligand complexes. The ability of the scoring functions to accurately predict ligand geometry was evaluated by calculating the discriminative power (DP) of the scoring functions to identify native poses. The parameters for the LIE scoring function with the optimal discriminative power (DP) for geometry (step 1 discrimination) were found to be very similar to the best-fit parameters for binding free energy over a large number of protein-ligand complexes (step 2 discrimination). Reasonable performance of the scoring functions in enrichment of active compounds in four different protein target classes established that the parameters for S1 and S2 provided reasonable accuracy and transferability. Additional analysis was performed to definitively separate scoring function performance from molecular weight effects. This analysis included the prediction of ligand binding efficiencies for a subset of the CSARdock NRC HiQ dataset where the number of ligand heavy atoms ranged from 17 to 35. This range of ligand heavy atoms is where improved accuracy of predicted ligand efficiencies is most relevant to real-world drug design efforts. PMID:21644546

Evaluation of several two-step scoring functions based on linear interaction energy, effective ligand size, and empirical pair potentials for prediction of protein-ligand binding geometry and free energy.

PubMed

Rahaman, Obaidur; Estrada, Trilce P; Doren, Douglas J; Taufer, Michela; Brooks, Charles L; Armen, Roger S

2011-09-26

The performances of several two-step scoring approaches for molecular docking were assessed for their ability to predict binding geometries and free energies. Two new scoring functions designed for "step 2 discrimination" were proposed and compared to our CHARMM implementation of the linear interaction energy (LIE) approach using the Generalized-Born with Molecular Volume (GBMV) implicit solvation model. A scoring function S1 was proposed by considering only "interacting" ligand atoms as the "effective size" of the ligand and extended to an empirical regression-based pair potential S2. The S1 and S2 scoring schemes were trained and 5-fold cross-validated on a diverse set of 259 protein-ligand complexes from the Ligand Protein Database (LPDB). The regression-based parameters for S1 and S2 also demonstrated reasonable transferability in the CSARdock 2010 benchmark using a new data set (NRC HiQ) of diverse protein-ligand complexes. The ability of the scoring functions to accurately predict ligand geometry was evaluated by calculating the discriminative power (DP) of the scoring functions to identify native poses. The parameters for the LIE scoring function with the optimal discriminative power (DP) for geometry (step 1 discrimination) were found to be very similar to the best-fit parameters for binding free energy over a large number of protein-ligand complexes (step 2 discrimination). Reasonable performance of the scoring functions in enrichment of active compounds in four different protein target classes established that the parameters for S1 and S2 provided reasonable accuracy and transferability. Additional analysis was performed to definitively separate scoring function performance from molecular weight effects. This analysis included the prediction of ligand binding efficiencies for a subset of the CSARdock NRC HiQ data set where the number of ligand heavy atoms ranged from 17 to 35. This range of ligand heavy atoms is where improved accuracy of predicted ligand efficiencies is most relevant to real-world drug design efforts.

Is Implicit Motor Learning Preserved after Stroke? A Systematic Review with Meta-Analysis

PubMed Central

Kal, E.; Winters, M.; van der Kamp, J.; Houdijk, H.; Groet, E.; van Bennekom, C.; Scherder, E.

2016-01-01

Many stroke patients experience difficulty with performing dual-tasks. A promising intervention to target this issue is implicit motor learning, as it should enhance patients’ automaticity of movement. Yet, although it is often thought that implicit motor learning is preserved post-stroke, evidence for this claim has not been systematically analysed yet. Therefore, we systematically reviewed whether implicit motor learning is preserved post-stroke, and whether patients benefit more from implicit than from explicit motor learning. We comprehensively searched conventional (MEDLINE, Cochrane, Embase, PEDro, PsycINFO) and grey literature databases (BIOSIS, Web of Science, OpenGrey, British Library, trial registries) for relevant reports. Two independent reviewers screened reports, extracted data, and performed a risk of bias assessment. Overall, we included 20 out of the 2177 identified reports that allow for a succinct evaluation of implicit motor learning. Of these, only 1 study investigated learning on a relatively complex, whole-body (balance board) task. All 19 other studies concerned variants of the serial-reaction time paradigm, with most of these focusing on learning with the unaffected hand (N = 13) rather than the affected hand or both hands (both: N = 4). Four of the 20 studies compared explicit and implicit motor learning post-stroke. Meta-analyses suggest that patients with stroke can learn implicitly with their unaffected side (mean difference (MD) = 69 ms, 95% CI[45.1, 92.9], p < .00001), but not with their affected side (standardized MD = -.11, 95% CI[-.45, .25], p = .56). Finally, implicit motor learning seemed equally effective as explicit motor learning post-stroke (SMD = -.54, 95% CI[-1.37, .29], p = .20). However, overall, the high risk of bias, small samples, and limited clinical relevance of most studies make it impossible to draw reliable conclusions regarding the effect of implicit motor learning strategies post-stroke. High quality studies with larger samples are warranted to test implicit motor learning in clinically relevant contexts. PMID:27992442

The effect of social exclusion on state paranoia and explicit and implicit self-esteem in a non-clinical sample.

PubMed

Stewart, C; Rogers, F; Pilch, M; Stewart, I; Barnes-Holmes, Y; Westermann, S

2017-12-01

The relationship between self-esteem and paranoia may be influenced by social stress. This study aimed to replicate previous research on the impact ofsocial exclusion on paranoia and self-esteem in a non-clinical sample and to extend this work by examining the effect of exclusion on self-esteem at the 'implicit' level. Non-clinical participants (N = 85) were randomly allocated to the Inclusion or Exclusion condition of a virtual ball-toss game ('Cyberball'). They completed self-reportmeasures of state paranoia and self-esteem, and two implicit measures of self-esteem - theImplicit Association Task (IAT) and Implicit Relational Assessment Procedure (IRAP) -prior to and after exposure to Cyberball. Social exclusion increased state paranoia. This effect was moderated by distress associated with trait paranoia. Exclusion was also associated with decreased self-reported self-esteem, as well as reduced implicit self-esteem on the IAT. Changes in self-reported self-esteem were associated with state paranoia at post-Cyberball. The IRAP indicated that reductions in implicit self-esteem may be due to increases in 'Me-Negative' and 'Others-Positive' biases (rather than reductions in 'Me-Positive' bias). The current study involved a non-clinical sample and so findings cannot be generalized to clinical paranoia. These findings are consistent with previous evidence that paranoia is associated with negative self-evaluations, whereas positive self-evaluations can persist in paranoia. They also provide support for the suggestion that investigations of self-esteem in paranoia should extend beyond global self-esteem and might benefit from a distinction between positive and negative components. Copyright © 2017 Elsevier Ltd. All rights reserved.

Implicit spiritual assessment: an alternative approach for assessing client spirituality.

PubMed

Hodge, David R

2013-07-01

To provide optimal services, a spiritual assessment is often administered to understand the intersection between clients' spirituality and service provision. Traditional assessment approaches, however, may be ineffective with clients who are uncomfortable with spiritual language or who are otherwise hesitant to discuss spirituality overtly. This article orients readers to an implicit spiritual assessment, an alternative approach that may be more valid with such clients. The process of administering an implicit assessment is discussed, sample questions are provided to help operationalize this approach, and suggestions are offered to integrate an implicit assessment with more traditional assessment approaches. By using terminology that is implicitly spiritual in nature, an implicit assessment enables practitioners to identify and operationalize dimensions of clients' experience that may be critical to effective service provision but would otherwise be overlooked.

Uncertainty in sample estimates and the implicit loss function for soil information.

NASA Astrophysics Data System (ADS)

Lark, Murray

2015-04-01

One significant challenge in the communication of uncertain information is how to enable the sponsors of sampling exercises to make a rational choice of sample size. One way to do this is to compute the value of additional information given the loss function for errors. The loss function expresses the costs that result from decisions made using erroneous information. In certain circumstances, such as remediation of contaminated land prior to development, loss functions can be computed and used to guide rational decision making on the amount of resource to spend on sampling to collect soil information. In many circumstances the loss function cannot be obtained prior to decision making. This may be the case when multiple decisions may be based on the soil information and the costs of errors are hard to predict. The implicit loss function is proposed as a tool to aid decision making in these circumstances. Conditional on a logistical model which expresses costs of soil sampling as a function of effort, and statistical information from which the error of estimates can be modelled as a function of effort, the implicit loss function is the loss function which makes a particular decision on effort rational. In this presentation the loss function is defined and computed for a number of arbitrary decisions on sampling effort for a hypothetical soil monitoring problem. This is based on a logistical model of sampling cost parameterized from a recent geochemical survey of soil in Donegal, Ireland and on statistical parameters estimated with the aid of a process model for change in soil organic carbon. It is shown how the implicit loss function might provide a basis for reflection on a particular choice of sample size by comparing it with the values attributed to soil properties and functions. Scope for further research to develop and apply the implicit loss function to help decision making by policy makers and regulators is then discussed.

Effects of the Hydroxyl Group on Phenyl Based Ligand/ERRγ Protein Binding

PubMed Central

2015-01-01

Bisphenol-A (4,4′-dihydroxy-2,2-diphenylpropane, BPA, or BPA-A) and its derivatives, when exposed to humans, may affect functions of multiple organs by specific binding to the human estrogen-related receptor γ (ERRγ). We carried out atomistic molecular dynamics (MD) simulations of three ligand compounds including BPA-A, 4-α-cumylphenol (BPA-C), and 2,2-diphenylpropane (BPA-D) binding to the ligand binding domain (LBD) of a human ERRγ to study the structures and energies associated with the binding. We used the implicit Molecular Mechanics/Poisson–Boltzmann Surface Area (MM/PBSA) method to estimate the free energies of binding for the phenyl based compound/ERRγ systems. The addition of hydroxyl groups to the aromatic ring had only a minor effect on binding structures and a significant effect on ligand/protein binding energy in an aqueous solution. Free binding energies of BPA-D to the ERRγ were found to be considerably less than those of BPA-A and BPA-C to the ERRγ. These results are well correlated with those from experiments where no binding affinities were determined in the BPA-D/ERRγ complex. No conformational change was observed for the helix 12 (H-12) of ERRγ upon binding of these compounds preserving an active transcriptional conformation state. PMID:25098505

Are implicit self-esteem measures valid for assessing individual and cultural differences?

PubMed

Falk, Carl F; Heine, Steven J; Takemura, Kosuke; Zhang, Cathy X J; Hsu, Chih-Wei

2015-02-01

Our research utilized two popular theoretical conceptualizations of implicit self-esteem: 1) implicit self-esteem as a global automatic reaction to the self; and 2) implicit self-esteem as a context/domain specific construct. Under this framework, we present an extensive search for implicit self-esteem measure validity among different cultural groups (Study 1) and under several experimental manipulations (Study 2). In Study 1, Euro-Canadians (N = 107), Asian-Canadians (N = 187), and Japanese (N = 112) completed a battery of implicit self-esteem, explicit self-esteem, and criterion measures. Included implicit self-esteem measures were either popular or provided methodological improvements upon older methods. Criterion measures were sampled from previous research on implicit self-esteem and included self-report and independent ratings. In Study 2, Americans (N = 582) completed a shorter battery of these same types of measures under either a control condition, an explicit prime meant to activate the self-concept in a particular context, or prime meant to activate self-competence related implicit attitudes. Across both studies, explicit self-esteem measures far outperformed implicit self-esteem measures in all cultural groups and under all experimental manipulations. Implicit self-esteem measures are not valid for individual or cross-cultural comparisons. We speculate that individuals may not form implicit associations with the self as an attitudinal object. © 2013 Wiley Periodicals, Inc.

Explicit and implicit assessment of gender roles.

PubMed

Fernández, Juan; Quiroga, M Ángeles; Escorial, Sergio; Privado, Jesús

2014-05-01

Gender roles have been assessed by explicit measures and, recently, by implicit measures. In the former case, the theoretical assumptions have been questioned by empirical results. To solve this contradiction, we carried out two concatenated studies based on a relatively well-founded theoretical and empirical approach. The first study was designed to obtain a sample of genderized activities of the domestic sphere by means of an explicit assessment. Forty-two raters (22 women and 20 men, balanced on age, sex, and level of education) took part as raters. In the second study, an implicit assessment of gender roles was carried out, focusing on the response time given to the sample activities obtained from the first study. A total of 164 adults (90 women and 74 men, mean age = 43), with experience in living with a partner and balanced on age, sex, and level of education, participated. Taken together, results show that explicit and implicit assessment converge. The current social reality shows that there is still no equity in some gender roles in the domestic sphere. These consistent results show considerable theoretical and empirical robustness, due to the double implicit and explicit assessment.

A general and fast scoring function for protein-ligand interactions: a simplified potential approach.

PubMed

Muegge, I; Martin, Y C

1999-03-11

A fast, simplified potential-based approach is presented that estimates the protein-ligand binding affinity based on the given 3D structure of a protein-ligand complex. This general, knowledge-based approach exploits structural information of known protein-ligand complexes extracted from the Brookhaven Protein Data Bank and converts it into distance-dependent Helmholtz free interaction energies of protein-ligand atom pairs (potentials of mean force, PMF). The definition of an appropriate reference state and the introduction of a correction term accounting for the volume taken by the ligand were found to be crucial for deriving the relevant interaction potentials that treat solvation and entropic contributions implicitly. A significant correlation between experimental binding affinities and computed score was found for sets of diverse protein-ligand complexes and for sets of different ligands bound to the same target. For 77 protein-ligand complexes taken from the Brookhaven Protein Data Bank, the calculated score showed a standard deviation from observed binding affinities of 1.8 log Ki units and an R2 value of 0.61. The best results were obtained for the subset of 16 serine protease complexes with a standard deviation of 1.0 log Ki unit and an R2 value of 0.86. A set of 33 inhibitors modeled into a crystal structure of HIV-1 protease yielded a standard deviation of 0.8 log Ki units from measured inhibition constants and an R2 value of 0.74. In contrast to empirical scoring functions that show similar or sometimes better correlation with observed binding affinities, our method does not involve deriving specific parameters that fit the observed binding affinities of protein-ligand complexes of a given training set. We compared the performance of the PMF score, Böhm's score (LUDI), and the SMOG score for eight different test sets of protein-ligand complexes. It was found that for the majority of test sets the PMF score performs best. The strength of the new approach presented here lies in its generality as no knowledge about measured binding affinities is needed to derive atomic interaction potentials. The use of the new scoring function in docking studies is outlined.

KECSA-Movable Type Implicit Solvation Model (KMTISM)

PubMed Central

2015-01-01

Computation of the solvation free energy for chemical and biological processes has long been of significant interest. The key challenges to effective solvation modeling center on the choice of potential function and configurational sampling. Herein, an energy sampling approach termed the “Movable Type” (MT) method, and a statistical energy function for solvation modeling, “Knowledge-based and Empirical Combined Scoring Algorithm” (KECSA) are developed and utilized to create an implicit solvation model: KECSA-Movable Type Implicit Solvation Model (KMTISM) suitable for the study of chemical and biological systems. KMTISM is an implicit solvation model, but the MT method performs energy sampling at the atom pairwise level. For a specific molecular system, the MT method collects energies from prebuilt databases for the requisite atom pairs at all relevant distance ranges, which by its very construction encodes all possible molecular configurations simultaneously. Unlike traditional statistical energy functions, KECSA converts structural statistical information into categorized atom pairwise interaction energies as a function of the radial distance instead of a mean force energy function. Within the implicit solvent model approximation, aqueous solvation free energies are then obtained from the NVT ensemble partition function generated by the MT method. Validation is performed against several subsets selected from the Minnesota Solvation Database v2012. Results are compared with several solvation free energy calculation methods, including a one-to-one comparison against two commonly used classical implicit solvation models: MM-GBSA and MM-PBSA. Comparison against a quantum mechanics based polarizable continuum model is also discussed (Cramer and Truhlar’s Solvation Model 12). PMID:25691832

Implicit anti-fat bias in physical educators: physical attributes, ideology and socialization.

PubMed

O'Brien, K S; Hunter, J A; Banks, M

2007-02-01

To investigate the implicit and explicit prejudice of physical education (PE) students before, and following extensive professional training, and to examine the relationship of anti-fat prejudice to relevant psychosocial predictors. Implicit and explicit anti-fat prejudice of year one and three PE students (cross-sectional sample) were assessed and compared to a similarly matched (age, body mass index (BMI), education) sample of psychology students. Three hundred and forty-four university students, 180 PE students, 164 psychology students (67% female, mean age 20 years, BMI: mean 23.18 kg/m(2)). Measures of implicit and explicit anti-fat prejudice were administered to PE and psychology students in either their second week, or near completion of their third year, of university study. Physical identity, body esteem and social dominance orientation (SDO) were assessed in order to establish their relationship with anti-fat bias. PE students displayed higher levels of implicit anti-fat bias than psychology students, and other health professionals. Additionally, year three PE students displayed higher levels of implicit anti-fat attitudes than year one PE students. The higher implicit anti-fat biases exhibited by year three PE students were associated with SDO, and lower body esteem. Physical educators, and particularly those more socialized in the PE environment, display strong negative prejudice toward obese individuals that is greater than that displayed by other groups. These prejudices appear to be supported by an over-investment in physical attributes, and ideological beliefs.

How implicit motives and everyday self-regulatory abilities shape cardiovascular risk in youth.

PubMed

Ewart, Craig K; Elder, Gavin J; Smyth, Joshua M

2012-06-01

Tested hypotheses from social action theory that (a) implicit and explicit measures of agonistic (social control) motives and transcendence (self-control) motives differentially predict cardiovascular risk; and (b) implicit motives interact with everyday self-regulation behaviors to magnify risk. Implicit/explicit agonistic/transcendence motives were assessed in a multi-ethnic sample of 64 high school students with the Social Competence Interview (SCI). Everyday self-regulation was assessed with teacher ratings of internalizing, externalizing, and self-control behaviors. Ambulatory blood pressure and daily activities were measured over 48 h. Study hypotheses were supported: implicit goals predicted blood pressure levels but explicit self-reported coping goals did not; self-regulation indices did not predict blood pressure directly but interacted with implicit agonistic/transcendence motives to identify individuals at greatest risk (all p ≤ 0.05). Assessment of implicit motives by SCI, and everyday self-regulation by teachers may improve identification of youth at risk for cardiovascular disease.

Identification as Gifted and Implicit Beliefs About Intelligence: An Examination of Potential Moderators

PubMed Central

Snyder, Kate E.; Barger, Michael M.; Wormington, Stephanie V.; Schwartz-Bloom, Rochelle; Linnenbrink-Garcia, Lisa

2015-01-01

The current study investigated whether the developmental timing of a student’s identification as gifted (i.e., when a student is first identified) was associated with later implicit beliefs about intelligence, and whether this relation is moderated by academic ability. A sample of 1,743 high-ability college students reported on whether and when they had been identified as gifted, academic ability (SAT scores), and implicit beliefs of intelligence. Timing of identification was unrelated to implicit beliefs; academic ability was the only significant predictor. Higher ability students who had been previously identified as gifted at any point in time reported implicit beliefs more toward entity beliefs than relatively lower ability students who had also been identified; however, this effect was quite small. Implicit beliefs did not vary by ability level for nonidentified students. These findings suggest that identification as gifted at any age modestly (but not necessarily meaningfully) relates to implicit beliefs for high-ability students. PMID:25729466

Health Care Providers’ Implicit and Explicit Attitudes Toward Lesbian Women and Gay Men

PubMed Central

Riskind, Rachel G.; Nosek, Brian A.

2015-01-01

Objectives. We examined providers’ implicit and explicit attitudes toward lesbian and gay people by provider gender, sexual identity, and race/ethnicity. Methods. We examined attitudes toward heterosexual people versus lesbian and gay people in Implicit Association Test takers: 2338 medical doctors, 5379 nurses, 8531 mental health providers, 2735 other treatment providers, and 214 110 nonproviders in the United States and internationally between May 2006 and December 2012. We characterized the sample with descriptive statistics and calculated Cohen d, a standardized effect size measure, with 95% confidence intervals. Results. Among heterosexual providers, implicit preferences always favored heterosexual people over lesbian and gay people. Implicit preferences for heterosexual women were weaker than implicit preferences for heterosexual men. Heterosexual nurses held the strongest implicit preference for heterosexual men over gay men (Cohen d = 1.30; 95% confidence interval = 1.28, 1.32 among female nurses; Cohen d = 1.38; 95% confidence interval = 1.32, 1.44 among male nurses). Among all groups, explicit preferences for heterosexual versus lesbian and gay people were weaker than implicit preferences. Conclusions. Implicit preferences for heterosexual people versus lesbian and gay people are pervasive among heterosexual health care providers. Future research should investigate how implicit sexual prejudice affects care. PMID:26180976

Using implicit association tests for the assessment of implicit personality self-concepts of extraversion and neuroticism in schizophrenia.

PubMed

Suslow, Thomas; Lindner, Christian; Kugel, Harald; Egloff, Boris; Schmukle, Stefan C

2014-08-30

There is evidence from research based on self-report personality measures that schizophrenia patients tend to be lower in extraversion and higher in neuroticism than healthy individuals. Self-report personality measures assess aspects of the explicit self-concept. The Implicit Association Test (IAT) has been developed to assess aspects of implicit cognition such as implicit attitudes and implicit personality traits. The present study was conducted to investigate the applicability and reliability of the IAT in schizophrenia patients and test whether they differ from healthy individuals on implicitly measured extraversion and neuroticism. The IAT and the NEO-FFI were administered as implicit and explicit measures of extraversion and neuroticism to 34 schizophrenia patients and 45 healthy subjects. For all IAT scores satisfactory to good reliabilities were observed in the patient sample. In both study groups, IAT scores were not related to NEO-FFI scores. Schizophrenia patients were lower in implicit and explicit extraversion and higher in implicit and explicit neuroticism than healthy individuals. Our data show that the IAT can be reliably applied to schizophrenia patients and suggest that they differ from healthy individuals not only in their conscious representation but also in their implicit representation of the self with regard to neuroticism and extraversion-related characteristics. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Metal–organic complexation in the marine environment

PubMed Central

Luther, George W; Rozan, Timothy F; Witter, Amy; Lewis, Brent

2001-01-01

We discuss the voltammetric methods that are used to assess metal–organic complexation in seawater. These consist of titration methods using anodic stripping voltammetry (ASV) and cathodic stripping voltammetry competitive ligand experiments (CSV-CLE). These approaches and a kinetic approach using CSV-CLE give similar information on the amount of excess ligand to metal in a sample and the conditional metal ligand stability constant for the excess ligand bound to the metal. CSV-CLE data using different ligands to measure Fe(III) organic complexes are similar. All these methods give conditional stability constants for which the side reaction coefficient for the metal can be corrected but not that for the ligand. Another approach, pseudovoltammetry, provides information on the actual metal–ligand complex(es) in a sample by doing ASV experiments where the deposition potential is varied more negatively in order to destroy the metal–ligand complex. This latter approach gives concentration information on each actual ligand bound to the metal as well as the thermodynamic stability constant of each complex in solution when compared to known metal–ligand complexes. In this case the side reaction coefficients for the metal and ligand are corrected. Thus, this method may not give identical information to the titration methods because the excess ligand in the sample may not be identical to some of the actual ligands binding the metal in the sample. PMID:16759421

Gender Stereotyping and Affective Attitudes Towards Science in Chinese Secondary School Students

NASA Astrophysics Data System (ADS)

Liu, Mingxin; Hu, Weiping; Jiannong, Shi; Adey, Philip

2010-02-01

This study explores explicit and implicit gender-science stereotypes and affective attitudes towards science in a sample of Chinese secondary school students. The results showed that (1) gender-science stereotyping was more and more apparent as the specialization of science subjects progresses through secondary school, becoming stronger from the 10th grade; girls were more inclined to stereotype than boys while this gender difference decreased with increasing grade; (2) girls tend to have an implicit science-unpleasant/humanities-pleasant association from the 8th grade, while boys showed a negative implicit attitude towards science up to the 11th grade. In self-report, girls preferred humanities to science, while boys preferred science to humanities; (3) implicit affective attitude was closely related to implicit stereotype. In particular, implicit affective attitude has a stronger predictive power on stereotype than the other way around, the result of which may have more significance for girls.

SAMPL5: 3D-RISM partition coefficient calculations with partial molar volume corrections and solute conformational sampling.

PubMed

Luchko, Tyler; Blinov, Nikolay; Limon, Garrett C; Joyce, Kevin P; Kovalenko, Andriy

2016-11-01

Implicit solvent methods for classical molecular modeling are frequently used to provide fast, physics-based hydration free energies of macromolecules. Less commonly considered is the transferability of these methods to other solvents. The Statistical Assessment of Modeling of Proteins and Ligands 5 (SAMPL5) distribution coefficient dataset and the accompanying explicit solvent partition coefficient reference calculations provide a direct test of solvent model transferability. Here we use the 3D reference interaction site model (3D-RISM) statistical-mechanical solvation theory, with a well tested water model and a new united atom cyclohexane model, to calculate partition coefficients for the SAMPL5 dataset. The cyclohexane model performed well in training and testing ([Formula: see text] for amino acid neutral side chain analogues) but only if a parameterized solvation free energy correction was used. In contrast, the same protocol, using single solute conformations, performed poorly on the SAMPL5 dataset, obtaining [Formula: see text] compared to the reference partition coefficients, likely due to the much larger solute sizes. Including solute conformational sampling through molecular dynamics coupled with 3D-RISM (MD/3D-RISM) improved agreement with the reference calculation to [Formula: see text]. Since our initial calculations only considered partition coefficients and not distribution coefficients, solute sampling provided little benefit comparing against experiment, where ionized and tautomer states are more important. Applying a simple [Formula: see text] correction improved agreement with experiment from [Formula: see text] to [Formula: see text], despite a small number of outliers. Better agreement is possible by accounting for tautomers and improving the ionization correction.

SAMPL5: 3D-RISM partition coefficient calculations with partial molar volume corrections and solute conformational sampling

NASA Astrophysics Data System (ADS)

Luchko, Tyler; Blinov, Nikolay; Limon, Garrett C.; Joyce, Kevin P.; Kovalenko, Andriy

2016-11-01

Implicit solvent methods for classical molecular modeling are frequently used to provide fast, physics-based hydration free energies of macromolecules. Less commonly considered is the transferability of these methods to other solvents. The Statistical Assessment of Modeling of Proteins and Ligands 5 (SAMPL5) distribution coefficient dataset and the accompanying explicit solvent partition coefficient reference calculations provide a direct test of solvent model transferability. Here we use the 3D reference interaction site model (3D-RISM) statistical-mechanical solvation theory, with a well tested water model and a new united atom cyclohexane model, to calculate partition coefficients for the SAMPL5 dataset. The cyclohexane model performed well in training and testing (R=0.98 for amino acid neutral side chain analogues) but only if a parameterized solvation free energy correction was used. In contrast, the same protocol, using single solute conformations, performed poorly on the SAMPL5 dataset, obtaining R=0.73 compared to the reference partition coefficients, likely due to the much larger solute sizes. Including solute conformational sampling through molecular dynamics coupled with 3D-RISM (MD/3D-RISM) improved agreement with the reference calculation to R=0.93. Since our initial calculations only considered partition coefficients and not distribution coefficients, solute sampling provided little benefit comparing against experiment, where ionized and tautomer states are more important. Applying a simple pK_{ {a}} correction improved agreement with experiment from R=0.54 to R=0.66, despite a small number of outliers. Better agreement is possible by accounting for tautomers and improving the ionization correction.

Refinement of NMR structures using implicit solvent and advanced sampling techniques.

PubMed

Chen, Jianhan; Im, Wonpil; Brooks, Charles L

2004-12-15

NMR biomolecular structure calculations exploit simulated annealing methods for conformational sampling and require a relatively high level of redundancy in the experimental restraints to determine quality three-dimensional structures. Recent advances in generalized Born (GB) implicit solvent models should make it possible to combine information from both experimental measurements and accurate empirical force fields to improve the quality of NMR-derived structures. In this paper, we study the influence of implicit solvent on the refinement of protein NMR structures and identify an optimal protocol of utilizing these improved force fields. To do so, we carry out structure refinement experiments for model proteins with published NMR structures using full NMR restraints and subsets of them. We also investigate the application of advanced sampling techniques to NMR structure refinement. Similar to the observations of Xia et al. (J.Biomol. NMR 2002, 22, 317-331), we find that the impact of implicit solvent is rather small when there is a sufficient number of experimental restraints (such as in the final stage of NMR structure determination), whether implicit solvent is used throughout the calculation or only in the final refinement step. The application of advanced sampling techniques also seems to have minimal impact in this case. However, when the experimental data are limited, we demonstrate that refinement with implicit solvent can substantially improve the quality of the structures. In particular, when combined with an advanced sampling technique, the replica exchange (REX) method, near-native structures can be rapidly moved toward the native basin. The REX method provides both enhanced sampling and automatic selection of the most native-like (lowest energy) structures. An optimal protocol based on our studies first generates an ensemble of initial structures that maximally satisfy the available experimental data with conventional NMR software using a simplified force field and then refines these structures with implicit solvent using the REX method. We systematically examine the reliability and efficacy of this protocol using four proteins of various sizes ranging from the 56-residue B1 domain of Streptococcal protein G to the 370-residue Maltose-binding protein. Significant improvement in the structures was observed in all cases when refinement was based on low-redundancy restraint data. The proposed protocol is anticipated to be particularly useful in early stages of NMR structure determination where a reliable estimate of the native fold from limited data can significantly expedite the overall process. This refinement procedure is also expected to be useful when redundant experimental data are not readily available, such as for large multidomain biomolecules and in solid-state NMR structure determination.

Binding Modes of Ligands Using Enhanced Sampling (BLUES): Rapid Decorrelation of Ligand Binding Modes via Nonequilibrium Candidate Monte Carlo.

PubMed

Gill, Samuel C; Lim, Nathan M; Grinaway, Patrick B; Rustenburg, Ariën S; Fass, Josh; Ross, Gregory A; Chodera, John D; Mobley, David L

2018-05-31

Accurately predicting protein-ligand binding affinities and binding modes is a major goal in computational chemistry, but even the prediction of ligand binding modes in proteins poses major challenges. Here, we focus on solving the binding mode prediction problem for rigid fragments. That is, we focus on computing the dominant placement, conformation, and orientations of a relatively rigid, fragment-like ligand in a receptor, and the populations of the multiple binding modes which may be relevant. This problem is important in its own right, but is even more timely given the recent success of alchemical free energy calculations. Alchemical calculations are increasingly used to predict binding free energies of ligands to receptors. However, the accuracy of these calculations is dependent on proper sampling of the relevant ligand binding modes. Unfortunately, ligand binding modes may often be uncertain, hard to predict, and/or slow to interconvert on simulation time scales, so proper sampling with current techniques can require prohibitively long simulations. We need new methods which dramatically improve sampling of ligand binding modes. Here, we develop and apply a nonequilibrium candidate Monte Carlo (NCMC) method to improve sampling of ligand binding modes. In this technique, the ligand is rotated and subsequently allowed to relax in its new position through alchemical perturbation before accepting or rejecting the rotation and relaxation as a nonequilibrium Monte Carlo move. When applied to a T4 lysozyme model binding system, this NCMC method shows over 2 orders of magnitude improvement in binding mode sampling efficiency compared to a brute force molecular dynamics simulation. This is a first step toward applying this methodology to pharmaceutically relevant binding of fragments and, eventually, drug-like molecules. We are making this approach available via our new Binding modes of ligands using enhanced sampling (BLUES) package which is freely available on GitHub.

Molecular dynamics simulations of biological membranes and membrane proteins using enhanced conformational sampling algorithms☆

PubMed Central

Mori, Takaharu; Miyashita, Naoyuki; Im, Wonpil; Feig, Michael; Sugita, Yuji

2016-01-01

This paper reviews various enhanced conformational sampling methods and explicit/implicit solvent/membrane models, as well as their recent applications to the exploration of the structure and dynamics of membranes and membrane proteins. Molecular dynamics simulations have become an essential tool to investigate biological problems, and their success relies on proper molecular models together with efficient conformational sampling methods. The implicit representation of solvent/membrane environments is reasonable approximation to the explicit all-atom models, considering the balance between computational cost and simulation accuracy. Implicit models can be easily combined with replica-exchange molecular dynamics methods to explore a wider conformational space of a protein. Other molecular models and enhanced conformational sampling methods are also briefly discussed. As application examples, we introduce recent simulation studies of glycophorin A, phospholamban, amyloid precursor protein, and mixed lipid bilayers and discuss the accuracy and efficiency of each simulation model and method. This article is part of a Special Issue entitled: Membrane Proteins. Guest Editors: J.C. Gumbart and Sergei Noskov. PMID:26766517

Decisions among the Undecided: Implicit Attitudes Predict Future Voting Behavior of Undecided Voters

PubMed Central

Lundberg, Kristjen B.; Payne, B. Keith

2014-01-01

Implicit attitudes have been suggested as a key to unlock the hidden preferences of undecided voters. Past research, however, offered mixed support for this hypothesis. The present research used a large nationally representative sample and a longitudinal design to examine the predictive utility of implicit and explicit attitude measures in the 2008 U.S. presidential election. In our analyses, explicit attitudes toward candidates predicted voting better for decided than undecided voters, but implicit candidate attitudes were predictive of voting for both decided and undecided voters. Extending our examination to implicit and explicit racial attitudes, we found the same pattern. Taken together, these results provide convergent evidence that implicit attitudes predict voting about as well for undecided as for decided voters. We also assessed a novel explanation for these effects by evaluating whether implicit attitudes may predict the choices of undecided voters, in part, because they are neglected when people introspect about their confidence. Consistent with this idea, we found that the extremity of explicit but not implicit attitudes was associated with greater confidence. These analyses shed new light on the utility of implicit measures in predicting future behavior among individuals who feel undecided. Considering the prior studies together with this new evidence, the data seem to be consistent that implicit attitudes may be successful in predicting the behavior of undecided voters. PMID:24489666

Characterizing Implicit Mental Health Associations across Clinical Domains

PubMed Central

Werntz, Alexandra J.; Steinman, Shari A.; Glenn, Jeffrey J.; Nock, Matthew K.; Teachman, Bethany A.

2016-01-01

Background and objectives Implicit associations are relatively uncontrollable associations between concepts in memory. The current investigation focuses on implicit associations in four mental health domains (alcohol use, anxiety, depression, and eating disorders) and how these implicit associations: a) relate to explicit associations and b) self-reported clinical symptoms within the same domains, and c) vary based on demographic characteristics (age, gender, race, ethnicity, and education). Methods Participants (volunteers over age 18 to a research website) completed implicit association (Implicit Association Tests), explicit association (self+psychopathology or attitudes toward food, using semantic differential items), and symptom measures at the Project Implicit Mental Health website tied to: alcohol use (N=12,387), anxiety (N=21,304), depression (N=24,126), or eating disorders (N=10,115). Results Within each domain, implicit associations showed small to moderate associations with explicit associations and symptoms, and predicted self-reported symptoms beyond explicit associations. In general, implicit association strength varied little by race and ethnicity, but showed small ties to age, gender, and education. Limitations This research was conducted on a public research and education website, where participants could take more than one of the studies. Conclusions Among a large and diverse sample, implicit associations in the four domains are congruent with explicit associations and self-reported symptoms, and also add to our prediction of self-reported symptoms over and above explicit associations, pointing to the potential future clinical utility and validity of using implicit association measures with diverse populations. PMID:26962979

Characterizing implicit mental health associations across clinical domains.

PubMed

Werntz, Alexandra J; Steinman, Shari A; Glenn, Jeffrey J; Nock, Matthew K; Teachman, Bethany A

2016-09-01

Implicit associations are relatively uncontrollable associations between concepts in memory. The current investigation focuses on implicit associations in four mental health domains (alcohol use, anxiety, depression, and eating disorders) and how these implicit associations: a) relate to explicit associations and b) self-reported clinical symptoms within the same domains, and c) vary based on demographic characteristics (age, gender, race, ethnicity, and education). Participants (volunteers over age 18 to a research website) completed implicit association (Implicit Association Tests), explicit association (self + psychopathology or attitudes toward food, using semantic differential items), and symptom measures at the Project Implicit Mental Health website tied to: alcohol use (N = 12,387), anxiety (N = 21,304), depression (N = 24,126), or eating disorders (N = 10,115). Within each domain, implicit associations showed small to moderate associations with explicit associations and symptoms, and predicted self-reported symptoms beyond explicit associations. In general, implicit association strength varied little by race and ethnicity, but showed small ties to age, gender, and education. This research was conducted on a public research and education website, where participants could take more than one of the studies. Among a large and diverse sample, implicit associations in the four domains are congruent with explicit associations and self-reported symptoms, and also add to our prediction of self-reported symptoms over and above explicit associations, pointing to the potential future clinical utility and validity of using implicit association measures with diverse populations. Copyright © 2016 Elsevier Ltd. All rights reserved.

Investigating the predictive validity of implicit and explicit measures of motivation on condom use, physical activity and healthy eating.

PubMed

Keatley, David; Clarke, David D; Hagger, Martin S

2012-01-01

The literature on health-related behaviours and motivation is replete with research involving explicit processes and their relations with intentions and behaviour. Recently, interest has been focused on the impact of implicit processes and measures on health-related behaviours. Dual-systems models have been proposed to provide a framework for understanding the effects of explicit or deliberative and implicit or impulsive processes on health behaviours. Informed by a dual-systems approach and self-determination theory, the aim of this study was to test the effects of implicit and explicit motivation on three health-related behaviours in a sample of undergraduate students (N = 162). Implicit motives were hypothesised to predict behaviour independent of intentions while explicit motives would be mediated by intentions. Regression analyses indicated that implicit motivation predicted physical activity behaviour only. Across all behaviours, intention mediated the effects of explicit motivational variables from self-determination theory. This study provides limited support for dual-systems models and the role of implicit motivation in the prediction of health-related behaviour. Suggestions for future research into the role of implicit processes in motivation are outlined.

Implicit alcohol attitudes predict drinking behaviour over and above intentions and willingness in young adults but willingness is more important in adolescents: Implications for the Prototype Willingness Model.

PubMed

Davies, Emma L; Paltoglou, Aspasia E; Foxcroft, David R

2017-05-01

Dual process models, such as the Prototype Willingness Model (PWM), propose to account for both intentional and reactive drinking behaviour. Current methods of measuring constructs in the PWM rely on self-report, thus require a level of conscious deliberation. Implicit measures of attitudes may overcome this limitation and contribute to our understanding of how prototypes and willingness influence alcohol consumption in young people. This study aimed to explore whether implicit alcohol attitudes were related to PWM constructs and whether they would add to the prediction of risky drinking. The study involved a cross-sectional design. The sample included 501 participants from the United Kingdom (M age 18.92; range 11-51; 63% female); 230 school pupils and 271 university students. Participants completed explicit measures of alcohol prototype perceptions, willingness, drunkenness, harms, and intentions. They also completed an implicit measure of alcohol attitudes, using the Implicit Association Test. Implicit alcohol attitudes were only weakly related to the explicit measures. When looking at the whole sample, implicit alcohol attitudes did not add to the prediction of willingness over and above prototype perceptions. However, for university students implicit attitudes added to the prediction of behaviour, over and above intentions and willingness. For school pupils, willingness was a stronger predictor of behaviour than intentions or implicit attitudes. Adding implicit measures to the PWM may contribute to our understanding of the development of alcohol behaviours in young people. Further research could explore how implicit attitudes develop alongside the shift from reactive to planned behaviour. Statement of contribution What is already known on this subject? Young people's drinking tends to occur in social situations and is driven in part by social reactions within these contexts. The Prototype Willingness Model (PWM) attempts to explain such reactive behaviour as the result of social comparison to risk prototypes, which influence willingness to drink, and subsequent behaviour. Evidence also suggests that risky drinking in young people may be influenced by implicit attitudes towards alcohol, which develop with repeated exposure to alcohol over time. One criticism of the PWM is that prototypes and willingness are usually measured using explicit measures which may not adequately capture young people's spontaneous evaluations of prototypes, or their propensity to act without forethought in a social context. What does this study add? This study is novel in exploring the addition of implicit alcohol attitudes to the social reaction pathway in the model in order to understand more about these reactive constructs. Implicit alcohol attitudes added to the prediction of behaviour, over and above intentions and willingness for university students. For school pupils, willingness was a stronger predictor of behaviour than intentions or implicit attitudes. Findings suggest that adding implicit alcohol attitudes into the PWM might be able to explain the shift from reactive to intentional drinking behaviours with age and experience. © 2016 The British Psychological Society.

Enhanced Ligand Sampling for Relative Protein–Ligand Binding Free Energy Calculations

PubMed Central

2016-01-01

Free energy calculations are used to study how strongly potential drug molecules interact with their target receptors. The accuracy of these calculations depends on the accuracy of the molecular dynamics (MD) force field as well as proper sampling of the major conformations of each molecule. However, proper sampling of ligand conformations can be difficult when there are large barriers separating the major ligand conformations. An example of this is for ligands with an asymmetrically substituted phenyl ring, where the presence of protein loops hinders the proper sampling of the different ring conformations. These ring conformations become more difficult to sample when the size of the functional groups attached to the ring increases. The Adaptive Integration Method (AIM) has been developed, which adaptively changes the alchemical coupling parameter λ during the MD simulation so that conformations sampled at one λ can aid sampling at the other λ values. The Accelerated Adaptive Integration Method (AcclAIM) builds on AIM by lowering potential barriers for specific degrees of freedom at intermediate λ values. However, these methods may not work when there are very large barriers separating the major ligand conformations. In this work, we describe a modification to AIM that improves sampling of the different ring conformations, even when there is a very large barrier between them. This method combines AIM with conformational Monte Carlo sampling, giving improved convergence of ring populations and the resulting free energy. This method, called AIM/MC, is applied to study the relative binding free energy for a pair of ligands that bind to thrombin and a different pair of ligands that bind to aspartyl protease β-APP cleaving enzyme 1 (BACE1). These protein–ligand binding free energy calculations illustrate the improvements in conformational sampling and the convergence of the free energy compared to both AIM and AcclAIM. PMID:25906170

Explicit treatment of active-site waters enhances quantum mechanical/implicit solvent scoring: Inhibition of CDK2 by new pyrazolo[1,5-a]pyrimidines.

PubMed

Hylsová, Michaela; Carbain, Benoit; Fanfrlík, Jindřich; Musilová, Lenka; Haldar, Susanta; Köprülüoğlu, Cemal; Ajani, Haresh; Brahmkshatriya, Pathik S; Jorda, Radek; Kryštof, Vladimír; Hobza, Pavel; Echalier, Aude; Paruch, Kamil; Lepšík, Martin

2017-01-27

We present comprehensive testing of solvent representation in quantum mechanics (QM)-based scoring of protein-ligand affinities. To this aim, we prepared 21 new inhibitors of cyclin-dependent kinase 2 (CDK2) with the pyrazolo[1,5-a]pyrimidine core, whose activities spanned three orders of magnitude. The crystal structure of a potent inhibitor bound to the active CDK2/cyclin A complex revealed that the biphenyl substituent at position 5 of the pyrazolo[1,5-a]pyrimidine scaffold was located in a previously unexplored pocket and that six water molecules resided in the active site. Using molecular dynamics, protein-ligand interactions and active-site water H-bond networks as well as thermodynamics were probed. Thereafter, all the inhibitors were scored by the QM approach utilizing the COSMO implicit solvent model. Such a standard treatment failed to produce a correlation with the experiment (R 2  = 0.49). However, the addition of the active-site waters resulted in significant improvement (R 2  = 0.68). The activities of the compounds could thus be interpreted by taking into account their specific noncovalent interactions with CDK2 and the active-site waters. In summary, using a combination of several experimental and theoretical approaches we demonstrate that the inclusion of explicit solvent effects enhance QM/COSMO scoring to produce a reliable structure-activity relationship with physical insights. More generally, this approach is envisioned to contribute to increased accuracy of the computational design of novel inhibitors. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Measuring Gifted Adolescents' Implicit Theories of Creativity

ERIC Educational Resources Information Center

Wickes, Katherine N. Saunders; Ward, Thomas B.

2006-01-01

This paper examines the structure of implicit theories of creativity in a sample of gifted adolescents and describes the development and use of the Creative Self Checklist and the Creative Individual Checklist, adjective checklists designed to assess endorsement of creativity-related personality and behavioral attributes. Findings indicate that…

Are implicit motives revealed in mere words? Testing the marker-word hypothesis with computer-based text analysis

PubMed Central

Schultheiss, Oliver C.

2013-01-01

Traditionally, implicit motives (i.e., non-conscious preferences for specific classes of incentives) are assessed through semantic coding of imaginative stories. The present research tested the marker-word hypothesis, which states that implicit motives are reflected in the frequencies of specific words. Using Linguistic Inquiry and Word Count (LIWC; Pennebaker et al., 2001), Study 1 identified word categories that converged with a content-coding measure of the implicit motives for power, achievement, and affiliation in picture stories collected in German and US student samples, showed discriminant validity with self-reported motives, and predicted well-validated criteria of implicit motives (gender difference for the affiliation motive; in interaction with personal-goal progress: emotional well-being). Study 2 demonstrated LIWC-based motive scores' causal validity by documenting their sensitivity to motive arousal. PMID:24137149

Analysis of macromolecules, ligands and macromolecule-ligand complexes

DOEpatents

Von Dreele, Robert B [Los Alamos, NM

2008-12-23

A method for determining atomic level structures of macromolecule-ligand complexes through high-resolution powder diffraction analysis and a method for providing suitable microcrystalline powder for diffraction analysis are provided. In one embodiment, powder diffraction data is collected from samples of polycrystalline macromolecule and macromolecule-ligand complex and the refined structure of the macromolecule is used as an approximate model for a combined Rietveld and stereochemical restraint refinement of the macromolecule-ligand complex. A difference Fourier map is calculated and the ligand position and points of interaction between the atoms of the macromolecule and the atoms of the ligand can be deduced and visualized. A suitable polycrystalline sample of macromolecule-ligand complex can be produced by physically agitating a mixture of lyophilized macromolecule, ligand and a solvent.

DFT Virtual Screening Identifies Rhodium–Amidinate Complexes As Potential Homogeneous Catalysts for Methane-to-Methanol Oxidation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fu, Ross; Nielsen, Robert J.; Goddard, William A.

2014-11-11

In the search for new organometallic catalysts for low-temperature selective conversion of CH4 to CH3OH, we apply quantum mechanical virtual screening to select the optimum combination of ligand and solvent on rhodium to achieve low barriers for CH4 activation and functionalization to recommend for experimental validation. Here, we considered Rh because its lower electronegativity compared with Pt and Pd may allow it to avoid poisoning by coordinating media. We report quantum mechanical predictions (including implicit and explicit solvation) of the mechanisms for RhIII(NN) and RhIII(NNF) complexes [where (NN) = bis(N-phenyl)benzylamidinate and (NNF) = bis(N-pentafluorophenyl)pentafluorobenzylamidinate] to catalytically activate and functionalize methanemore » using trifluoroacetic acid (TFAH) or water as a solvent. In particular, we designed the (NNF) ligand as a more electrophilic analogue to the (NN) ligand, and our results predict the lowest transition state barrier (ΔG‡ = 27.6 kcal/mol) for methane activation in TFAH from a pool of four different classes of ligands. To close the catalytic cycle, the functionalization of methylrhodium intermediates was also investigated, involving carbon–oxygen bond formation via SN2 attack by solvent, or SR2 attack by a vanadium oxo. Activation barriers for the functionalization of methylrhodium intermediates via nucleophilic attack are lower when the solvent is water, but CH4 activation barriers are higher. In addition, we have found a correlation between CH4 activation barriers and rhodium–methyl bond energies that allow us to predict the activation transition state energies for future ligands, as well.« less

Investigation of MM-PBSA rescoring of docking poses.

PubMed

Thompson, David C; Humblet, Christine; Joseph-McCarthy, Diane

2008-05-01

Target-based virtual screening is increasingly used to generate leads for targets for which high quality three-dimensional (3D) structures are available. To allow large molecular databases to be screened rapidly, a tiered scoring scheme is often employed whereby a simple scoring function is used as a fast filter of the entire database and a more rigorous and time-consuming scoring function is used to rescore the top hits to produce the final list of ranked compounds. Molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) approaches are currently thought to be quite effective at incorporating implicit solvation into the estimation of ligand binding free energies. In this paper, the ability of a high-throughput MM-PBSA rescoring function to discriminate between correct and incorrect docking poses is investigated in detail. Various initial scoring functions are used to generate docked poses for a subset of the CCDC/Astex test set and to dock one set of actives/inactives from the DUD data set. The effectiveness of each of these initial scoring functions is discussed. Overall, the ability of the MM-PBSA rescoring function to (i) regenerate the set of X-ray complexes when docking the bound conformation of the ligand, (ii) regenerate the X-ray complexes when docking conformationally expanded databases for each ligand which include "conformation decoys" of the ligand, and (iii) enrich known actives in a virtual screen for the mineralocorticoid receptor in the presence of "ligand decoys" is assessed. While a pharmacophore-based molecular docking approach, PhDock, is used to carry out the docking, the results are expected to be general to use with any docking method.

Explicit versus Implicit Social Cognition Testing in Autism Spectrum Disorder

ERIC Educational Resources Information Center

Callenmark, Björn; Kjellin, Lars; Rönnqvist, Louise; Bölte, Sven

2014-01-01

Although autism spectrum disorder is defined by reciprocal social-communication impairments, several studies have found no evidence for altered social cognition test performance. This study examined explicit (i.e. prompted) and implicit (i.e. spontaneous) variants of social cognition testing in autism spectrum disorder. A sample of 19 adolescents…

CHARMM: The Biomolecular Simulation Program

PubMed Central

Brooks, B.R.; Brooks, C.L.; MacKerell, A.D.; Nilsson, L.; Petrella, R.J.; Roux, B.; Won, Y.; Archontis, G.; Bartels, C.; Boresch, S.; Caflisch, A.; Caves, L.; Cui, Q.; Dinner, A.R.; Feig, M.; Fischer, S.; Gao, J.; Hodoscek, M.; Im, W.; Kuczera, K.; Lazaridis, T.; Ma, J.; Ovchinnikov, V.; Paci, E.; Pastor, R.W.; Post, C.B.; Pu, J.Z.; Schaefer, M.; Tidor, B.; Venable, R. M.; Woodcock, H. L.; Wu, X.; Yang, W.; York, D.M.; Karplus, M.

2009-01-01

CHARMM (Chemistry at HARvard Molecular Mechanics) is a highly versatile and widely used molecular simulation program. It has been developed over the last three decades with a primary focus on molecules of biological interest, including proteins, peptides, lipids, nucleic acids, carbohydrates and small molecule ligands, as they occur in solution, crystals, and membrane environments. For the study of such systems, the program provides a large suite of computational tools that include numerous conformational and path sampling methods, free energy estimators, molecular minimization, dynamics, and analysis techniques, and model-building capabilities. In addition, the CHARMM program is applicable to problems involving a much broader class of many-particle systems. Calculations with CHARMM can be performed using a number of different energy functions and models, from mixed quantum mechanical-molecular mechanical force fields, to all-atom classical potential energy functions with explicit solvent and various boundary conditions, to implicit solvent and membrane models. The program has been ported to numerous platforms in both serial and parallel architectures. This paper provides an overview of the program as it exists today with an emphasis on developments since the publication of the original CHARMM paper in 1983. PMID:19444816

Can a continuum solvent model reproduce the free energy landscape of a -hairpin folding in water?

NASA Astrophysics Data System (ADS)

Zhou, Ruhong; Berne, Bruce J.

2002-10-01

The folding free energy landscape of the C-terminal -hairpin of protein G is explored using the surface-generalized Born (SGB) implicit solvent model, and the results are compared with the landscape from an earlier study with explicit solvent model. The OPLSAA force field is used for the -hairpin in both implicit and explicit solvent simulations, and the conformational space sampling is carried out with a highly parallel replica-exchange method. Surprisingly, we find from exhaustive conformation space sampling that the free energy landscape from the implicit solvent model is quite different from that of the explicit solvent model. In the implicit solvent model some nonnative states are heavily overweighted, and more importantly, the lowest free energy state is no longer the native -strand structure. An overly strong salt-bridge effect between charged residues (E42, D46, D47, E56, and K50) is found to be responsible for this behavior in the implicit solvent model. Despite this, we find that the OPLSAA/SGB energies of all the nonnative structures are higher than that of the native structure; thus the OPLSAA/SGB energy is still a good scoring function for structure prediction for this -hairpin. Furthermore, the -hairpin population at 282 K is found to be less than 40% from the implicit solvent model, which is much smaller than the 72% from the explicit solvent model and 80% from experiment. On the other hand, both implicit and explicit solvent simulations with the OPLSAA force field exhibit no meaningful helical content during the folding process, which is in contrast to some very recent studies using other force fields.

Can a continuum solvent model reproduce the free energy landscape of a β-hairpin folding in water?

PubMed Central

Zhou, Ruhong; Berne, Bruce J.

2002-01-01

The folding free energy landscape of the C-terminal β-hairpin of protein G is explored using the surface-generalized Born (SGB) implicit solvent model, and the results are compared with the landscape from an earlier study with explicit solvent model. The OPLSAA force field is used for the β-hairpin in both implicit and explicit solvent simulations, and the conformational space sampling is carried out with a highly parallel replica-exchange method. Surprisingly, we find from exhaustive conformation space sampling that the free energy landscape from the implicit solvent model is quite different from that of the explicit solvent model. In the implicit solvent model some nonnative states are heavily overweighted, and more importantly, the lowest free energy state is no longer the native β-strand structure. An overly strong salt-bridge effect between charged residues (E42, D46, D47, E56, and K50) is found to be responsible for this behavior in the implicit solvent model. Despite this, we find that the OPLSAA/SGB energies of all the nonnative structures are higher than that of the native structure; thus the OPLSAA/SGB energy is still a good scoring function for structure prediction for this β-hairpin. Furthermore, the β-hairpin population at 282 K is found to be less than 40% from the implicit solvent model, which is much smaller than the 72% from the explicit solvent model and ≈80% from experiment. On the other hand, both implicit and explicit solvent simulations with the OPLSAA force field exhibit no meaningful helical content during the folding process, which is in contrast to some very recent studies using other force fields. PMID:12242327

Can a continuum solvent model reproduce the free energy landscape of a beta -hairpin folding in water?

PubMed

Zhou, Ruhong; Berne, Bruce J

2002-10-01

The folding free energy landscape of the C-terminal beta-hairpin of protein G is explored using the surface-generalized Born (SGB) implicit solvent model, and the results are compared with the landscape from an earlier study with explicit solvent model. The OPLSAA force field is used for the beta-hairpin in both implicit and explicit solvent simulations, and the conformational space sampling is carried out with a highly parallel replica-exchange method. Surprisingly, we find from exhaustive conformation space sampling that the free energy landscape from the implicit solvent model is quite different from that of the explicit solvent model. In the implicit solvent model some nonnative states are heavily overweighted, and more importantly, the lowest free energy state is no longer the native beta-strand structure. An overly strong salt-bridge effect between charged residues (E42, D46, D47, E56, and K50) is found to be responsible for this behavior in the implicit solvent model. Despite this, we find that the OPLSAA/SGB energies of all the nonnative structures are higher than that of the native structure; thus the OPLSAA/SGB energy is still a good scoring function for structure prediction for this beta-hairpin. Furthermore, the beta-hairpin population at 282 K is found to be less than 40% from the implicit solvent model, which is much smaller than the 72% from the explicit solvent model and approximately equal 80% from experiment. On the other hand, both implicit and explicit solvent simulations with the OPLSAA force field exhibit no meaningful helical content during the folding process, which is in contrast to some very recent studies using other force fields.

Habit Doesn’t Make the Predictions Stronger: Implicit Alcohol Associations and Habitualness Predict Drinking Uniquely

PubMed Central

Lindgren, Kristen P.; Neighbors, Clayton; Teachman, Bethany A.; Gasser, Melissa L.; Kaysen, Debra; Norris, Jeanette; Wiers, Reinout W.

2015-01-01

Introduction As research on implicit (in the sense of fast/reflexive/impulsive) alcohol associations and alcohol advances, there is increasing emphasis on understanding the circumstances under which implicit alcohol associations predict drinking. In this study, we investigated habitualness of drinking (i.e., the extent to which drinking is automatic or occurs without thinking) as a moderator of the relations between several measures of implicit alcohol associations and key drinking outcomes. Method A sample of 506 participants (57% female) completed web-based measures of implicit alcohol associations (drinking identity, alcohol approach, and alcohol excitement), along with indicators of habitualness, and typical alcohol consumption, alcohol problems, and risk of alcohol use disorders. Results As expected, implicit alcohol associations, especially drinking identity, were positively associated with, and predicted unique variance in, drinking outcomes. Further, habitualness emerged as a consistent, positive predictor of drinking outcomes. Contrary to expectations, habitualness rarely moderated the relation between implicit alcohol associations and drinking outcomes. Conclusions Although moderation was rarely observed, findings indicated that even mild levels of habitualness are risky. Findings also continue to support implicit alcohol associations, particularly drinking identity, as a risk factor for hazardous drinking. Collectively, this suggests the importance of targeting both in prevention and intervention efforts. PMID:25665917

Moderators of the Relationship between Implicit and Explicit Evaluation

PubMed Central

Nosek, Brian A.

2005-01-01

Automatic and controlled modes of evaluation sometimes provide conflicting reports of the quality of social objects. This paper presents evidence for four moderators of the relationship between automatic (implicit) and controlled (explicit) evaluations. Implicit and explicit preferences were measured for a variety of object pairs using a large sample. The average correlation was r = .36, and 52 of the 57 object pairs showed a significant positive correlation. Results of multilevel modeling analyses suggested that: (a) implicit and explicit preferences are related, (b) the relationship varies as a function of the objects assessed, and (c) at least four variables moderate the relationship – self-presentation, evaluative strength, dimensionality, and distinctiveness. The variables moderated implicit-explicit correspondence across individuals and accounted for much of the observed variation across content domains. The resulting model of the relationship between automatic and controlled evaluative processes is grounded in personal experience with the targets of evaluation. PMID:16316292

Young Adults' Implicit and Explicit Attitudes towards the Sexuality of Older Adults.

PubMed

Thompson, Ashley E; O'Sullivan, Lucia F; Byers, E Sandra; Shaughnessy, Krystelle

2014-09-01

Sexual interest and capacity can extend far into later life and result in many positive health outcomes. Yet there is little support for sexual expression in later life, particularly among young adults. This study assessed and compared young adults' explicit and implicit attitudes towards older adult sexuality. A sample of 120 participants (18-24 years; 58% female) completed a self-report (explicit) measure and a series of Implicit Association Tests capturing attitudes towards sexuality among older adults. Despite reporting positive explicit attitudes, young people revealed an implicit bias against the sexual lives of older adults. In particular, young adults demonstrated implicit biases favouring general, as compared to sexual, activities and young adults as compared to older adults. Moreover, the bias favouring general activities was amplified with regard to older adults as compared to younger adults. Our findings challenge the validity of research relying on self-reports of attitudes about older adult sexuality.

Molecular dynamics simulations of biological membranes and membrane proteins using enhanced conformational sampling algorithms.

PubMed

Mori, Takaharu; Miyashita, Naoyuki; Im, Wonpil; Feig, Michael; Sugita, Yuji

2016-07-01

This paper reviews various enhanced conformational sampling methods and explicit/implicit solvent/membrane models, as well as their recent applications to the exploration of the structure and dynamics of membranes and membrane proteins. Molecular dynamics simulations have become an essential tool to investigate biological problems, and their success relies on proper molecular models together with efficient conformational sampling methods. The implicit representation of solvent/membrane environments is reasonable approximation to the explicit all-atom models, considering the balance between computational cost and simulation accuracy. Implicit models can be easily combined with replica-exchange molecular dynamics methods to explore a wider conformational space of a protein. Other molecular models and enhanced conformational sampling methods are also briefly discussed. As application examples, we introduce recent simulation studies of glycophorin A, phospholamban, amyloid precursor protein, and mixed lipid bilayers and discuss the accuracy and efficiency of each simulation model and method. This article is part of a Special Issue entitled: Membrane Proteins edited by J.C. Gumbart and Sergei Noskov. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Teachers' Implicit Theories of Intelligence: Influences from Different Disciplines and Scientific Theories

ERIC Educational Resources Information Center

Jonsson, Anna-Carin; Beach, Dennis; Korp, Helena; Erlandson, Peter

2012-01-01

A sample of 226 Swedish high school teachers from various knowledge domains completed self-report measures of intelligence regarding implicit theories and scientific theories of intelligence. A mixed ANOVA showed that teachers from language, social science and practical disciplines had a significant preference for an incremental theory of…

Incidental Learning of Melodic Structure of North Indian Music

ERIC Educational Resources Information Center

Rohrmeier, Martin; Widdess, Richard

2017-01-01

Musical knowledge is largely implicit. It is acquired without awareness of its complex rules, through interaction with a large number of samples during musical enculturation. Whereas several studies explored implicit learning of mostly abstract and less ecologically valid features of Western music, very little work has been done with respect to…

Implicit Social Cognitions Predict Sex Differences in Math Engagement and Achievement

ERIC Educational Resources Information Center

Nosek, Brian A.; Smyth, Frederick L.

2011-01-01

Gender stereotypes about math and science do not need to be endorsed, or even available to conscious introspection, to contribute to the sex gap in engagement and achievement in science, technology, engineering, and mathematics (STEM). The authors examined implicit math attitudes and stereotypes among a heterogeneous sample of 5,139 participants.…

IMPLICIT DUAL CONTROL BASED ON PARTICLE FILTERING AND FORWARD DYNAMIC PROGRAMMING.

PubMed

Bayard, David S; Schumitzky, Alan

2010-03-01

This paper develops a sampling-based approach to implicit dual control. Implicit dual control methods synthesize stochastic control policies by systematically approximating the stochastic dynamic programming equations of Bellman, in contrast to explicit dual control methods that artificially induce probing into the control law by modifying the cost function to include a term that rewards learning. The proposed implicit dual control approach is novel in that it combines a particle filter with a policy-iteration method for forward dynamic programming. The integration of the two methods provides a complete sampling-based approach to the problem. Implementation of the approach is simplified by making use of a specific architecture denoted as an H-block. Practical suggestions are given for reducing computational loads within the H-block for real-time applications. As an example, the method is applied to the control of a stochastic pendulum model having unknown mass, length, initial position and velocity, and unknown sign of its dc gain. Simulation results indicate that active controllers based on the described method can systematically improve closed-loop performance with respect to other more common stochastic control approaches.

Estimation of affinities of ligands in mixtures via magnetic recovery of target-ligand complexes and chromatographic analyses: chemometrics and an experimental model

PubMed Central

2011-01-01

Abstract Background The combinatorial library strategy of using multiple candidate ligands in mixtures as library members is ideal in terms of cost and efficiency, but needs special screening methods to estimate the affinities of candidate ligands in such mixtures. Herein, a new method to screen candidate ligands present in unknown molar quantities in mixtures was investigated. Results The proposed method involves preparing a processed-mixture-for-screening (PMFS) with each mixture sample and an exogenous reference ligand, initiating competitive binding among ligands from the PMFS to a target immobilized on magnetic particles, recovering target-ligand complexes in equilibrium by magnetic force, extracting and concentrating bound ligands, and analyzing ligands in the PMFS and the concentrated extract by chromatography. The relative affinity of each candidate ligand to its reference ligand is estimated via an approximation equation assuming (a) the candidate ligand and its reference ligand bind to the same site(s) on the target, (b) their chromatographic peak areas are over five times their intercepts of linear response but within their linear ranges, (c) their binding ratios are below 10%. These prerequisites are met by optimizing primarily the quantity of the target used and the PMFS composition ratio. The new method was tested using the competitive binding of biotin derivatives from mixtures to streptavidin immobilized on magnetic particles as a model. Each mixture sample containing a limited number of candidate biotin derivatives with moderate differences in their molar quantities were prepared via parallel-combinatorial-synthesis (PCS) without purification, or via the pooling of individual compounds. Some purified biotin derivatives were used as reference ligands. This method showed resistance to variations in chromatographic quantification sensitivity and concentration ratios; optimized conditions to validate the approximation equation could be applied to different mixture samples. Relative affinities of candidate biotin derivatives with unknown molar quantities in each mixture sample were consistent with those estimated by a homogenous method using their purified counterparts as samples. Conclusions This new method is robust and effective for each mixture possessing a limited number of candidate ligands whose molar quantities have moderate differences, and its integration with PCS has promise to routinely practice the mixture-based library strategy. PMID:21545719

Brain Regions Influencing Implicit Violent Attitudes: A Lesion-Mapping Study.

PubMed

Cristofori, Irene; Zhong, Wanting; Mandoske, Valerie; Chau, Aileen; Krueger, Frank; Strenziok, Maren; Grafman, Jordan

2016-03-02

Increased aggression is common after traumatic brain injuries and may persist after cognitive recovery. Maladaptive aggression and violence are associated with dysfunction in the prefrontal and temporal cortex, but such dysfunctional behaviors are typically measured by explicit scales and history. However, it is well known that answers on explicit scales on sensitive topics--such as aggressive thoughts and behaviors--may not reveal true tendencies. Here, we investigated the neural basis of implicit attitudes toward aggression in humans using a modified version of the Implicit Association Task (IAT) with a unique sample of 112 Vietnam War veterans who suffered penetrating brain injury and 33 healthy controls who also served in combat in Vietnam but had no history of brain injury. We hypothesized that dorsolateral prefrontal cortex (dlPFC) lesions, due to the crucial role of the dlPFC in response inhibition, could influence performance on the IAT. In addition, we investigated the causal contribution of specific brain areas to implicit attitudes toward violence. We found a more positive implicit attitude toward aggression among individuals with lesions to the dlPFC and inferior posterior temporal cortex (ipTC). Furthermore, executive functions were critically involved in regulating implicit attitudes toward violence and aggression. Our findings complement existing evidence on the neural basis of explicit aggression centered on the ventromedial prefrontal cortex. These findings highlight that dlPFC and ipTC play a causal role in modulating implicit attitudes about violence and are crucially involved in the pathogenesis of aggressive behavior. Maladaptive aggression and violence can lead to interpersonal conflict and criminal behavior. Surprisingly little is known about implicit attitudes toward violence and aggression. Here, we used a range of techniques, including voxel-based lesion-symptom mapping, to examine the causal role of brain structures underpinning implicit attitudes toward aggression in a unique sample of combat veterans with traumatic brain injury. We found that damage to the dorsolateral prefrontal cortex (dlPFC) led to a more positive implicit attitude toward violence that under most normal situations would be considered inappropriate. These results suggest that treatments aimed at increasing cognitive control using cognitive behavioral therapies dependent on the intact dlPFC could treat aggressive and violent behavior. Copyright © 2016 the authors 0270-6474/16/362757-12$15.00/0.

Medical School Experiences Associated with Change in Implicit Racial Bias Among 3547 Students: A Medical Student CHANGES Study Report.

PubMed

van Ryn, Michelle; Hardeman, Rachel; Phelan, Sean M; Burgess, Diana J; Dovidio, John F; Herrin, Jeph; Burke, Sara E; Nelson, David B; Perry, Sylvia; Yeazel, Mark; Przedworski, Julia M

2015-12-01

Physician implicit (unconscious, automatic) bias has been shown to contribute to racial disparities in medical care. The impact of medical education on implicit racial bias is unknown. To examine the association between change in student implicit racial bias towards African Americans and student reports on their experiences with 1) formal curricula related to disparities in health and health care, cultural competence, and/or minority health; 2) informal curricula including racial climate and role model behavior; and 3) the amount and favorability of interracial contact during school. Prospective observational study involving Web-based questionnaires administered during first (2010) and last (2014) semesters of medical school. A total of 3547 students from a stratified random sample of 49 U.S. medical schools. Change in implicit racial attitudes as assessed by the Black-White Implicit Association Test administered during the first semester and again during the last semester of medical school. In multivariable modeling, having completed the Black-White Implicit Association Test during medical school remained a statistically significant predictor of decreased implicit racial bias (-5.34, p ≤ 0.001: mixed effects regression with random intercept across schools). Students' self-assessed skills regarding providing care to African American patients had a borderline association with decreased implicit racial bias (-2.18, p = 0.056). Having heard negative comments from attending physicians or residents about African American patients (3.17, p = 0.026) and having had unfavorable vs. very favorable contact with African American physicians (18.79, p = 0.003) were statistically significant predictors of increased implicit racial bias. Medical school experiences in all three domains were independently associated with change in student implicit racial attitudes. These findings are notable given that even small differences in implicit racial attitudes have been shown to affect behavior and that implicit attitudes are developed over a long period of repeated exposure and are difficult to change.

Attitudes towards individuals with disabilities as measured by the implicit association test: a literature review.

PubMed

Wilson, Michelle Clare; Scior, Katrina

2014-02-01

Research investigating attitudes towards individuals with disabilities has largely focused on self-reported explicit attitudes. Given that factors such as social desirability may influence explicit attitudes, researchers have developed tools which instead assess less consciously controllable implicit attitudes. Considering research on implicit attitudes thus seems pertinent. A review of studies measuring implicit attitudes towards individuals with physical disabilities (visual, motor or hearing) or intellectual disabilities via the Implicit Association Test (IAT; Greenwald, McGhee, & Schwartz, 1998) was carried out. Systematic searches of PsycINFO, CINAHL, EMBASE, ERIC, MEDLINE, PUBMED, Scopus and Web of Science databases identified relevant articles published between January 2000 and September 2012. Seventeen articles (reporting on 18 studies that employed the IAT) were identified. These investigated implicit attitudes towards individuals with; physical disabilities (N=13), intellectual disabilities (N=3), both physical and intellectual disabilities (N=1), and 'unspecified disabilities' (N=1). Across all studies, moderate to strong negative implicit attitudes were found and there was little to no association between explicit and implicit attitudes. Individuals' beliefs about the controllability of their future, sensitivity to the concept of disease, and contact with individuals with disabilities appear to be associated with implicit attitudes. A consistent pattern of moderate to strong negative implicit attitudes towards individuals with disabilities was evident. These studies provide a starting point, but methodological issues related to sampling and the employed IATs limit the generalizability of these results. Further research investigating implicit attitudes towards specific disability types, with a wider subject pool are necessary as well as further investigation of factors that contribute to these attitudes. Copyright © 2013 Elsevier Ltd. All rights reserved.

Improving the Efficiency of Non-equilibrium Sampling in the Aqueous Environment via Implicit-Solvent Simulations.

PubMed

Liu, Hui; Chen, Fu; Sun, Huiyong; Li, Dan; Hou, Tingjun

2017-04-11

By means of estimators based on non-equilibrium work, equilibrium free energy differences or potentials of mean force (PMFs) of a system of interest can be computed from biased molecular dynamics (MD) simulations. The approach, however, is often plagued by slow conformational sampling and poor convergence, especially when the solvent effects are taken into account. Here, as a possible way to alleviate the problem, several widely used implicit-solvent models, which are derived from the analytic generalized Born (GB) equation and implemented in the AMBER suite of programs, were employed in free energy calculations based on non-equilibrium work and evaluated for their abilities to emulate explicit water. As a test case, pulling MD simulations were carried out on an alanine polypeptide with different solvent models and protocols, followed by comparisons of the reconstructed PMF profiles along the unfolding coordinate. The results show that when employing the non-equilibrium work method, sampling with an implicit-solvent model is several times faster and, more importantly, converges more rapidly than that with explicit water due to reduction of dissipation. Among the assessed GB models, the Neck variants outperform the OBC and HCT variants in terms of accuracy, whereas their computational costs are comparable. In addition, for the best-performing models, the impact of the solvent-accessible surface area (SASA) dependent nonpolar solvation term was also examined. The present study highlights the advantages of implicit-solvent models for non-equilibrium sampling.

High throughput screening of ligand binding to macromolecules using high resolution powder diffraction

DOEpatents

Von Dreele, Robert B.; D'Amico, Kevin

2006-10-31

A process is provided for the high throughput screening of binding of ligands to macromolecules using high resolution powder diffraction data including producing a first sample slurry of a selected polycrystalline macromolecule material and a solvent, producing a second sample slurry of a selected polycrystalline macromolecule material, one or more ligands and the solvent, obtaining a high resolution powder diffraction pattern on each of said first sample slurry and the second sample slurry, and, comparing the high resolution powder diffraction pattern of the first sample slurry and the high resolution powder diffraction pattern of the second sample slurry whereby a difference in the high resolution powder diffraction patterns of the first sample slurry and the second sample slurry provides a positive indication for the formation of a complex between the selected polycrystalline macromolecule material and at least one of the one or more ligands.

Explicit Not Implicit Preferences Predict Conservation Intentions for Endangered Species and Biomes.

PubMed

Echeverri, Alejandra; Callahan, Megan M; Chan, Kai M A; Satterfield, Terre; Zhao, Jiaying

2017-01-01

Conservation of biodiversity is determined in part by human preferences. Preferences relevant to conservation have been examined largely via explicit measures (e.g., a self-reported degree of liking), with implicit measures (e.g., preconscious, automatic evaluations) receiving relatively less attention. This is the case despite psychological evidence from other contexts that implicit preferences are more informative of behavior. Thus, the type of measure that predicts conservation intentions for biodiversity is unknown. We conducted three studies to examine conservation intentions in light of people's explicit and implicit preferences toward four endangered species (sea otter, American badger, caribou, yellow-breasted chat) and four biomes (forest, ocean, grassland, tundra). In Study 1 (n = 55), we found that people implicitly preferred caribou most, but explicitly preferred sea otter most, with a significant multiple regression where participants' explicit preferences dictated their stated intended donations for conservation of each species. In Study 2 (n = 57) we found that people implicitly and explicitly preferred forest and ocean over grassland and tundra. Explicit rather than implicit preferences predicted the intended donation for conservation of the ocean biome. Study 3 involved a broader online sample of participants (n = 463) and also found that explicit preferences dictated the intended donations for conservation of biomes and species. Our findings reveal discrepancies between implicit and explicit preferences toward species, but not toward biomes. Importantly, the results demonstrate that explicit rather than implicit preferences predict conservation intentions for biodiversity. The current findings have several implications for conservation and the communication of biodiversity initiatives.

Implicit affective evaluation bias in hypochondriasis: findings from the Affect Misattribution Procedure.

PubMed

Schreiber, Franziska; Neng, Julia M B; Heimlich, Christiane; Witthöft, Michael; Weck, Florian

2014-10-01

Cognitive theories of hypochondriasis (HYP) suggest that catastrophic misinterpretations of benign body sensations are a core feature for the maintenance of the disorder. There is tentative support from an analog sample that the interpretation of illness-related information also involves an implicit affective component. This is the first study to examine this negative affective evaluation bias implicitly in patients with HYP. An adapted version of the Affect Misattribution Procedure (AMP) with illness, symptom and neutral primes was used in 80 patients with HYP, and compared to 83 patients with an anxiety disorder (AD), as well as 90 healthy controls (CG). The HYP group showed significantly more negative affective reactions in illness prime trials, compared to both control groups, as well as more negative implicit evaluations on symptom prime trials, compared to the CG. Significant inverse relationships were observed only between the implicit evaluations of illness words and health anxiety questionnaires. Thus, an implicit negative affective evaluation bias of serious illnesses rather than symptoms is a unique feature of HYP. Copyright © 2014 Elsevier Ltd. All rights reserved.

Borderline Personality Features and Implicit Shame-Prone Self-Concept in Middle Childhood and Early Adolescence

ERIC Educational Resources Information Center

Hawes, David J.; Helyer, Rebekah; Herlianto, Eugene C.; Willing, Jonah

2013-01-01

This study tested if children and adolescents with high levels of borderline personality features (BPF) exhibit the same shame-prone self-concept previously found to characterize adults with borderline personality disorder (Rusch et al., 2007). Self-concept was indexed using the Implicit Association Test, in a community sample of…

New Zealand = Maori, New Zealand = Bicultural: Ethnic Group Differences in a National Sample of Maori and Europeans

ERIC Educational Resources Information Center

Harding, Jessica F.; Sibley, Chris G.; Robertson, Andrew

2011-01-01

New Zealand (NZ) Europeans show a unique implicit bicultural effect, with research using the Implicit Association Test consistently showing that they associate Maori (the Indigenous peoples) and their own (dominant/advantaged majority) group as equally representative of the nation. We replicated and extended this NZ = bicultural effect in a small…

Implicit and Explicit Attitudes Predict Smoking Cessation: Moderating Effects of Experienced Failure to Control Smoking and Plans to Quit

PubMed Central

Chassin, Laurie; Presson, Clark C.; Sherman, Steven J.; Seo, Dong-Chul; Macy, Jon

2010-01-01

The current study tested implicit and explicit attitudes as prospective predictors of smoking cessation in a Midwestern community sample of smokers. Results showed that the effects of attitudes significantly varied with levels of experienced failure to control smoking and plans to quit. Explicit attitudes significantly predicted later cessation among those with low (but not high or average) levels of experienced failure to control smoking. Conversely, however, implicit attitudes significantly predicted later cessation among those with high levels of experienced failure to control smoking, but only if they had a plan to quit. Because smoking cessation involves both controlled and automatic processes, interventions may need to consider attitude change interventions that focus on both implicit and explicit attitudes. PMID:21198227

Theoretical restrictions on longest implicit time scales in Markov state models of biomolecular dynamics

NASA Astrophysics Data System (ADS)

Sinitskiy, Anton V.; Pande, Vijay S.

2018-01-01

Markov state models (MSMs) have been widely used to analyze computer simulations of various biomolecular systems. They can capture conformational transitions much slower than an average or maximal length of a single molecular dynamics (MD) trajectory from the set of trajectories used to build the MSM. A rule of thumb claiming that the slowest implicit time scale captured by an MSM should be comparable by the order of magnitude to the aggregate duration of all MD trajectories used to build this MSM has been known in the field. However, this rule has never been formally proved. In this work, we present analytical results for the slowest time scale in several types of MSMs, supporting the above rule. We conclude that the slowest implicit time scale equals the product of the aggregate sampling and four factors that quantify: (1) how much statistics on the conformational transitions corresponding to the longest implicit time scale is available, (2) how good the sampling of the destination Markov state is, (3) the gain in statistics from using a sliding window for counting transitions between Markov states, and (4) a bias in the estimate of the implicit time scale arising from finite sampling of the conformational transitions. We demonstrate that in many practically important cases all these four factors are on the order of unity, and we analyze possible scenarios that could lead to their significant deviation from unity. Overall, we provide for the first time analytical results on the slowest time scales captured by MSMs. These results can guide further practical applications of MSMs to biomolecular dynamics and allow for higher computational efficiency of simulations.

Suicide and Self-Injury-Related Implicit Cognition: A Large-Scale Examination and Replication

PubMed Central

Glenn, Jeffrey J.; Werntz, Alexandra J.; Slama, S. J. Katarina; Steinman, Shari A.; Teachman, Bethany A.; Nock, Matthew K.

2016-01-01

Suicide and self-injury are difficult to predict because at-risk individuals are often unable or unwilling to report their intentions. Therefore, tools to reliably assess risk without reliance on self-report are critically needed. Prior research suggests that people who engage in suicidal and nonsuicidal self-injury often implicitly (i.e., outside conscious control) associate themselves with self-harm and death, indicating that self-harm-related implicit cognition may serve as a useful behavioral marker for suicide risk. However, earlier studies left several critical questions about the robustness, sensitivity, and specificity of self-harm-related implicit associations unaddressed. We recruited a large sample of participants (N=7,015) via a public web-based platform called Project Implicit Mental Health to test several hypotheses about self-harm-related implicit associations using the Implicit Association Test (IAT). Participants were randomly assigned to complete one of three self-harm IATs (Self + Cutting using picture stimuli, Self + Suicide using word stimuli, Self + Death using word stimuli). Results replicated prior studies demonstrating that self-harm-related implicit associations were stronger among individuals with (vs. without) a history of suicide attempt and nonsuicidal self-injury. Results also suggested that self-harm-related implicit associations are robust (based on internal replication), are sensitive to recency and severity of self-harm history (e.g., stronger associations for more recent and more lethal prior suicide attempts), and correlate with specific types of self-harm behaviors. These findings clarify the nature of self-harm-related implicit cognition and highlight the IAT's potential to track current risk for specific types of self-harm in ways that more fixed risk factors cannot. PMID:27991808

How to deal with multiple binding poses in alchemical relative protein-ligand binding free energy calculations.

PubMed

Kaus, Joseph W; Harder, Edward; Lin, Teng; Abel, Robert; McCammon, J Andrew; Wang, Lingle

2015-06-09

Recent advances in improved force fields and sampling methods have made it possible for the accurate calculation of protein–ligand binding free energies. Alchemical free energy perturbation (FEP) using an explicit solvent model is one of the most rigorous methods to calculate relative binding free energies. However, for cases where there are high energy barriers separating the relevant conformations that are important for ligand binding, the calculated free energy may depend on the initial conformation used in the simulation due to the lack of complete sampling of all the important regions in phase space. This is particularly true for ligands with multiple possible binding modes separated by high energy barriers, making it difficult to sample all relevant binding modes even with modern enhanced sampling methods. In this paper, we apply a previously developed method that provides a corrected binding free energy for ligands with multiple binding modes by combining the free energy results from multiple alchemical FEP calculations starting from all enumerated poses, and the results are compared with Glide docking and MM-GBSA calculations. From these calculations, the dominant ligand binding mode can also be predicted. We apply this method to a series of ligands that bind to c-Jun N-terminal kinase-1 (JNK1) and obtain improved free energy results. The dominant ligand binding modes predicted by this method agree with the available crystallography, while both Glide docking and MM-GBSA calculations incorrectly predict the binding modes for some ligands. The method also helps separate the force field error from the ligand sampling error, such that deviations in the predicted binding free energy from the experimental values likely indicate possible inaccuracies in the force field. An error in the force field for a subset of the ligands studied was identified using this method, and improved free energy results were obtained by correcting the partial charges assigned to the ligands. This improved the root-mean-square error (RMSE) for the predicted binding free energy from 1.9 kcal/mol with the original partial charges to 1.3 kcal/mol with the corrected partial charges.

How To Deal with Multiple Binding Poses in Alchemical Relative Protein–Ligand Binding Free Energy Calculations

PubMed Central

2016-01-01

Recent advances in improved force fields and sampling methods have made it possible for the accurate calculation of protein–ligand binding free energies. Alchemical free energy perturbation (FEP) using an explicit solvent model is one of the most rigorous methods to calculate relative binding free energies. However, for cases where there are high energy barriers separating the relevant conformations that are important for ligand binding, the calculated free energy may depend on the initial conformation used in the simulation due to the lack of complete sampling of all the important regions in phase space. This is particularly true for ligands with multiple possible binding modes separated by high energy barriers, making it difficult to sample all relevant binding modes even with modern enhanced sampling methods. In this paper, we apply a previously developed method that provides a corrected binding free energy for ligands with multiple binding modes by combining the free energy results from multiple alchemical FEP calculations starting from all enumerated poses, and the results are compared with Glide docking and MM-GBSA calculations. From these calculations, the dominant ligand binding mode can also be predicted. We apply this method to a series of ligands that bind to c-Jun N-terminal kinase-1 (JNK1) and obtain improved free energy results. The dominant ligand binding modes predicted by this method agree with the available crystallography, while both Glide docking and MM-GBSA calculations incorrectly predict the binding modes for some ligands. The method also helps separate the force field error from the ligand sampling error, such that deviations in the predicted binding free energy from the experimental values likely indicate possible inaccuracies in the force field. An error in the force field for a subset of the ligands studied was identified using this method, and improved free energy results were obtained by correcting the partial charges assigned to the ligands. This improved the root-mean-square error (RMSE) for the predicted binding free energy from 1.9 kcal/mol with the original partial charges to 1.3 kcal/mol with the corrected partial charges. PMID:26085821

The unconscious pursuit of emotion regulation: Implications for psychological health

PubMed Central

Hopp, Henrik; Troy, Allison S.; Mauss, Iris B.

2012-01-01

Because of the central involvement of emotion regulation in psychological health and the role that implicit (largely unconscious) processes appear to play in emotion regulation, implicit emotion-regulatory processes should play a vital role in psychological health. We hypothesised that implicitly valuing emotion regulation translates into better psychological health in individuals who use adaptive emotion-regulation strategies. A community sample of 222 individuals (56% women) who had recently experienced a stressful life event completed an implicit measure of emotion regulation valuing (ER-IAT) and reported on their habitual use of an important adaptive emotion-regulation strategy: cognitive reappraisal. We measured three domains of psychological health: well-being, depressive symptoms, and social adjustment. As hypothesised, individuals who implicitly valued emotion regulation exhibited greater levels of psychological health, but only when they were high in cognitive reappraisal use. These findings suggest that salutary effects of unconscious emotion-regulation processes depend on its interplay with conscious emotion-regulation processes. PMID:21432692

Examining Implicit and Explicit Evaluations of Sexual Aggression and Sexually Aggressive Behavior in Men Recruited Online.

PubMed

Hermann, Chantal A; Nunes, Kevin L; Maimone, Sacha

2016-12-05

The purpose of the current study was to explore the relationship between implicit and explicit evaluations of sexual aggression and indicators of sexually aggressive behavior in samples of students and community men recruited online. Participants were male undergraduate students recruited online from a Canadian University (N = 150) and men recruited from the community via an online panel (N = 378). Participants completed measures of implicit and explicit evaluations of sexual aggression, cognitive distortions regarding rape, self-reported past sexually aggressive behavior, and self-reported proclivity to commit sexually aggressive behavior. We found that more positive explicit evaluations and more cognitive distortions were moderately to strongly associated with sexual aggression; however, this was not the case for implicit evaluations of rape. Our results suggest that explicit evaluations of sexual aggression and cognitive distortions may be relevant for understanding sexual aggression against adults, and that more research is needed exploring whether or not implicit evaluations are associated with sexually aggressive behavior. © The Author(s) 2016.

Explicit versus implicit social cognition testing in autism spectrum disorder.

PubMed

Callenmark, Björn; Kjellin, Lars; Rönnqvist, Louise; Bölte, Sven

2014-08-01

Although autism spectrum disorder is defined by reciprocal social-communication impairments, several studies have found no evidence for altered social cognition test performance. This study examined explicit (i.e. prompted) and implicit (i.e. spontaneous) variants of social cognition testing in autism spectrum disorder. A sample of 19 adolescents with autism spectrum disorder and 19 carefully matched typically developing controls completed the Dewey Story Test. 'Explicit' (multiple-choice answering format) and 'implicit' (free interview) measures of social cognition were obtained. Autism spectrum disorder participants did not differ from controls regarding explicit social cognition performance. However, the autism spectrum disorder group performed more poorly than controls on implicit social cognition performance in terms of spontaneous perspective taking and social awareness. Findings suggest that social cognition alterations in autism spectrum disorder are primarily implicit in nature and that an apparent absence of social cognition difficulties on certain tests using rather explicit testing formats does not necessarily mean social cognition typicality in autism spectrum disorder. © The Author(s) 2013.

Measuring the bias against low-income country research: an Implicit Association Test.

PubMed

Harris, Matthew; Macinko, James; Jimenez, Geronimo; Mullachery, Pricila

2017-11-06

With an increasing array of innovations and research emerging from low-income countries there is a growing recognition that even high-income countries could learn from these contexts. It is well known that the source of a product influences perception of that product, but little research has examined whether this applies also in evidence-based medicine and decision-making. In order to examine likely barriers to learning from low-income countries, this study uses established methods in cognitive psychology to explore whether healthcare professionals and researchers implicitly associate good research with rich countries more so than with poor countries. Computer-based Implicit Association Test (IAT) distributed to healthcare professionals and researchers. Stimuli representing Rich Countries were chosen from OECD members in the top ten (>$36,000 per capita) World Bank rankings and Poor Countries were chosen from the bottom thirty (<$1000 per capita) countries by GDP per capita, in both cases giving attention to regional representation. Stimuli representing Research were descriptors of the motivation (objective/biased), value (useful/worthless), clarity (precise/vague), process (transparent/dishonest), and trustworthiness (credible/unreliable) of research. IAT results are presented as a Cohen's d statistic. Quantile regression was used to assess the contribution of covariates (e.g. age, sex, country of origin) to different values of IAT responses that correspond to different levels of implicit bias. Poisson regression was used to model dichotomized responses to the explicit bias item. Three hundred twenty one tests were completed in a four-week period between March and April 2015. The mean Implicit Association Test result (a standardized mean relative latency between congruent and non-congruent categories) for the sample was 0.57 (95% CI 0.52 to 0.61) indicating that on average our sample exhibited moderately strong implicit associations between Rich Countries and Good Research. People over 40 years of age were less likely to exhibit pro-poor implicit associations, and being a peer reviewer contributes to a more pro-poor association. The majority of our participants associate Good Research with Rich Countries, compared to Poor Countries. Implicit associations such as these might disfavor research from poor countries in research evaluation, evidence-based medicine and diffusion of innovations.

The relationship between epistemological beliefs, implicit theories of intelligence, and self-regulated learning among Norwegian postsecondary students.

PubMed

Bråten, Ivar; Strømsø, Helge I

2005-12-01

More empirical work is needed to examine the dimensionality of personal epistemology and relations between those dimensions and motivational and strategic components of self-regulated learning. In particular, there is great need to investigate personal epistemology and its relation to self-regulated learning across cultures and academic contexts. Because the demarcation between personal epistemology and implicit theories of intelligence has been questioned, dimensions of personal epistemology should also be studied in relation to implicit theories of intelligence. The primary aim was to examine the dimensionality of personal epistemology and the relation between those dimensions and implicit theories of intelligence in the cultural context of Norwegian postsecondary education. A secondary aim was to examine the relative contribution of epistemological beliefs and theories of intelligence to motivational and strategic components of self-regulated learning in different academic contexts within that culture. The first sample included 178 business administration students in a traditional transmission-oriented instructional context; the second, 108 student teachers in an innovative pedagogical context. The dimensionality of the Schommer Epistemological Questionnaire was examined through factor analyses, and the resulting dimensions were examined in relation to implicit theories of intelligence. We performed multiple regression analyses, separately for the two academic contexts, to try to predict motivational (i.e. self-efficacy beliefs, mastery goal orientation, and interest) and strategic (i.e. self-regulatory strategy use) components of self-regulated learning with epistemological beliefs and implicit theories of intelligence. Considerable cross-cultural generalizability was found for the dimensionality of personal epistemology. Moreover, the dimensions of personal epistemology seemed to represent constructs separate from the construct of implicit theories of intelligence. Differences in the predictability of the epistemological dimensions were found for the two samples. For the student teachers, belief about knowledge construction and modification was a better predictor of self-regulated learning. For the business administration students, belief about the certainty of knowledge played a more important role in self-regulated learning. Epistemological beliefs predict self-regulated learning among Norwegian postsecondary students and play more important roles than implicit theories of intelligence. Relations between epistemological beliefs and self-regulated learning may vary with academic context.

Predicting hydration free energies with a hybrid QM/MM approach: an evaluation of implicit and explicit solvation models in SAMPL4

NASA Astrophysics Data System (ADS)

König, Gerhard; Pickard, Frank C.; Mei, Ye; Brooks, Bernard R.

2014-03-01

The correct representation of solute-water interactions is essential for the accurate simulation of most biological phenomena. Several highly accurate quantum methods are available to deal with solvation by using both implicit and explicit solvents. So far, however, most evaluations of those methods were based on a single conformation, which neglects solute entropy. Here, we present the first test of a novel approach to determine hydration free energies that uses molecular mechanics (MM) to sample phase space and quantum mechanics (QM) to evaluate the potential energies. Free energies are determined by using re-weighting with the Non-Boltzmann Bennett (NBB) method. In this context, the method is referred to as QM-NBB. Based on snapshots from MM sampling and accounting for their correct Boltzmann weight, it is possible to obtain hydration free energies that incorporate the effect of solute entropy. We evaluate the performance of several QM implicit solvent models, as well as explicit solvent QM/MM for the blind subset of the SAMPL4 hydration free energy challenge. While classical free energy simulations with molecular dynamics give root mean square deviations (RMSD) of 2.8 and 2.3 kcal/mol, the hybrid approach yields an improved RMSD of 1.6 kcal/mol. By selecting an appropriate functional and basis set, the RMSD can be reduced to 1 kcal/mol for calculations based on a single conformation. Results for a selected set of challenging molecules imply that this RMSD can be further reduced by using NBB to reweight MM trajectories with the SMD implicit solvent model.

Teachers' Implicit Theories of Learning to Read: A Cross-Cultural Study in Ibero-American Countries

ERIC Educational Resources Information Center

Jiménez, Juan E.; Rodríguez, Cristina; Suárez, Natalia; O'Shanahan, Isabel; Villadiego, Yalov; Uribe, Claudia; Villalobos, Jose Angel; Rodas, Patricia

2015-01-01

The main goal of this study was to explore the nature and structure of implicit theories of Spanish-speaking in-service teachers on learning to read. The study sample consisted of 591 in-service teachers from various Ibero-American countries (Spain, Mexico, Guatemala, Colombia, and Ecuador). The study analyzed attributional structure or teacher…

Assessing the Implicit Theory of Willpower for Strenuous Mental Activities Scale: Multigroup, across-gender, and cross-cultural measurement invariance and convergent and divergent validity.

PubMed

Napolitano, Christopher M; Job, Veronika

2018-05-21

Why do some people struggle with self-control (colloquially called willpower) whereas others are able to sustain it during challenging circumstances? Recent research showed that a person's implicit theories of willpower-whether they think self-control capacity is a limited or nonlimited resource-predict sustained self-control on laboratory tasks and on goal-related outcomes in everyday life. The present research tests the Implicit Theory of Willpower for Strenuous Mental Activities Scale (or ITW-M) Scale for measurement invariance across samples and gender within each culture, and two cultural contexts (the U.S. and Switzerland/Germany). Across a series of multigroup confirmatory factor analyses, we found support for the measurement invariance of the ITW-M scale across samples within and across two cultures, as well as across men and women. Further, the analyses showed expected patterns of convergent (with life-satisfaction and trait-self-control) and discriminant validity (with implicit theory of intelligence). These results provide guidelines for future research and clinical practice using the ITW-M scale for the investigation of latent group differences, for example, between gender or cultures. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

SKATE: a docking program that decouples systematic sampling from scoring.

PubMed

Feng, Jianwen A; Marshall, Garland R

2010-11-15

SKATE is a docking prototype that decouples systematic sampling from scoring. This novel approach removes any interdependence between sampling and scoring functions to achieve better sampling and, thus, improves docking accuracy. SKATE systematically samples a ligand's conformational, rotational and translational degrees of freedom, as constrained by a receptor pocket, to find sterically allowed poses. Efficient systematic sampling is achieved by pruning the combinatorial tree using aggregate assembly, discriminant analysis, adaptive sampling, radial sampling, and clustering. Because systematic sampling is decoupled from scoring, the poses generated by SKATE can be ranked by any published, or in-house, scoring function. To test the performance of SKATE, ligands from the Asetex/CDCC set, the Surflex set, and the Vertex set, a total of 266 complexes, were redocked to their respective receptors. The results show that SKATE was able to sample poses within 2 A RMSD of the native structure for 98, 95, and 98% of the cases in the Astex/CDCC, Surflex, and Vertex sets, respectively. Cross-docking accuracy of SKATE was also assessed by docking 10 ligands to thymidine kinase and 73 ligands to cyclin-dependent kinase. 2010 Wiley Periodicals, Inc.

Passing thoughts on the evolutionary stability of implicit motor behaviour: performance retention under physiological fatigue.

PubMed

Poolton, J M; Masters, R S W; Maxwell, J P

2007-06-01

Heuristics of evolutionary biology (e.g., survival of the fittest) dictate that phylogenetically older processes are inherently more stable and resilient to disruption than younger processes. On the grounds that non-declarative behaviour emerged long before declarative behaviour, Reber (1992) argues that implicit (non-declarative) learning is supported by neural processes that are evolutionarily older than those supporting explicit learning. Reber suggested that implicit learning thus leads to performance that is more robust than explicit learning. Applying this evolutionary framework to motor performance, we examined whether implicit motor learning, relative to explicit motor learning, conferred motor output that was resilient to physiological fatigue and durable over time. In Part One of the study a fatigued state was induced by a double Wingate Anaerobic test protocol. Fatigue had no affect on performance of participants in the implicit condition; whereas, performance of participants in the explicit condition deteriorated significantly. In Part Two of the study a convenience sample of participants was recalled following a one-year hiatus. In both the implicit and the explicit condition retention of performance was seen and, contrary to the findings in Part One, so was resilience to fatigue. The resilient performance in the explicit condition after one year may have resulted from forgetting (the decay of declarative knowledge) or from consolidation of declarative knowledge as implicit memories. In either case, implicit processes were left to more effectively support motor performance.

Modeling stimulus variation in three common implicit attitude tasks.

PubMed

Wolsiefer, Katie; Westfall, Jacob; Judd, Charles M

2017-08-01

We explored the consequences of ignoring the sampling variation due to stimuli in the domain of implicit attitudes. A large literature in psycholinguistics has examined the statistical treatment of random stimulus materials, but the recommendations from this literature have not been applied to the social psychological literature on implicit attitudes. This is partly because of inherent complications in applying crossed random-effect models to some of the most common implicit attitude tasks, and partly because no work to date has demonstrated that random stimulus variation is in fact consequential in implicit attitude measurement. We addressed this problem by laying out statistically appropriate and practically feasible crossed random-effect models for three of the most commonly used implicit attitude measures-the Implicit Association Test, affect misattribution procedure, and evaluative priming task-and then applying these models to large datasets (average N = 3,206) that assess participants' implicit attitudes toward race, politics, and self-esteem. We showed that the test statistics from the traditional analyses are substantially (about 60 %) inflated relative to the more-appropriate analyses that incorporate stimulus variation. Because all three tasks used the same stimulus words and faces, we could also meaningfully compare the relative contributions of stimulus variation across the tasks. In an appendix, we give syntax in R, SAS, and SPSS for fitting the recommended crossed random-effects models to data from all three tasks, as well as instructions on how to structure the data file.

Evaluation of DNA Force Fields in Implicit Solvation

PubMed Central

Gaillard, Thomas; Case, David A.

2011-01-01

DNA structural deformations and dynamics are crucial to its interactions in the cell. Theoretical simulations are essential tools to explore the structure, dynamics, and thermodynamics of biomolecules in a systematic way. Molecular mechanics force fields for DNA have benefited from constant improvements during the last decades. Several studies have evaluated and compared available force fields when the solvent is modeled by explicit molecules. On the other hand, few systematic studies have assessed the quality of duplex DNA models when implicit solvation is employed. The interest of an implicit modeling of the solvent consists in the important gain in the simulation performance and conformational sampling speed. In this study, respective influences of the force field and the implicit solvation model choice on DNA simulation quality are evaluated. To this end, extensive implicit solvent duplex DNA simulations are performed, attempting to reach both conformational and sequence diversity convergence. Structural parameters are extracted from simulations and statistically compared to available experimental and explicit solvation simulation data. Our results quantitatively expose the respective strengths and weaknesses of the different DNA force fields and implicit solvation models studied. This work can lead to the suggestion of improvements to current DNA theoretical models. PMID:22043178

Implicit and explicit attitudes predict smoking cessation: moderating effects of experienced failure to control smoking and plans to quit.

PubMed

Chassin, Laurie; Presson, Clark C; Sherman, Steven J; Seo, Dong-Chul; Macy, Jonathan T

2010-12-01

The current study tested implicit and explicit attitudes as prospective predictors of smoking cessation in a Midwestern community sample of smokers. Results showed that the effects of attitudes significantly varied with levels of experienced failure to control smoking and plans to quit. Explicit attitudes significantly predicted later cessation among those with low (but not high or average) levels of experienced failure to control smoking. Conversely, however, implicit attitudes significantly predicted later cessation among those with high levels of experienced failure to control smoking, but only if they had a plan to quit. Because smoking cessation involves both controlled and automatic processes, interventions may need to consider attitude change interventions that focus on both implicit and explicit attitudes. (PsycINFO Database Record (c) 2010 APA, all rights reserved).

Sampling, feasibility, and priors in data assimilation

DOE PAGES

Tu, Xuemin; Morzfeld, Matthias; Miller, Robert N.; ...

2016-03-01

Importance sampling algorithms are discussed in detail, with an emphasis on implicit sampling, and applied to data assimilation via particle filters. Implicit sampling makes it possible to use the data to find high-probability samples at relatively low cost, making the assimilation more efficient. A new analysis of the feasibility of data assimilation is presented, showing in detail why feasibility depends on the Frobenius norm of the covariance matrix of the noise and not on the number of variables. A discussion of the convergence of particular particle filters follows. A major open problem in numerical data assimilation is the determination ofmore » appropriate priors, a progress report on recent work on this problem is given. The analysis highlights the need for a careful attention both to the data and to the physics in data assimilation problems.« less

Stability and accuracy of metamemory in adulthood and aging: a longitudinal analysis.

PubMed

McDonald-Miszczak, L; Hertzog, C; Hultsch, D F

1995-12-01

The stability and accuracy of memory perceptions in 2 longitudinal samples was examined. Sample 1 consisted of 231 adults (22-78 years) tested twice over 2 years. Sample 2 consisted of 234 adults (55-86 years) tested 3 times over 6 years. Measures of perceived and actual memory change were obtained. A primary focus was whether perceptions of memory change stem from application of an implicit theory about aging and memory or from accurate monitoring of actual changes in performance. Individual differences in metamemory were highly stable over time. Results suggested at least some accurate monitoring of memory in Sample 2, in which actual change was greatest. However the overall pattern of results is largely consistent with predictions derived from an implicit theory hypothesis.

Comparing implicit and explicit semantic access of direct and indirect word pairs in schizophrenia to evaluate models of semantic memory.

PubMed

Neill, Erica; Rossell, Susan Lee

2013-02-28

Semantic memory deficits in schizophrenia (SZ) are profound, yet there is no research comparing implicit and explicit semantic processing in the same participant sample. In the current study, both implicit and explicit priming are investigated using direct (LION-TIGER) and indirect (LION-STRIPES; where tiger is not displayed) stimuli comparing SZ to healthy controls. Based on a substantive review (Rossell and Stefanovic, 2007) and meta-analysis (Pomarol-Clotet et al., 2008), it was predicted that SZ would be associated with increased indirect priming implicitly. Further, it was predicted that SZ would be associated with abnormal indirect priming explicitly, replicating earlier work (Assaf et al., 2006). No specific hypotheses were made for implicit direct priming due to the heterogeneity of the literature. It was hypothesised that explicit direct priming would be intact based on the structured nature of this task. The pattern of results suggests (1) intact reaction time (RT) and error performance implicitly in the face of abnormal direct priming and (2) impaired RT and error performance explicitly. This pattern confirms general findings regarding implicit/explicit memory impairments in SZ whilst highlighting the unique pattern of performance specific to semantic priming. Finally, priming performance is discussed in relation to thought disorder and length of illness. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Implicit negative affect predicts attention to sad faces beyond self-reported depressive symptoms in healthy individuals: An eye-tracking study.

PubMed

Bodenschatz, Charlott Maria; Skopinceva, Marija; Kersting, Anette; Quirin, Markus; Suslow, Thomas

2018-04-04

Cognitive theories of depression assume biased attention towards mood-congruent information as a central vulnerability and maintaining factor. Among other symptoms, depression is characterized by excessive negative affect (NA). Yet, little is known about the impact of naturally occurring NA on the allocation of attention to emotional information. The study investigates how implicit and explicit NA as well as self-reported depressive symptoms predict attentional biases in a sample of healthy individuals (N = 104). Attentional biases were assessed using eye-tracking during a free viewing task in which images of sad, angry, happy and neutral faces were shown simultaneously. Participants' implicit affectivity was measured indirectly using the Implicit Positive and Negative Affect Test. Questionnaires were administered to assess actual and habitual explicit NA and presence of depressive symptoms. Higher levels of depressive symptoms were associated with sustained attention to sad faces and reduced attention to happy faces. Implicit but not explicit NA significantly predicted gaze behavior towards sad faces independently from depressive symptoms. The present study supports the idea that naturally occurring implicit NA is associated with attention allocation to dysphoric facial expression. The findings demonstrate the utility of implicit affectivity measures in studying individual differences in depression-relevant attentional biases and cognitive vulnerability. Copyright © 2018 Elsevier B.V. All rights reserved.

Equivalent Stimuli Are More Strongly Related after Training with Delayed Matching than after Simultaneous Matching: A Study Using the Implicit Relational Assessment Procedure (IRAP)

ERIC Educational Resources Information Center

Bortoloti, Renato; de Rose, Julio C.

2012-01-01

Bortoloti and de Rose (2009) found evidence that the level of functional transfer is higher in equivalence classes generated by delayed matching to sample (DMTS) than in classes generated by simultaneous matching (SMTS). We attempted to replicate these findings with the Implicit Relational Assessment Procedure (IRAP). Two experimental groups…

Optimization of the GBMV2 implicit solvent force field for accurate simulation of protein conformational equilibria.

PubMed

Lee, Kuo Hao; Chen, Jianhan

2017-06-15

Accurate treatment of solvent environment is critical for reliable simulations of protein conformational equilibria. Implicit treatment of solvation, such as using the generalized Born (GB) class of models arguably provides an optimal balance between computational efficiency and physical accuracy. Yet, GB models are frequently plagued by a tendency to generate overly compact structures. The physical origins of this drawback are relatively well understood, and the key to a balanced implicit solvent protein force field is careful optimization of physical parameters to achieve a sufficient level of cancellation of errors. The latter has been hampered by the difficulty of generating converged conformational ensembles of non-trivial model proteins using the popular replica exchange sampling technique. Here, we leverage improved sampling efficiency of a newly developed multi-scale enhanced sampling technique to re-optimize the generalized-Born with molecular volume (GBMV2) implicit solvent model with the CHARMM36 protein force field. Recursive optimization of key GBMV2 parameters (such as input radii) and protein torsion profiles (via the CMAP torsion cross terms) has led to a more balanced GBMV2 protein force field that recapitulates the structures and stabilities of both helical and β-hairpin model peptides. Importantly, this force field appears to be free of the over-compaction bias, and can generate structural ensembles of several intrinsically disordered proteins of various lengths that seem highly consistent with available experimental data. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Assessment and Challenges of Ligand Docking into Comparative Models of G-Protein Coupled Receptors

PubMed Central

Frimurer, Thomas M.; Meiler, Jens

2013-01-01

The rapidly increasing number of high-resolution X-ray structures of G-protein coupled receptors (GPCRs) creates a unique opportunity to employ comparative modeling and docking to provide valuable insight into the function and ligand binding determinants of novel receptors, to assist in virtual screening and to design and optimize drug candidates. However, low sequence identity between receptors, conformational flexibility, and chemical diversity of ligands present an enormous challenge to molecular modeling approaches. It is our hypothesis that rapid Monte-Carlo sampling of protein backbone and side-chain conformational space with Rosetta can be leveraged to meet this challenge. This study performs unbiased comparative modeling and docking methodologies using 14 distinct high-resolution GPCRs and proposes knowledge-based filtering methods for improvement of sampling performance and identification of correct ligand-receptor interactions. On average, top ranked receptor models built on template structures over 50% sequence identity are within 2.9 Å of the experimental structure, with an average root mean square deviation (RMSD) of 2.2 Å for the transmembrane region and 5 Å for the second extracellular loop. Furthermore, these models are consistently correlated with low Rosetta energy score. To predict their binding modes, ligand conformers of the 14 ligands co-crystalized with the GPCRs were docked against the top ranked comparative models. In contrast to the comparative models themselves, however, it remains difficult to unambiguously identify correct binding modes by score alone. On average, sampling performance was improved by 103 fold over random using knowledge-based and energy-based filters. In assessing the applicability of experimental constraints, we found that sampling performance is increased by one order of magnitude for every 10 residues known to contact the ligand. Additionally, in the case of DOR, knowledge of a single specific ligand-protein contact improved sampling efficiency 7 fold. These findings offer specific guidelines which may lead to increased success in determining receptor-ligand complexes. PMID:23844000

Training Implicit Social Anxiety Associations: An Experimental Intervention

PubMed Central

Clerkin, Elise M.; Teachman, Bethany A.

2010-01-01

The current study investigates an experimental anxiety reduction intervention among a highly socially anxious sample (N=108; n=36 per Condition; 80 women). Using a conditioning paradigm, our goal was to modify implicit social anxiety associations to directly test the premise from cognitive models that biased cognitive processing may be causally related to anxious responding. Participants were trained to preferentially process non-threatening information through repeated pairings of self-relevant stimuli and faces indicating positive social feedback. As expected, participants in this positive training condition (relative to our two control conditions) displayed less negative implicit associations following training, and were more likely to complete an impromptu speech (though they did not report less anxiety during the speech). These findings offer partial support for cognitive models and indicate that implicit associations are not only correlated with social anxiety, they may be causally related to anxiety reduction as well. PMID:20102788

Training implicit social anxiety associations: an experimental intervention.

PubMed

Clerkin, Elise M; Teachman, Bethany A

2010-04-01

The current study investigates an experimental anxiety reduction intervention among a highly socially anxious sample (N=108; n=36 per Condition; 80 women). Using a conditioning paradigm, our goal was to modify implicit social anxiety associations to directly test the premise from cognitive models that biased cognitive processing may be causally related to anxious responding. Participants were trained to preferentially process non-threatening information through repeated pairings of self-relevant stimuli and faces indicating positive social feedback. As expected, participants in this positive training condition (relative to our two control conditions) displayed less negative implicit associations following training, and were more likely to complete an impromptu speech (though they did not report less anxiety during the speech). These findings offer partial support for cognitive models and indicate that implicit associations are not only correlated with social anxiety, they may be causally related to anxiety reduction as well. (c) 2010 Elsevier Ltd. All rights reserved.

Implicit finite difference methods on composite grids

NASA Technical Reports Server (NTRS)

Mastin, C. Wayne

1987-01-01

Techniques for eliminating time lags in the implicit finite-difference solution of partial differential equations are investigated analytically, with a focus on transient fluid dynamics problems on overlapping multicomponent grids. The fundamental principles of the approach are explained, and the method is shown to be applicable to both rectangular and curvilinear grids. Numerical results for sample problems are compared with exact solutions in graphs, and good agreement is demonstrated.

Exposure to graphic warning labels on cigarette packages: Effects on implicit and explicit attitudes towards smoking among young adults.

PubMed

Macy, Jonathan T; Chassin, Laurie; Presson, Clark C; Yeung, Ellen

2016-01-01

To test the effect of exposure to the US Food and Drug Administration's proposed graphic images with text warning statements for cigarette packages on implicit and explicit attitudes towards smoking. A two-session web-based study was conducted with 2192 young adults 18-25-years-old. During session one, demographics, smoking behaviour, and baseline implicit and explicit attitudes were assessed. Session two, completed on average 18 days later, contained random assignment to viewing one of three sets of cigarette packages, graphic images with text warnings, text warnings only, or current US Surgeon General's text warnings. Participants then completed post-exposure measures of implicit and explicit attitudes. ANCOVAs tested the effect of condition on the outcomes, controlling for baseline attitudes. Smokers who viewed packages with graphic images plus text warnings demonstrated more negative implicit attitudes compared to smokers in the other conditions (p = .004). For the entire sample, explicit attitudes were more negative for those who viewed graphic images plus text warnings compared to those who viewed current US Surgeon General's text warnings (p = .014), but there was no difference compared to those who viewed text-only warnings. Graphic health warnings on cigarette packages can influence young adult smokers' implicit attitudes towards smoking.

Ethnic identity and paranoid thinking: Implicit out-group preference and language dominance predict paranoia in Emirati women.

PubMed

Thomas, Justin; Bentall, Richard P; Hadden, Lowri; O'Hara, Lily

2017-09-01

Psychotic experiences including persecutory beliefs are elevated among immigrant and minority populations, especially when living in low ethnic density neighbourhoods (the ethnic density effect). Discrimination, victimization and experiencing a sense of 'not belonging' are hypothesized to play a role in this effect. Because a secure ethnic identity protects against poor self-esteem it may also protect against paranoia. This study explores the relationship between language proficiency (Arabic/English), in-group identity (implicit and explicit) and paranoia in female Emirati university students. Female citizens of the United Arab Emirates (UAE), Emirati college women (N = 208), reported English/Arabic language proficiencies, and performed a computerized affective priming task engineered to implicitly assess in-group (Emirati) versus out-group (American) positivity. Participants also completed self-report measures of in-group identity (MIIS), and paranoia (PaDs). Arabic proficiency was negatively correlated with paranoia, as was implicit in-group positivity. Furthermore, participants reporting English language dominance, and those demonstrating an implicit out-group preference, reported the highest levels of paranoia. The study is limited by its use of an all female sample. Implicit in-group attitudes and linguistic competence protect against paranoia and may help to explain the ethnic density effect. Copyright © 2016 Elsevier Ltd. All rights reserved.

Implicit attitudes to sexual partner concurrency vary by sexual orientation but not by gender-A cross sectional study of Belgian students.

PubMed

Kenyon, Chris R; Wolfs, Kenny; Osbak, Kara; van Lankveld, Jacques; Van Hal, Guido

2018-01-01

High rates of sexual partner concurrency have been shown to facilitate the spread of various sexually transmitted infections. Assessments of explicit attitudes to concurrency have however found little difference between populations. Implicit attitudes to concurrency may vary between populations and play a role in generating differences in the prevalence of concurrency. We developed a concurrency implicit associations test (C-IAT) to assess if implicit attitudes towards concurrency may vary between individuals and populations and what the correlates of these variations are. A sample of 869 Belgian students (mean age 23, SD 5.1) completed an online version of the C-IAT together with a questionnaire concerning sexual behavior and explicit attitudes to concurrency. The study participants C-IATs demonstrated a strong preference for monogamy (-0.78, SD = 0.41). 93.2% of participants had a pro-monogamy C-IAT. There was no difference in this implicit preference for monogamy between heterosexual men and women. Men who have sex with men and women who have sex with women were more likely to exhibit implicit but not explicit preferences for concurrency compared to heterosexual men and women. Correlates of the C-IAT varied between men and women.

Planar optical waveguide based sandwich assay sensors and processes for the detection of biological targets including protein markers, pathogens and cellular debris

DOEpatents

Martinez, Jennifer S [Santa Fe, NM; Swanson, Basil I [Los Alamos, NM; Grace, Karen M [Los Alamos, NM; Grace, Wynne K [Los Alamos, NM; Shreve, Andrew P [Santa Fe, NM

2009-06-02

An assay element is described including recognition ligands bound to a film on a single mode planar optical waveguide, the film from the group of a membrane, a polymerized bilayer membrane, and a self-assembled monolayer containing polyethylene glycol or polypropylene glycol groups therein and an assay process for detecting the presence of a biological target is described including injecting a biological target-containing sample into a sensor cell including the assay element, with the recognition ligands adapted for binding to selected biological targets, maintaining the sample within the sensor cell for time sufficient for binding to occur between selected biological targets within the sample and the recognition ligands, injecting a solution including a reporter ligand into the sensor cell; and, interrogating the sample within the sensor cell with excitation light from the waveguide, the excitation light provided by an evanescent field of the single mode penetrating into the biological target-containing sample to a distance of less than about 200 nanometers from the waveguide thereby exciting the fluorescent-label in any bound reporter ligand within a distance of less than about 200 nanometers from the waveguide and resulting in a detectable signal.

Meta-analytic evidence of low convergence between implicit and explicit measures of the needs for achievement, affiliation, and power

PubMed Central

Köllner, Martin G.; Schultheiss, Oliver C.

2014-01-01

The correlation between implicit and explicit motive measures and potential moderators of this relationship were examined meta-analytically, using Hunter and Schmidt's (2004) approach. Studies from a comprehensive search in PsycINFO, data sets of our research group, a literature list compiled by an expert, and the results of a request for gray literature were examined for relevance and coded. Analyses were based on 49 papers, 56 independent samples, 6151 subjects, and 167 correlations. The correlations (ρ) between implicit and explicit measures were 0.130 (CI: 0.077–0.183) for the overall relationship, 0.116 (CI: 0.050–0.182) for affiliation, 0.139 (CI: 0.080–0.198) for achievement, and 0.038 (CI: −0.055–0.131) for power. Participant age did not moderate the size of these relationships. However, a greater proportion of males in the samples and an earlier publication year were associated with larger effect sizes. PMID:25152741

Implicit Theories and Offender Representativeness in Judgments About Sexual Crime.

PubMed

Harper, Craig A; Bartels, Ross M

2018-04-01

Implicit theories structure the way people understand and respond to various human actions. Typically, people believe attributes are either fixed (entitists) or malleable (incrementalists). The present study aimed to examine (a) whether attitudes toward sexual offenders differ depending upon one's implicit theory about human nature and sexual offenders, and (b) whether implicit theories are associated with judgments made about different types of child abusers. A sample of 252 community participants was recruited. Their attitudes, implicit theories, and political orientation were assessed via self-report. One of three vignettes describing an incidence of child sexual abuse was then presented. The cases were identical except the perpetrator was either an adult male, an adult female, or a male juvenile. Participants then made judgments about the offender's deserved sentence and moral character. Entitists (across both domains) held more negative attitudes than incrementalists, although the magnitude of the difference was greatest when examining implicit theories about sexual offenders. Compared with those with an incremental theory of sexual offenders, entity theorists judged sexual offending to be more (a) indicative of the perpetrator's moral character and (b) deserving of punishment. However, scores were greater toward the adult male relative to the adult female and juvenile. The findings suggest that implicit theories about sexual offenders are domain specific. They also indicate that judgments made by those with an entity theory (about sexual offenders) are affected by whether a case is representative of a stereotypical sexual offender. Implications of the findings are discussed, along with limitations and future research.

Implicit Associations in Social Anxiety Disorder: The Effects of Comorbid Depression

PubMed Central

Wong, Judy; Morrison, Amanda S.; Heimberg, Richard G.; Goldin, Philippe R.; Gross, James J.

2014-01-01

Implicit associations of the self to concepts like “calm” have been shown to be weaker in persons with social anxiety than in non-anxious healthy controls. However, other implicit self associations, such as those to acceptance or rejection, have been less studied in social anxiety, and none of this work has been conducted with clinical samples. Furthermore, the importance of depression in these relationships has not been well investigated. We addressed these issues by administering two Implicit Association Tests (IATs; Greenwald, McGhee, & Schwartz, 1998), one examining the implicit association of self/other to anxiety/calmness and the other examining the association of self/other to rejection/acceptance, to individuals with generalized social anxiety disorder (SAD, n = 85), individuals with generalized SAD and a current or past diagnosis of major depressive disorder or current dysthymic disorder (n = 47), and non-anxious, non-depressed healthy controls (n = 44). The SAD and SAD-depression groups showed weaker implicit self-calmness associations than healthy controls, with the comorbid group showing the weakest self-calmness associations. The SAD-depression group showed the weakest implicit self-acceptance associations; no difference was found between non-depressed individuals with SAD and healthy controls. Post hoc analyses revealed that differences appeared to be driven by those with current depression. The SAD-only and SAD-depression groups did not differ in self-reported (explicit) social anxiety. The implications of these findings for the understanding of SAD-depression comorbidity and for the treatment of SAD are considered. PMID:24983794

Computational study of the free energy landscape of the miniprotein CLN025 in explicit and implicit solvent.

PubMed

Rodriguez, Alex; Mokoema, Pol; Corcho, Francesc; Bisetty, Khrisna; Perez, Juan J

2011-02-17

The prediction capabilities of atomistic simulations of peptides are hampered by different difficulties, including the reliability of force fields, the treatment of the solvent or the adequate sampling of the conformational space. In this work, we have studied the conformational profile of the 10 residue miniprotein CLN025 known to exhibit a β-hairpin in its native state to understand the limitations of implicit methods to describe solvent effects and how these may be compensated by using different force fields. For this purpose, we carried out a thorough sampling of the conformational space of CLN025 in explicit solvent using the replica exchange molecular dynamics method as a sampling technique and compared the results with simulations of the system modeled using the analytical linearized Poisson-Boltzmann (ALPB) method with three different AMBER force fields: parm94, parm96, and parm99SB. The results show the peptide to exhibit a funnel-like free energy landscape with two minima in explicit solvent. In contrast, the higher minimum nearly disappears from the energy surface when the system is studied with an implicit representation of the solvent. Moreover, the different force fields used in combination with the ALPB method do not describe the system in the same manner. The results of this work suggest that the balance between intra- and intermolecular interactions is the cause of the differences between implicit and explicit solvent simulations in this system, stressing the role of the environment to define properly the conformational profile of a peptide in solution.

Working memory moderates the effect of the integrative process of implicit and explicit autonomous motivation on academic achievement.

PubMed

Gareau, Alexandre; Gaudreau, Patrick

2017-11-01

In previous research, autonomous motivation (AM) has been found to be associated with school achievement, but the relation has been largely heterogeneous across studies. AM has typically been assessed with explicit measures such as self-report questionnaires. Recent self-determination theory (SDT) research has suggested that converging implicit and explicit measures can be taken to characterize the integrative process in SDT. Drawing from dual-process theories, we contended that explicit AM is likely to promote school achievement when it is part of an integrated cognitive system that combines easily accessible mental representations (i.e., implicit AM) and efficient executive functioning. A sample of 272 university students completed a questionnaire and a lexical decision task to assess their explicit and implicit AM, respectively, and they also completed working memory capacity measures. Grades were obtained at the end of the semester to examine the short-term prospective effect of implicit and explicit AM, working memory, and their interaction. Results of moderation analyses have provided support for a synergistic interaction in which the association between explicit AM and academic achievement was positive and significant only for individuals with high level of implicit AM. Moreover, working memory was moderating the synergistic effect of explicit and implicit AM. Explicit AM was positively associated with academic achievement for students with average-to-high levels of working memory capacity, but only if their motivation operated synergistically with high implicit AM. The integrative process thus seems to hold better proprieties for achievement than the sole effect of explicit AM. Implications for SDT are outlined. © 2017 The British Psychological Society.

Evaluating the care of general medicine inpatients: how good is implicit review?

PubMed

Hayward, R A; McMahon, L F; Bernard, A M

1993-04-01

Peer review often consists of implicit evaluations by physician reviewers of the quality and appropriateness of care. This study evaluated the ability of implicit review to measure reliably various aspects of care on a general medicine inpatient service. Retrospective review of patients' charts, using structured implicit review, of a stratified random sample of consecutive admissions to a general medicine ward. A university teaching hospital. Twelve internists were trained in structured implicit review and reviewed 675 patient admissions (with 20% duplicate reviews for a total of 846 reviews). Although inter-rater reliabilities for assessments of overall quality of care and preventable deaths (kappa = 0.5) were adequate for aggregate comparisons (for example, comparing mean ratings on two hospital wards), they were inadequate for reliable evaluations of single patients using one or two reviewers. Reviewers' agreement about most focused quality problems (for example, timeliness of diagnostic evaluation and clinical readiness at time of discharge) and about the appropriateness of hospital ancillary resource use was poor (kappa < or = 0.2). For most focused implicit measures, bias due to specific reviewers who were systematically more harsh or lenient (particularly for evaluation of resource-use appropriateness) accounted for much of the variation in reviewers' assessments, but this was not a substantial problem for the measure of overall quality. Reviewers rarely reported being unable to evaluate the quality of care because of deficiencies in documentation in the patient's chart. For assessment of overall quality and preventable deaths of general medicine inpatients, implicit review by peers had moderate degrees of reliability, but for most other specific aspects of care, physician reviewers could not agree. Implicit review was particularly unreliable at evaluating the appropriateness of hospital resource use and the patient's readiness for discharge, two areas where this type of review is often used.

Control of Energy Flow Dynamics between Tetracene Ligands and PbS Quantum Dots by Size Tuning and Ligand Coverage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kroupa, Daniel M.; Arias, Dylan H.; Blackburn, Jeffrey L.

We have prepared a series of samples with the ligand 6,13-bistri(iso-propyl)silylethynyl tetracene 2-carboxylic acid (TIPS-Tc-COOH) attached to PbS quantum dot (QD) samples of three different sizes in order to monitor and control the extent and time scales of energy flow after photoexcitation. Fast energy transfer (~1 ps) to the PbS QD occurs upon direct excitation of the ligand for all samples. The largest size QD maintains the microsecond exciton lifetime characteristic of the as-prepared oleate terminated PbS QDs. However, two smaller QD sizes with lowest exciton energies similar to or larger than the TIPS-Tc-COO- triplet energy undergo energy transfer betweenmore » QD core and ligand triplet on nanosecond to microsecond timescales. For the intermediate size QDs in particular, energy can be recycled many times between ligand and core, but the triplet remains the dominant excited species at long times, living for ~3 us for fully exchanged QDs and up to 30 us for partial ligand exchange, which is revealed as a method for controlling the triplet lifetime. A unique upconverted luminescence spectrum is observed that results from annihilation of triplets after exclusive excitation of the QD core.« less

Control of Energy Flow Dynamics between Tetracene Ligands and PbS Quantum Dots by Size Tuning and Ligand Coverage

DOE PAGES

Kroupa, Daniel M.; Arias, Dylan H.; Blackburn, Jeffrey L.; ...

2018-01-24

We have prepared a series of samples with the ligand 6,13-bistri(iso-propyl)silylethynyl tetracene 2-carboxylic acid (TIPS-Tc-COOH) attached to PbS quantum dot (QD) samples of three different sizes in order to monitor and control the extent and time scales of energy flow after photoexcitation. Fast energy transfer (~1 ps) to the PbS QD occurs upon direct excitation of the ligand for all samples. The largest size QD maintains the microsecond exciton lifetime characteristic of the as-prepared oleate terminated PbS QDs. However, two smaller QD sizes with lowest exciton energies similar to or larger than the TIPS-Tc-COO- triplet energy undergo energy transfer betweenmore » QD core and ligand triplet on nanosecond to microsecond timescales. For the intermediate size QDs in particular, energy can be recycled many times between ligand and core, but the triplet remains the dominant excited species at long times, living for ~3 us for fully exchanged QDs and up to 30 us for partial ligand exchange, which is revealed as a method for controlling the triplet lifetime. A unique upconverted luminescence spectrum is observed that results from annihilation of triplets after exclusive excitation of the QD core.« less

Ligand diffusion in proteins via enhanced sampling in molecular dynamics.

PubMed

Rydzewski, J; Nowak, W

2017-12-01

Computational simulations in biophysics describe the dynamics and functions of biological macromolecules at the atomic level. Among motions particularly important for life are the transport processes in heterogeneous media. The process of ligand diffusion inside proteins is an example of a complex rare event that can be modeled using molecular dynamics simulations. The study of physical interactions between a ligand and its biological target is of paramount importance for the design of novel drugs and enzymes. Unfortunately, the process of ligand diffusion is difficult to study experimentally. The need for identifying the ligand egress pathways and understanding how ligands migrate through protein tunnels has spurred the development of several methodological approaches to this problem. The complex topology of protein channels and the transient nature of the ligand passage pose difficulties in the modeling of the ligand entry/escape pathways by canonical molecular dynamics simulations. In this review, we report a methodology involving a reconstruction of the ligand diffusion reaction coordinates and the free-energy profiles along these reaction coordinates using enhanced sampling of conformational space. We illustrate the above methods on several ligand-protein systems, including cytochromes and G-protein-coupled receptors. The methods are general and may be adopted to other transport processes in living matter. Copyright © 2017 Elsevier B.V. All rights reserved.

Assessing bias against overweight individuals among nursing and psychology students: an implicit association test.

PubMed

Waller, Tabitha; Lampman, Claudia; Lupfer-Johnson, Gwen

2012-12-01

To determine the implicit or unconscious attitudes of Nursing and Psychology majors towards overweight individuals in medical and non-medical contexts. Obesity is a leading health concern today, which impacts both physical and psychological health. Overweight individuals confront social biases in many aspects of their lives including health care. Examining the views of Nursing and Psychology students may reveal implicit attitudes towards overweight individuals that may lead to prejudiced behaviours. A mixed design experiment with one between-subjects variable (student major: Nursing or Psychology) and one within-subjects variable (condition: congruent or incongruent) was used to assess implicit attitudes in two convenience samples of Nursing and Psychology students. A computerised implicit association test was used to determine implicit attitudes towards overweight individuals in medical and non-medical contexts. A total of 90 students from Nursing (n= 45) and Psychology (n = 45) were recruited to complete an implicit association test. Reaction times in milliseconds between the congruent trials (stereotype consistent) and incongruent trials (stereotype inconsistent) were compared with determine adherence to social stereotypes or weight bias. A statistically significant implicit bias towards overweight individuals was detected in both subject groups and in both target settings (medical vs. non-medical). Stronger weight bias was found when the stimulus targets were female than male. Findings from this study expand understanding of the implicit attitudes and social biases of Nursing and Psychology students. The views held by these future healthcare professionals may negatively impact patient care. Providing education and support to overweight individuals is central to Nursing practice in a society struggling to manage obesity. Negative stereotypes or beliefs about these individuals may result in poor patient care. Therefore, nurses and other healthcare professionals must be aware of personal biases and work to develop methods to address weight-related issues in a therapeutic manner. © 2012 Blackwell Publishing Ltd.

What Do Lead and Copper Sampling Protocols Mean, and Which Is Right for You?

EPA Science Inventory

this presentation will provide a short review of the explicit and implicit concepts behind most of the currently-used regulatory and diagnostic sampling schemes for lead, such as: random daytime sampling; automated proportional sampler; 30 minute first draw stagnation; Sequential...

Nonuniform grid implicit spatial finite difference method for acoustic wave modeling in tilted transversely isotropic media

NASA Astrophysics Data System (ADS)

Chu, Chunlei; Stoffa, Paul L.

2012-01-01

Discrete earth models are commonly represented by uniform structured grids. In order to ensure accurate numerical description of all wave components propagating through these uniform grids, the grid size must be determined by the slowest velocity of the entire model. Consequently, high velocity areas are always oversampled, which inevitably increases the computational cost. A practical solution to this problem is to use nonuniform grids. We propose a nonuniform grid implicit spatial finite difference method which utilizes nonuniform grids to obtain high efficiency and relies on implicit operators to achieve high accuracy. We present a simple way of deriving implicit finite difference operators of arbitrary stencil widths on general nonuniform grids for the first and second derivatives and, as a demonstration example, apply these operators to the pseudo-acoustic wave equation in tilted transversely isotropic (TTI) media. We propose an efficient gridding algorithm that can be used to convert uniformly sampled models onto vertically nonuniform grids. We use a 2D TTI salt model to demonstrate its effectiveness and show that the nonuniform grid implicit spatial finite difference method can produce highly accurate seismic modeling results with enhanced efficiency, compared to uniform grid explicit finite difference implementations.

Implicit theories and ability emotional intelligence

PubMed Central

Cabello, Rosario; Fernández-Berrocal, Pablo

2015-01-01

Previous research has shown that people differ in their implicit theories about the essential characteristics of intelligence and emotions. Some people believe these characteristics to be predetermined and immutable (entity theorists), whereas others believe that these characteristics can be changed through learning and behavior training (incremental theorists). The present study provides evidence that in healthy adults (N = 688), implicit beliefs about emotions and emotional intelligence (EI) may influence performance on the ability-based Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT). Adults in our sample with incremental theories about emotions and EI scored higher on the MSCEIT than entity theorists, with implicit theories about EI showing a stronger relationship to scores than theories about emotions. Although our participants perceived both emotion and EI as malleable, they viewed emotions as more malleable than EI. Women and young adults in general were more likely to be incremental theorists than men and older adults. Furthermore, we found that emotion and EI theories mediated the relationship of gender and age with ability EI. Our findings suggest that people’s implicit theories about EI may influence their emotional abilities, which may have important consequences for personal and professional EI training. PMID:26052309

The development and preliminary psychometric evaluation of an attachment Implicit Association Task.

PubMed

Venta, Amanda; Jardin, Charles; Kalpakci, Allison; Sharp, Carla

2016-01-01

The importance of measuring attachment insecurity is underscored by a vast literature tying attachment insecurity to numerous psychological disorders. Self-report measures assess explicit attachment beliefs and experiences, while interview measures, like the Adult Attachment Interview, assess implicit internal working models about the self as worthy of care and others as reliable sources of care. The present study is a preliminary psychometric evaluation of a potentially cost-effective method of assessing implicit internal working models of attachment through the development of an Implicit Association Test (IAT). A racially diverse sample of 104 college females was administered Internet-based versions of three IATs (assessing views of the self, mother, and father) as well as self-report measures of attachment and interpersonal problems. Analyses were conducted to evaluate the (a) internal consistency of each task, (b) correlations among the tasks, (c) concurrent validity, and (d) convergent validity. Adequate internal consistency was noted and correlations among the three IATs were significant. No significant associations were observed between the explicit self-report measures of attachment and the IATs. Two primary areas for future research are discussed. First, future research should utilize an implicit attachment measure alongside an IAT. Second, future research should reevaluate the IAT stimuli used.

Exposure to Graphic Warning Labels on Cigarette Packages: Effects on Implicit and Explicit Attitudes toward Smoking among Young Adults

PubMed Central

Macy, Jonathan T.; Chassin, Laurie; Presson, Clark C.; Yeung, Ellen

2015-01-01

Objective Test the effect of exposure to the U.S. Food and Drug Administration’s proposed graphic images with text warning statements for cigarette packages on implicit and explicit attitudes toward smoking. Design and methods A two-session web-based study was conducted with 2192 young adults 18–25 years old. During session one, demographics, smoking behavior, and baseline implicit and explicit attitudes were assessed. Session two, completed on average 18 days later, contained random assignment to viewing one of three sets of cigarette packages, graphic images with text warnings, text warnings only, or current U.S Surgeon General’s text warnings. Participants then completed post-exposure measures of implicit and explicit attitudes. ANCOVAs tested the effect of condition on the outcomes, controlling for baseline attitudes. Results Smokers who viewed packages with graphic images plus text warnings demonstrated more negative implicit attitudes compared to smokers in the other conditions (p=.004). For the entire sample, explicit attitudes were more negative for those who viewed graphic images plus text warnings compared to those who viewed current U.S. Surgeon General’s text warnings (p=.014), but there was no difference compared to those who viewed text-only warnings. Conclusion Graphic health warnings on cigarette packages can influence young adult smokers’ implicit attitudes toward smoking. PMID:26442992

Algorithm development for Maxwell's equations for computational electromagnetism

NASA Technical Reports Server (NTRS)

Goorjian, Peter M.

1990-01-01

A new algorithm has been developed for solving Maxwell's equations for the electromagnetic field. It solves the equations in the time domain with central, finite differences. The time advancement is performed implicitly, using an alternating direction implicit procedure. The space discretization is performed with finite volumes, using curvilinear coordinates with electromagnetic components along those directions. Sample calculations are presented of scattering from a metal pin, a square and a circle to demonstrate the capabilities of the new algorithm.

Reward and punishment learning in daily life: A replication study.

PubMed

Heininga, Vera E; van Roekel, Eeske; Wichers, Marieke; Oldehinkel, Albertine J

2017-01-01

Day-to-day experiences are accompanied by feelings of Positive Affect (PA) and Negative Affect (NA). Implicitly, without conscious processing, individuals learn about the reward and punishment value of each context and activity. These associative learning processes, in turn, affect the probability that individuals will re-engage in such activities or seek out that context. So far, implicit learning processes are almost exclusively investigated in controlled laboratory settings and not in daily life. Here we aimed to replicate the first study that investigated implicit learning processes in real life, by means of the Experience Sampling Method (ESM). That is, using an experience-sampling study with 90 time points (three measurements over 30 days), we prospectively measured time spent in social company and amount of physical activity as well as PA and NA in the daily lives of 18-24-year-old young adults (n = 69 with anhedonia, n = 69 without anhedonia). Multilevel analyses showed a punishment learning effect with regard to time spent in company of friends, but not a reward learning effect. Neither reward nor punishment learning effects were found with regard to physical activity. Our study shows promising results for future research on implicit learning processes in daily life, with the proviso of careful consideration of the timescale used. Short-term retrospective ESM design with beeps approximately six hours apart may suffer from mismatch noise that hampers accurate detection of associative learning effects over time.

From ideal to real: a longitudinal study of the role of implicit leadership theories on leader-member exchanges and employee outcomes.

PubMed

Epitropaki, Olga; Martin, Robin

2005-07-01

The results of the present longitudinal study demonstrate the importance of implicit leadership theories (ILTs) for the quality of leader-member exchanges (LMX) and employees' organizational commitment, job satisfaction, and well-being. Results based on a sample of 439 employees who completed the study questionnaires at 2 time points showed that the closer employees perceived their actual manager's profile to be to the ILTs they endorsed, the better the quality of LMX. Results also indicated that the implicit-explicit leadership traits difference had indirect effects on employee attitudes and well-being. These findings were consistent across employee groups that differed in terms of job demand and the duration of manager-employee relation, but not in terms of motivation. Furthermore, crossed-lagged modeling analyses of the longitudinal data explored the possibility of reciprocal effects between implicit-explicit leadership traits difference and LMX and provided support for the initially hypothesized direction of causal effects. Copyright 2005 APA, all rights reserved.

Continuity from an implicit to an explicit understanding of false belief from infancy to preschool age.

PubMed

Thoermer, Claudia; Sodian, Beate; Vuori, Maria; Perst, Hannah; Kristen, Susanne

2012-03-01

An implicit understanding of false belief indicated by anticipatory looking has been shown to be significantly correlated with performance on explicit false-belief tasks in 3- and 4-year-old children (Low, 2010). Recent evidence from infant research indicates, however, that implicit false-belief understanding guides infants' expectations about goal-directed actions even in the second year of life. The present study presents data from a sample of N= 70 infants who were tested longitudinally at 15, 18, 30, 36 and 48 months with implicit and explicit Theory of Mind measures, as well as an assessment of verbal IQ. Belief-based anticipatory looking in the false-belief task at 18 months significantly predicted verbal false-belief reasoning at 48 months, after controlling for verbal IQ. These findings indicate developmental continuity and conceptual specificity in belief reasoning from infancy to preschool age. They are discussed with respect to competing accounts of infants' understanding of the mind. © 2011 The British Psychological Society.

Testosterone abolishes implicit subordination in social anxiety.

PubMed

Terburg, David; Syal, Supriya; Rosenberger, Lisa A; Heany, Sarah J; Stein, Dan J; Honk, Jack van

2016-10-01

Neuro-evolutionary theories describe social anxiety as habitual subordinate tendencies acquired through a recursive cycle of social defeat and submissive reactions. If so, the steroid hormone testosterone might be of therapeutic value, as testosterone is a main force behind implicit dominance drive in many species including humans. We combined these two theories to investigate whether the tendency to submit to the dominance of others is an implicit mechanism in social anxiety (Study-1), and whether this can be relieved through testosterone administration (Study-2). Using interactive eye-tracking we demonstrate that socially anxious humans more rapidly avert gaze from subliminal angry eye contact (Study-1). We replicate this effect of implicit subordination in social anxiety in an independent sample, which is subsequently completely abolished after a single placebo-controlled sublingual testosterone administration (Study-2). These findings provide crucial evidence for hormonal and behavioral treatment strategies that specifically target mechanisms of dominance and subordination in social anxiety. Copyright © 2016 Elsevier Ltd. All rights reserved.

The implicit rules of combat.

PubMed

Romero, Gorge A; Pham, Michael N; Goetz, Aaron T

2014-12-01

Conspecific violence has been pervasive throughout evolutionary history. The current research tested the hypotheses that individuals implicitly categorize combative contexts (i.e., play fighting, status contests, warfare, and anti-exploitative violence) and use the associated contextual information to guide expectations of combative tactics. Using U.S. and non-U.S. samples, Study 1 demonstrated consistent classification of combative contexts from scenarios for which little information was given and predictable shifts in the acceptability of combative tactics across contexts. Whereas severe tactics (e.g., eye-gouging) were acceptable in warfare and anti-exploitative violence, they were unacceptable in status contests and play fights. These results suggest the existence of implicit rules governing the contexts of combat. In Study 2, we explored the reputational consequences of violating these implicit rules. Results suggest that rule violators (e.g., those who use severe tactics in a status contest) are given less respect. These are the first studies to implicate specialized mechanisms for aggression that use contextual cues of violence to guide expectations and behavior.

Physical Activity Is Associated with Reduced Implicit Learning but Enhanced Relational Memory and Executive Functioning in Young Adults

PubMed Central

Watt, Jennifer C.; Grove, George A.; Wollam, Mariegold E.; Uyar, Fatma; Mataro, Maria; Cohen, Neal J.; Howard, Darlene V.; Howard, James H.; Erickson, Kirk I.

2016-01-01

Accumulating evidence suggests that physical activity improves explicit memory and executive cognitive functioning at the extreme ends of the lifespan (i.e., in older adults and children). However, it is unknown whether these associations hold for younger adults who are considered to be in their cognitive prime, or for implicit cognitive functions that do not depend on motor sequencing. Here we report the results of a study in which we examine the relationship between objectively measured physical activity and (1) explicit relational memory, (2) executive control, and (3) implicit probabilistic sequence learning in a sample of healthy, college-aged adults. The main finding was that physical activity was positively associated with explicit relational memory and executive control (replicating previous research), but negatively associated with implicit learning, particularly in females. These results raise the intriguing possibility that physical activity upregulates some cognitive processes, but downregulates others. Possible implications of this pattern of results for physical health and health habits are discussed. PMID:27584059

Cue-induced activation of implicit affective associations with heroin use in abstinent heroin abusers.

PubMed

Chen, Jianyong; Wang, Xuan; Zhang, Meng; Zhang, Feng; Shen, Mowei

2015-06-01

While drug-related contexts have been shown to influence drug users' implicit and explicit drug-related cognitions, this has been minimally explored in heroin abusers. This study examined the effect of heroin-related cue exposure on implicit and explicit valence and arousal-sedation associations with heroin use for abstinent heroin abusers. In Experiment 1, 39 male abstinent heroin abusers were exposed to heroin-related words and reported cravings before and after cue exposure. They subsequently performed two Extrinsic Affective Simon Tasks (EASTs), which were used to assess implicit valence and arousal-sedation associations with heroin use. Thirty-six male abstinent heroin abusers (controls) only performed the two EASTs. All participants completed measures of explicit expectancy regarding heroin use. In Experiment 2, twenty-eight newly recruited abstinent heroin abusers were exposed to heroin-related pictures, and completed the same implicit and explicit measures used in Experiment 1. A non-significant increase in craving after cue exposure was observed. While participants exposed to heroin-related words or pictures exhibited more positive implicit heroin use associations (relative to negative associations), and such trend was not observed in controls, this difference was not significant across groups. Participants still indicated negative explicit associations with heroin use after cue exposure. Exposure to cues significantly accelerated arousal and sedation responses. Whether cue exposure could change self-reported craving requires further study in abstinent heroin abusers. The exclusively male sample limits generalization of the results. The present findings extend the evidence on whether implicit and explicit heroin-related cognitions are susceptible to context. Copyright © 2014 Elsevier Ltd. All rights reserved.

Implicit and Explicit Self-Esteem Discrepancies, Victimization and the Development of Late Childhood Internalizing Problems.

PubMed

Leeuwis, Franca H; Koot, Hans M; Creemers, Daan H M; van Lier, Pol A C

2015-07-01

Discrepancies between implicit and explicit self-esteem have been linked with internalizing problems among mainly adolescents and adults. Longitudinal research on this association in children is lacking. This study examined the longitudinal link between self-esteem discrepancies and the development of internalizing problems in children. It furthermore examined the possible mediating role of self-esteem discrepancies in the longitudinal link between experiences of peer victimization and internalizing problems development. Children (N = 330, M(age) = 11.2 year; 52.5 % female) were followed over grades five (age 11 years) and six (age 12 years). Self-report measures were used annually to test for victimization and internalizing problems. Implicit self-esteem was assessed using an implicit association test, while explicit self-esteem was assessed via self-reports. Self-esteem discrepancies represented the difference between implicit and explicit self-esteem. Results showed that victimization was associated with increases in damaged self-esteem (higher levels of implicit than explicit self-esteem. Additionally, damaged self-esteem at age 11 years predicted an increase in internalizing problems in children over ages 11 to 12 years. Furthermore, damaged self-esteem mediated the relationship between age 11 years victimization and the development of internalizing problems. No impact of fragile self-esteem (lower levels of implicit than explicit self-esteem) on internalizing problems was found. The results thus underscore that, as found in adolescent and adult samples, damaged self-esteem is a predictor of increases in childhood internalizing problems. Moreover, damaged self-esteem might explain why children who are victimized develop internalizing problems. Implications are discussed.

Implicit associations in social anxiety disorder: the effects of comorbid depression.

PubMed

Wong, Judy; Morrison, Amanda S; Heimberg, Richard G; Goldin, Philippe R; Gross, James J

2014-08-01

Implicit associations of the self to concepts like "calm" have been shown to be weaker in persons with social anxiety than in non-anxious healthy controls. However, other implicit self associations, such as those to acceptance or rejection, have been less studied in social anxiety, and none of this work has been conducted with clinical samples. Furthermore, the importance of depression in these relationships has not been well investigated. We addressed these issues by administering two Implicit Association Tests (IATs; Greenwald, McGhee, & Schwartz, 1998), one examining the implicit association of self/other to anxiety/calmness and the other examining the association of self/other to rejection/acceptance, to individuals with generalized social anxiety disorder (SAD, n=85), individuals with generalized SAD and a current or past diagnosis of major depressive disorder or current dysthymic disorder (n=47), and non-anxious, non-depressed healthy controls (n=44). The SAD and SAD-depression groups showed weaker implicit self-calmness associations than healthy controls, with the comorbid group showing the weakest self-calmness associations. The SAD-depression group showed the weakest implicit self-acceptance associations; no difference was found between non-depressed individuals with SAD and healthy controls. Post hoc analyses revealed that differences appeared to be driven by those with current depression. The SAD-only and SAD-depression groups did not differ in self-reported (explicit) social anxiety. The implications of these findings for the understanding of SAD-depression comorbidity and for the treatment of SAD are considered. Copyright © 2014 Elsevier Ltd. All rights reserved.

Multiparameter flow cytometry of a pH sensitive ligand bound to receptors and inside cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fay, S.P.; Habbersett, R.; Posner, R.G.

1993-01-01

Because fluoresceinated ligands of the neutrophil formyl peptide receptor can be protonated either upon binding to the receptor on the cell surface or in acidified intracellular compartments, the authors synthesized a ligand conjugated to the pH sensitive fluorescent probe SNAFL (CHO-Met-Leu-Phe-Phe-Lys-SNAFL). In the three laser flow cytometer at LANL, protonated dye is excited at 488 nm and emits at 530 nm; unprotonated dye is excited at 568 nm and emits at 650 nm. Detection at the isobestic and isoemissive points at 528 and 600 nm is used to keep track of variations in ligand concentration from sample to sample. Themore » SNAFL-ligand bound to HL-60 cells (which overexpress the formyl peptide receptor) was compared to the free ligand in solution over a pH range from 6.5 to 9.0. The results suggest that the ligand bound to cell surface receptors was protonated in the binding pocket, possibly by virtue of its proximity to His 90, based on sequence data. When the cells were raised from 4[degrees] to 37[degrees], they also observed a time-dependent acidification of the ligand, indicative of ligand-receptor processing beginning 3-4 minutes after internalization.« less

Affinity purification using recombinant PXR as a tool to characterize environmental ligands.

PubMed

Dagnino, Sonia; Bellet, Virginie; Grimaldi, Marina; Riu, Anne; Aït-Aïssa, Sélim; Cavaillès, Vincent; Fenet, Hélène; Balaguer, Patrick

2014-02-01

Many environmental endocrine disrupting compounds act as ligands for nuclear receptors. The human pregnane X receptor (hPXR), for instance, is activated by a variety of environmental ligands such as steroids, pharmaceutical drugs, pesticides, alkylphenols, polychlorinated biphenyls and polybromo diethylethers. Some of us have previously reported the occurrence of hPXR ligands in environmental samples but failed to identify them. The aim of this study was to test whether a PXR-affinity column, in which recombinant hPXR was immobilized on solid support, could help the purification of these chemicals. Using PXR ligands of different affinity (10 nM < EC50 < 10 μM), we demonstrated that the PXR-affinity preferentially column captured ligands with medium to high affinities (EC50 < 1 μM). Furthermore, by using the PXR-affinity column to analyze an environmental sample containing ERα, AhR, AR, and PXR activities, we show that (i) half of the PXR activity of the sample was due to compounds with medium to high affinity for PXR and (ii) PXR shared ligands with ERα, AR, and AhR. These findings demonstrate that the newly developed PXR-affinity column coupled to reporter cell lines represents a valuable tool for the characterization of the nature of PXR active compounds and should therefore guide and facilitate their further analysis. Copyright © 2012 Wiley Periodicals, Inc., a Wiley company.

Structural Diversity of Ligand-Binding Androgen Receptors Revealed by Microsecond Long Molecular Dynamics Simulations and Enhanced Sampling.

PubMed

Duan, Mojie; Liu, Na; Zhou, Wenfang; Li, Dan; Yang, Minghui; Hou, Tingjun

2016-09-13

Androgen receptor (AR) plays important roles in the development of prostate cancer (PCa). The antagonistic drugs, which suppress the activity of AR, are widely used in the treatment of PCa. However, the molecular mechanism of antagonism about how ligands affect the structures of AR remains elusive. To better understand the conformational variability of ARs bound with agonists or antagonists, we performed long time unbiased molecular dynamics (MD) simulations and enhanced sampling simulations for the ligand binding domain of AR (AR-LBD) in complex with various ligands. Based on the simulation results, we proposed an allosteric pathway linking ligands and helix 12 (H12) of AR-LBD, which involves the interactions among the ligands and the residues W741, H874, and I899. The interaction pathway provides an atomistic explanation of how ligands affect the structure of AR-LBD. A repositioning of H12 was observed, but it is facilitated by the C-terminal of H12, instead of by the loop between helix 11 (H11) and H12. The bias-exchange metadynamics simulations further demonstrated the above observations. More importantly, the free energy profiles constructed by the enhanced sampling simulations revealed the transition process between the antagonistic form and agonistic form of AR-LBD. Our results would be helpful for the design of more efficient antagonists of AR to combat PCa.

Large scale affinity calculations of cyclodextrin host-guest complexes: Understanding the role of reorganization in the molecular recognition process

PubMed Central

Wickstrom, Lauren; He, Peng; Gallicchio, Emilio; Levy, Ronald M.

2013-01-01

Host-guest inclusion complexes are useful models for understanding the structural and energetic aspects of molecular recognition. Due to their small size relative to much larger protein-ligand complexes, converged results can be obtained rapidly for these systems thus offering the opportunity to more reliably study fundamental aspects of the thermodynamics of binding. In this work, we have performed a large scale binding affinity survey of 57 β-cyclodextrin (CD) host guest systems using the binding energy distribution analysis method (BEDAM) with implicit solvation (OPLS-AA/AGBNP2). Converged estimates of the standard binding free energies are obtained for these systems by employing techniques such as parallel Hamitionian replica exchange molecular dynamics, conformational reservoirs and multistate free energy estimators. Good agreement with experimental measurements is obtained in terms of both numerical accuracy and affinity rankings. Overall, average effective binding energies reproduce affinity rank ordering better than the calculated binding affinities, even though calculated binding free energies, which account for effects such as conformational strain and entropy loss upon binding, provide lower root mean square errors when compared to measurements. Interestingly, we find that binding free energies are superior rank order predictors for a large subset containing the most flexible guests. The results indicate that, while challenging, accurate modeling of reorganization effects can lead to ligand design models of superior predictive power for rank ordering relative to models based only on ligand-receptor interaction energies. PMID:25147485

Expression of nociceptive ligands in canine osteosarcoma.

PubMed

Shor, S; Fadl-Alla, B A; Pondenis, H C; Zhang, X; Wycislo, K L; Lezmi, S; Fan, T M

2015-01-01

Canine osteosarcoma (OS) is associated with localized pain as a result of tissue injury from tumor infiltration and peritumoral inflammation. Malignant bone pain is caused by stimulation of peripheral pain receptors, termed nociceptors, which reside in the localized tumor microenvironment, including the periosteal and intramedullary bone cavities. Several nociceptive ligands have been determined to participate directly or indirectly in generating bone pain associated with diverse skeletal abnormalities. Canine OS cells actively produce nociceptive ligands with the capacity to directly or indirectly activate peripheral pain receptors residing in the bone tumor microenvironment. Ten dogs with appendicular OS. Expression of nerve growth factor, endothelin-1, and microsomal prostaglandin E synthase-1 was characterized in OS cell lines and naturally occurring OS samples. In 10 dogs with OS, circulating concentrations of nociceptive ligands were quantified and correlated with subjective pain scores and tumor volume in patients treated with standardized palliative therapies. Canine OS cells express and secrete nerve growth factor, endothelin-1, and prostaglandin E2. Naturally occurring OS samples uniformly express nociceptive ligands. In a subset of OS-bearing dogs, circulating nociceptive ligand concentrations were detectable but failed to correlate with pain status. Localized foci of nerve terminal proliferation were identified in a minority of primary bone tumor samples. Canine OS cells express nociceptive ligands, potentially permitting active participation of OS cells in the generation of malignant bone pain. Specific inhibitors of nociceptive ligand signaling pathways might improve pain control in dogs with OS. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of American College of Veterinary Internal Medicine.

Task-related functional connectivity of the caudate mediates the association between trait mindfulness and implicit learning in older adults.

PubMed

Stillman, Chelsea M; You, Xiaozhen; Seaman, Kendra L; Vaidya, Chandan J; Howard, James H; Howard, Darlene V

2016-08-01

Accumulating evidence shows a positive relationship between mindfulness and explicit cognitive functioning, i.e., that which occurs with conscious intent and awareness. However, recent evidence suggests that there may be a negative relationship between mindfulness and implicit types of learning, or those that occur without conscious awareness or intent. Here we examined the neural mechanisms underlying the recently reported negative relationship between dispositional mindfulness and implicit probabilistic sequence learning in both younger and older adults. We tested the hypothesis that the relationship is mediated by communication, or functional connectivity, of brain regions once traditionally considered to be central to dissociable learning systems: the caudate, medial temporal lobe (MTL), and prefrontal cortex (PFC). We first replicated the negative relationship between mindfulness and implicit learning in a sample of healthy older adults (60-90 years old) who completed three event-related runs of an implicit sequence learning task. Then, using a seed-based connectivity approach, we identified task-related connectivity associated with individual differences in both learning and mindfulness. The main finding was that caudate-MTL connectivity (bilaterally) was positively correlated with learning and negatively correlated with mindfulness. Further, the strength of task-related connectivity between these regions mediated the negative relationship between mindfulness and learning. This pattern of results was limited to the older adults. Thus, at least in healthy older adults, the functional communication between two interactive learning-relevant systems can account for the relationship between mindfulness and implicit probabilistic sequence learning.

Implicit Processing of Visual Emotions Is Affected by Sound-Induced Affective States and Individual Affective Traits

PubMed Central

Quarto, Tiziana; Blasi, Giuseppe; Pallesen, Karen Johanne; Bertolino, Alessandro; Brattico, Elvira

2014-01-01

The ability to recognize emotions contained in facial expressions are affected by both affective traits and states and varies widely between individuals. While affective traits are stable in time, affective states can be regulated more rapidly by environmental stimuli, such as music, that indirectly modulate the brain state. Here, we tested whether a relaxing or irritating sound environment affects implicit processing of facial expressions. Moreover, we investigated whether and how individual traits of anxiety and emotional control interact with this process. 32 healthy subjects performed an implicit emotion processing task (presented to subjects as a gender discrimination task) while the sound environment was defined either by a) a therapeutic music sequence (MusiCure), b) a noise sequence or c) silence. Individual changes in mood were sampled before and after the task by a computerized questionnaire. Additionally, emotional control and trait anxiety were assessed in a separate session by paper and pencil questionnaires. Results showed a better mood after the MusiCure condition compared with the other experimental conditions and faster responses to happy faces during MusiCure compared with angry faces during Noise. Moreover, individuals with higher trait anxiety were faster in performing the implicit emotion processing task during MusiCure compared with Silence. These findings suggest that sound-induced affective states are associated with differential responses to angry and happy emotional faces at an implicit stage of processing, and that a relaxing sound environment facilitates the implicit emotional processing in anxious individuals. PMID:25072162

Toward a Comprehensive Understanding of Executive Cognitive Function in Implicit Racial Bias

PubMed Central

Ito, Tiffany A.; Friedman, Naomi P.; Bartholow, Bruce D.; Correll, Joshua; Loersch, Chris; Altamirano, Lee J.; Miyake, Akira

2014-01-01

Although performance on laboratory-based implicit bias tasks often is interpreted strictly in terms of the strength of automatic associations, recent evidence suggests that such tasks are influenced by higher-order cognitive control processes, so-called executive functions (EFs). However, extant work in this area has been limited by failure to account for the unity and diversity of EFs, focus on only a single measure of bias and/or EF, and relatively small sample sizes. The current study sought to comprehensively model the relation between individual differences in EFs and the expression of racial bias in three commonly used laboratory measures. Participants (N=485) completed a battery of EF tasks (session 1) and three racial bias tasks (session 2), along with numerous individual difference questionnaires. The main findings were as follows: (1) measures of implicit bias were only weakly intercorrelated; (2) EF and estimates of automatic processes both predicted implicit bias and also interacted, such that the relation between automatic processes and bias expression was reduced at higher levels of EF; (3) specific facets of EF were differentially associated with overall task performance and controlled processing estimates across different bias tasks; (4) EF did not moderate associations between implicit and explicit measures of bias; and (5) external, but not internal, motivation to control prejudice depended on EF to reduce bias expression. Findings are discussed in terms of the importance of global and specific EF abilities in determining expression of implicit racial bias. PMID:25603372

An exploration of Intolerance of Uncertainty and memory bias.

PubMed

Francis, Kylie; Dugas, Michel J; Ricard, Nathalie C

2016-09-01

Research suggests that individuals high in Intolerance of Uncertainty (IU) have information processing biases, which may explain the close relationship between IU and worry. Specifically, high IU individuals show an attentional bias for uncertainty, and negatively interpret uncertain information. However, evidence of a memory bias for uncertainty among high IU individuals is limited. This study therefore explored the relationship between IU and memory for uncertainty. In two separate studies, explicit and implicit memory for uncertain compared to other types of words was assessed. Cognitive avoidance and other factors that could influence information processing were also examined. IUS Factor 1 was a significant positive predictor of explicit memory for positive words, and IUS Factor 2 a significant negative predictor of implicit memory for positive words. Stimulus relevance and vocabulary were significant predictors of implicit memory for uncertain words. Cognitive avoidance was a significant predictor of both explicit and implicit memory for threat words. Female gender was a significant predictor of implicit memory for uncertain and neutral words. Word stimuli such as those used in these studies may not be the optimal way of assessing information processing biases related to IU. In addition, the predominantly female, largely student sample may limit the generalizability of the findings. Future research focusing on IU factors, stimulus relevance, and both explicit and implicit memory, was recommended. The potential role of cognitive avoidance on memory, information processing, and worry was explored. Copyright © 2016 Elsevier Ltd. All rights reserved.

Diagnostic Sampling to Reveal Hidden Lead and Copper Health Risks

EPA Science Inventory

Lead, copper and other metallic contamination sources in premise drinking water plumbing systems, are unevenly distributed and are usually hidden from thought, view, or both. Many sampling protocols exist, each with some set of implicit assumptions governing its applicability to...

The Effects of Eliciting Implicit versus Explicit Social Support among Youths Susceptible for Late-Onset Smoking

PubMed Central

Roberts, Megan E.; Bernstein, Michael H.; Colby, Suzanne M.

2016-01-01

Purpose Adolescents susceptible to late-onset smoking (becoming regular smokers at age 18 or later) are an understudied population. Social support is a promising target for intervention, but it is important to distinguish between implicit social support (reminders that one belongs to a network of valued others) and explicit social support (seeking and receiving advice and emotional solace). This study aimed to test the potential protective influence of implicit and explicit social support on reducing the risk of late-onset smoking. Methods Fifty-eight smoking-susceptible youths (aged 16–18, 45% African American, 55% non-Hispanic White) completed an experimental session that included a video-recording task designed to elicit thoughts about implicit, explicit, or no social support. Youths reported their behavioral willingness and intentions (BW and BI) to smoke immediately following the social support manipulation; a random sample of 39 youths reported again at a 3-week follow-up. Results Following the manipulation, BW and BI for cigarette smoking were significantly higher among youths assigned to the explicit-support condition, compared to those in the implicit-support or control conditions. At follow-up, BW and BI were highest in the explicit-support condition and lowest in the implicit-support condition, but the differences were not significant. Conclusions Overall, findings indicated that for teens susceptible for late-onset smoking, eliciting thoughts about implicit social support produces lower risk for cigarette initiation than does eliciting thoughts about explicit social support. The present results and the video task that yielded them are important to researchers and practitioners interested in reducing the likelihood of late-onset smoking. PMID:27322670

Brain response to masked and unmasked facial emotions as a function of implicit and explicit personality self-concept of extraversion.

PubMed

Suslow, Thomas; Kugel, Harald; Lindner, Christian; Dannlowski, Udo; Egloff, Boris

2017-01-06

Extraversion-introversion is a personality dimension referring to individual differences in social behavior. In the past, neurobiological research on extraversion was almost entirely based upon questionnaires which inform about the explicit self-concept. Today, indirect measures are available that tap into the implicit self-concept of extraversion which is assumed to result from automatic processing functions. In our study, brain activation while viewing facial expression of affiliation relevant (i.e., happiness, and disgust) and irrelevant (i.e., fear) emotions was examined as a function of the implicit and explicit self-concept of extraversion and processing mode (automatic vs. controlled). 40 healthy volunteers watched blocks of masked and unmasked emotional faces while undergoing functional magnetic resonance imaging. The Implicit Association Test and the NEO Five-Factor Inventory were applied as implicit and explicit measures of extraversion which were uncorrelated in our sample. Implicit extraversion was found to be positively associated with neural response to masked happy faces in the thalamus and temporo-parietal regions and to masked disgust faces in cerebellar areas. Moreover, it was positively correlated with brain response to unmasked disgust faces in the amygdala and cortical areas. Explicit extraversion was not related to brain response to facial emotions when controlling trait anxiety. The implicit compared to the explicit self-concept of extraversion seems to be more strongly associated with brain activation not only during automatic but also during controlled processing of affiliation relevant facial emotions. Enhanced neural response to facial disgust could reflect high sensitivity to signals of interpersonal rejection in extraverts (i.e., individuals with affiliative tendencies). Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

The effects of eliciting implicit versus explicit social support among youths susceptible for late-onset smoking.

PubMed

Roberts, Megan E; Bernstein, Michael H; Colby, Suzanne M

2016-11-01

Adolescents susceptible to late-onset smoking (becoming regular smokers at age 18 or later) are an understudied population. Social support is a promising target for intervention, but it is important to distinguish between implicit social support (reminders that one belongs to a network of valued others) and explicit social support (seeking and receiving advice and emotional solace). This study aimed to test the potential protective influence of implicit and explicit social support on reducing the risk of late-onset smoking. Fifty-eight smoking-susceptible youths (aged 16-18, 45% African American, 55% non-Hispanic White) completed an experimental session that included a video-recording task designed to elicit thoughts about implicit, explicit, or no social support. Youths reported their behavioral willingness and intentions (BW and BI) to smoke immediately following the social support manipulation; a random sample of 39 youths reported again at a 3-week follow-up. Following the manipulation, BW and BI for cigarette smoking were significantly higher among youths assigned to the explicit-support condition, compared to those in the implicit-support or control conditions. At follow-up, BW and BI were highest in the explicit-support condition and lowest in the implicit-support condition, but the differences were not significant. Overall, findings indicated that for teens susceptible for late-onset smoking, eliciting thoughts about implicit social support produces lower risk for cigarette initiation than does eliciting thoughts about explicit social support. The present results and the video task that yielded them are important to researchers and practitioners interested in reducing the likelihood of late-onset smoking. Copyright © 2016 Elsevier Ltd. All rights reserved.

Testing the cognitive catalyst model of rumination with explicit and implicit cognitive content.

PubMed

Sova, Christopher C; Roberts, John E

2018-06-01

The cognitive catalyst model posits that rumination and negative cognitive content, such as negative schema, interact to predict depressive affect. Past research has found support for this model using explicit measures of negative cognitive content such as self-report measures of trait self-esteem and dysfunctional attitudes. The present study tested whether these findings would extend to implicit measures of negative cognitive content such as implicit self-esteem, and whether effects would depend on initial mood state and history of depression. Sixty-one undergraduate students selected on the basis of depression history (27 previously depressed; 34 never depressed) completed explicit and implicit measures of negative cognitive content prior to random assignment to a rumination induction followed by a distraction induction or vice versa. Dysphoric affect was measured both before and after these inductions. Analyses revealed that explicit measures, but not implicit measures, interacted with rumination to predict change in dysphoric affect, and these interactions were further moderated by baseline levels of dysphoria. Limitations include the small nonclinical sample and use of a self-report measure of depression history. These findings suggest that rumination amplifies the association between explicit negative cognitive content and depressive affect primarily among people who are already experiencing sad mood. Copyright © 2018 Elsevier Ltd. All rights reserved.

Drinking without thinking: an implicit measure of alcohol motivation predicts failure to control alcohol use.

PubMed

Ostafin, Brian D; Marlatt, G Alan; Greenwald, Anthony G

2008-11-01

Addiction is characterized by dyscontrol - substance use despite intentions to restrain. Using a sample of at-risk drinkers, the present study examined whether an implicit measure of alcohol motivation (the Implicit Association Test [IAT]; Greenwald, A.G., McGhee, D.E., & Schwartz, J.L.K. (1998). Measuring individual differences in implicit cognition: the Implicit Association Test. Journal of Personality and Social Psychology, 74, 1464-1480) would predict dyscontrol of alcohol use. Participants completed an IAT and, to elicit motivation to restrain alcohol use, were instructed that greater consumption in a taste test would impair performance on a later task for which they could win a prize. All participants viewed aversive slides and then completed a thought-listing task. Participants either exerted self-control by suppressing negative affect and thoughts regarding the slides or did not exert self-control. Post-manipulation, the groups did not differ in mood, urge to drink or motivation to restrain consumption. During the subsequent taste test, participants whose self-control resources were depleted consumed more alcohol than did those in the control group. Additionally, the IAT, but not an explicit measure of alcohol motivation, more strongly predicted alcohol use when self-control resources were depleted. The results indicate that the IAT may have utility in predicting dyscontrolled alcohol use.

Promoting health (implicitly)? A longitudinal content analysis of implicit health information in cigarette advertising, 1954-2003.

PubMed

Paek, Hye-Jin; Reid, Leonard N; Choi, Hojoon; Jeong, Hyun Ju

2010-10-01

Tobacco studies indicate that health-related information in cigarette advertising leads consumers to underestimate the detrimental health effects of smoking and contributes to their smoking-related perceptions, beliefs, and attitudes. This study examined the frequencies and kinds of implicit health information in cigarette advertising across five distinct smoking eras covering the years 1954-2003. Analysis of 1,135 cigarette advertisements collected through multistage probability sampling of three popular consumer magazines found that the level of implicit health information (i.e., "light" cigarette, cigarette pack color, verbal and visual health cues, cigarette portrayals, and human model-cigarette interaction) in post-Master Settlement Agreement [MSA] era ads is similar to the level in ads from early smoking eras. Specifically, "light" cigarettes were frequently promoted, and presence of light colors in cigarette packs seemed dominant after the probroadcast ban era. Impressionistic verbal health cues (e.g., soft, mild, and refreshing) appeared more frequently in post-MSA era ads than in pre-MSA era ads. Most notably, a majority of the cigarette ads portrayed models smoking, lighting, or offering a cigarette to others. The potential impact of implicit health information is discussed in the contexts of social cognition and Social Cognitive Theory. Policy implications regarding our findings are also detailed.

Implicit bias among physicians and its prediction of thrombolysis decisions for black and white patients.

PubMed

Green, Alexander R; Carney, Dana R; Pallin, Daniel J; Ngo, Long H; Raymond, Kristal L; Iezzoni, Lisa I; Banaji, Mahzarin R

2007-09-01

Studies documenting racial/ethnic disparities in health care frequently implicate physicians' unconscious biases. No study to date has measured physicians' unconscious racial bias to test whether this predicts physicians' clinical decisions. To test whether physicians show implicit race bias and whether the magnitude of such bias predicts thrombolysis recommendations for black and white patients with acute coronary syndromes. An internet-based tool comprising a clinical vignette of a patient presenting to the emergency department with an acute coronary syndrome, followed by a questionnaire and three Implicit Association Tests (IATs). Study invitations were e-mailed to all internal medicine and emergency medicine residents at four academic medical centers in Atlanta and Boston; 287 completed the study, met inclusion criteria, and were randomized to either a black or white vignette patient. IAT scores (normal continuous variable) measuring physicians' implicit race preference and perceptions of cooperativeness. Physicians' attribution of symptoms to coronary artery disease for vignette patients with randomly assigned race, and their decisions about thrombolysis. Assessment of physicians' explicit racial biases by questionnaire. Physicians reported no explicit preference for white versus black patients or differences in perceived cooperativeness. In contrast, IATs revealed implicit preference favoring white Americans (mean IAT score = 0.36, P < .001, one-sample t test) and implicit stereotypes of black Americans as less cooperative with medical procedures (mean IAT score 0.22, P < .001), and less cooperative generally (mean IAT score 0.30, P < .001). As physicians' prowhite implicit bias increased, so did their likelihood of treating white patients and not treating black patients with thrombolysis (P = .009). This study represents the first evidence of unconscious (implicit) race bias among physicians, its dissociation from conscious (explicit) bias, and its predictive validity. Results suggest that physicians' unconscious biases may contribute to racial/ethnic disparities in use of medical procedures such as thrombolysis for myocardial infarction.

Identifying Marine Copper-Binding Ligands in Seawater

NASA Astrophysics Data System (ADS)

Whitby, H.; Hollibaugh, J. T.; Maldonado, M. T.; Ouchi, S.; van den Berg, S. M.

2016-02-01

Complexation reactions are important because they affect the bioavailability of trace metals such as copper and iron. For example, organic complexation can determine whether copper is a limiting or a toxic micronutrient at natural levels. Copper competes with iron for complexing ligands, and when iron is limiting, copper can also substitute for iron in some metabolic pathways. The speciation of copper can be measured using complexing capacity titrations, which provide the concentration of individual ligand classes (L1, L2 etc.) and the complex stabilities (log K). Using methods recently developed in our laboratory, we show that the ligands within these classes can be measured independently of titrations, thus confirming the titration method and simultaneously identifying the ligands within each class. Thiols were identified as the L1 ligand class and humic compounds as the weaker L2 class in samples from coastal Georgia, USA, collected monthly from April to December. Log K values of the ligand complexes were consistent with values expected for thiols and humic substances. Recent results from culture studies and from samples collected along Line P, a coastal - oceanic transect in the HNLC region of the NE subarctic Pacific, will be presented in comparison to the estuarine results. This comparison will help to broaden our perspective on copper complexation and the ligands responsible, furthering our understanding of ligand sources and life cycles.

Reward and punishment learning in daily life: A replication study

PubMed Central

van Roekel, Eeske; Wichers, Marieke; Oldehinkel, Albertine J.

2017-01-01

Day-to-day experiences are accompanied by feelings of Positive Affect (PA) and Negative Affect (NA). Implicitly, without conscious processing, individuals learn about the reward and punishment value of each context and activity. These associative learning processes, in turn, affect the probability that individuals will re-engage in such activities or seek out that context. So far, implicit learning processes are almost exclusively investigated in controlled laboratory settings and not in daily life. Here we aimed to replicate the first study that investigated implicit learning processes in real life, by means of the Experience Sampling Method (ESM). That is, using an experience-sampling study with 90 time points (three measurements over 30 days), we prospectively measured time spent in social company and amount of physical activity as well as PA and NA in the daily lives of 18-24-year-old young adults (n = 69 with anhedonia, n = 69 without anhedonia). Multilevel analyses showed a punishment learning effect with regard to time spent in company of friends, but not a reward learning effect. Neither reward nor punishment learning effects were found with regard to physical activity. Our study shows promising results for future research on implicit learning processes in daily life, with the proviso of careful consideration of the timescale used. Short-term retrospective ESM design with beeps approximately six hours apart may suffer from mismatch noise that hampers accurate detection of associative learning effects over time. PMID:28976985

Coupled protein-ligand dynamics in truncated hemoglobin N from atomistic simulations and transition networks.

PubMed

Cazade, Pierre-André; Berezovska, Ganna; Meuwly, Markus

2015-05-01

The nature of ligand motion in proteins is difficult to characterize directly using experiment. Specifically, it is unclear to what degree these motions are coupled. All-atom simulations are used to sample ligand motion in truncated Hemoglobin N. A transition network analysis including ligand- and protein-degrees of freedom is used to analyze the microscopic dynamics. Clustering of two different subsets of MD trajectories highlights the importance of a diverse and exhaustive description to define the macrostates for a ligand-migration network. Monte Carlo simulations on the transition matrices from one particular clustering are able to faithfully capture the atomistic simulations. Contrary to clustering by ligand positions only, including a protein degree of freedom yields considerably improved coarse grained dynamics. Analysis with and without imposing detailed balance agree closely which suggests that the underlying atomistic simulations are converged with respect to sampling transitions between neighboring sites. Protein and ligand dynamics are not independent from each other and ligand migration through globular proteins is not passive diffusion. Transition network analysis is a powerful tool to analyze and characterize the microscopic dynamics in complex systems. This article is part of a Special Issue entitled Recent developments of molecular dynamics. Copyright © 2014 Elsevier B.V. All rights reserved.

Planar optical waveguide based sandwich assay sensors and processes for the detection of biological targets including early detection of cancers

DOEpatents

Martinez, Jennifer S [Santa Fe, NM; Swanson, Basil I [Los Alamos, NM; Shively, John E [Arcadia, CA; Li, Lin [Monrovia, CA

2009-06-02

An assay element is described including recognition ligands adapted for binding to carcinoembryonic antigen (CEA) bound to a film on a single mode planar optical waveguide, the film from the group of a membrane, a polymerized bilayer membrane, and a self-assembled monolayer containing polyethylene glycol or polypropylene glycol groups therein and an assay process for detecting the presence of CEA is described including injecting a possible CEA-containing sample into a sensor cell including the assay element, maintaining the sample within the sensor cell for time sufficient for binding to occur between CEA present within the sample and the recognition ligands, injecting a solution including a reporter ligand into the sensor cell; and, interrogating the sample within the sensor cell with excitation light from the waveguide, the excitation light provided by an evanescent field of the single mode penetrating into the biological target-containing sample to a distance of less than about 200 nanometers from the waveguide thereby exciting any bound reporter ligand within a distance of less than about 200 nanometers from the waveguide and resulting in a detectable signal.

How maltose influences structural changes to bind to maltose-binding protein: results from umbrella sampling simulation.

PubMed

Mascarenhas, Nahren Manuel; Kästner, Johannes

2013-02-01

A well-studied periplasmic-binding protein involved in the abstraction of maltose is maltose-binding protein (MBP), which undergoes a ligand-induced conformational transition from an open (ligand-free) to a closed (ligand-bound) state. Umbrella sampling simulations have been us to estimate the free energy of binding of maltose to MBP and to trace the potential of mean force of the unbinding event using the center-of-mass distance between the protein and ligand as the reaction coordinate. The free energy thus obtained compares nicely with the experimentally measured value justifying our theoretical basis. Measurement of the domain angle (N-terminal-domain - hinge - C-terminal-domain) along the unbinding pathway established the existence of three different states. Starting from a closed state, the protein shifts to an open conformation during the initial unbinding event of the ligand then resides in a semi-open conformation and later resides predominantly in an open-state. These transitions along the ligand unbinding pathway have been captured in greater depth using principal component analysis. It is proposed that in mixed-model, both conformational selection and an induced-fit mechanism combine to the ligand recognition process in MBP. Copyright © 2012 Wiley Periodicals, Inc.

Affective decision-making moderates the effects of automatic associations on alcohol use among drug offenders.

PubMed

Cappelli, Christopher; Ames, Susan; Shono, Yusuke; Dust, Mark; Stacy, Alan

2017-09-01

This study used a dual-process model of cognition in order to investigate the possible influence of automatic and deliberative processes on lifetime alcohol use in a sample of drug offenders. The objective was to determine if automatic/implicit associations in memory can exert an influence over an individual's alcohol use and if decision-making ability could potentially modify the influence of these associations. 168 participants completed a battery of cognitive tests measuring implicit alcohol associations in memory (verb generation) as well as their affective decision-making ability (Iowa Gambling Task). Structural equation modeling procedures were used to test the relationship between implicit associations, decision-making, and lifetime alcohol use. Results revealed that among participants with lower levels of decision-making, implicit alcohol associations more strongly predicted higher lifetime alcohol use. These findings provide further support for the interaction between a specific decision function and its influence over automatic processes in regulating alcohol use behavior in a risky population. Understanding the interaction between automatic associations and decision processes may aid in developing more effective intervention components.

How robust is the IAT? Measuring and manipulating implicit attitudes of East- and West-Germans.

PubMed

Kühnen, U; Schiessl, M; Bauer, N; Paulig, N; Pöhlmann, C; Schmidthals, K

2001-01-01

We investigated consequences of priming East-West-German related self-knowledge for the strength of implicit, ingroup-directed positive evaluations among East- and West-Germans. Based on previous studies we predicted opposite effects of self-knowledge priming for East- and West-Germans. Since in general the East-German stereotype is regarded as more negative than the West-German one, bringing to mind East-West-related self-knowledge (relative to neutral priming) was expected to attenuate ingroup favoritism for East-Germans, but to increase it for West-Germans. After having fulfilled the priming tasks, participants worked on an IAT-version in which the to be classified stimuli were East- or West-German city names (dimension 1) and positive or negative adjectives (dimension 2). Results of Experiment 1 showed (a) that East- and West-German students implicitly evaluated their ingroups as more positive than the outgroups and (b) confirmed the predictions of the priming influence. Experiment 2 replicated these findings with more representative samples from East- and West-Germany. The results are discussed with regard to underlying processes of implicit attitudes in intergroup contexts.

Application of a lower-upper implicit scheme and an interactive grid generation for turbomachinery flow field simulations

NASA Technical Reports Server (NTRS)

Choo, Yung K.; Soh, Woo-Yung; Yoon, Seokkwan

1989-01-01

A finite-volume lower-upper (LU) implicit scheme is used to simulate an inviscid flow in a tubine cascade. This approximate factorization scheme requires only the inversion of sparse lower and upper triangular matrices, which can be done efficiently without extensive storage. As an implicit scheme it allows a large time step to reach the steady state. An interactive grid generation program (TURBO), which is being developed, is used to generate grids. This program uses the control point form of algebraic grid generation which uses a sparse collection of control points from which the shape and position of coordinate curves can be adjusted. A distinct advantage of TURBO compared with other grid generation programs is that it allows the easy change of local mesh structure without affecting the grid outside the domain of independence. Sample grids are generated by TURBO for a compressor rotor blade and a turbine cascade. The turbine cascade flow is simulated by using the LU implicit scheme on the grid generated by TURBO.

Mass spectrometry-based monitoring of millisecond protein–ligand binding dynamics using an automated microfluidic platform

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cong, Yongzheng; Katipamula, Shanta; Trader, Cameron D.

2016-01-01

Characterizing protein-ligand binding dynamics is crucial for understanding protein function and developing new therapeutic agents. We have developed a novel microfluidic platform that features rapid mixing of protein and ligand solutions, variable incubation times, and on-chip electrospray ionization to perform label-free, solution-based monitoring of protein-ligand binding dynamics. This platform offers many advantages including automated processing, rapid mixing, and low sample consumption.

Discrepancies between implicit and explicit motivation and unhealthy eating behavior.

PubMed

Job, Veronika; Oertig, Daniela; Brandstätter, Veronika; Allemand, Mathias

2010-08-01

Many people change their eating behavior as a consequence of stress. One source of stress is intrapersonal psychological conflict as caused by discrepancies between implicit and explicit motives. In the present research, we examined whether eating behavior is related to this form of stress. Study 1 (N=53), a quasi-experimental study in the lab, showed that the interaction between the implicit achievement motive disposition and explicit commitment toward an achievement task significantly predicts the number of snacks consumed in a consecutive taste test. In cross-sectional Study 2 (N=100), with a sample of middle-aged women, overall motive discrepancy was significantly related to diverse indices of unsettled eating. Regression analyses revealed interaction effects specifically for power and achievement motivation and not for affiliation. Emotional distress further partially mediated the relationship between the overall motive discrepancy and eating behavior.

Toward a comprehensive understanding of executive cognitive function in implicit racial bias.

PubMed

Ito, Tiffany A; Friedman, Naomi P; Bartholow, Bruce D; Correll, Joshua; Loersch, Chris; Altamirano, Lee J; Miyake, Akira

2015-02-01

Although performance on laboratory-based implicit bias tasks often is interpreted strictly in terms of the strength of automatic associations, recent evidence suggests that such tasks are influenced by higher-order cognitive control processes, so-called executive functions (EFs). However, extant work in this area has been limited by failure to account for the unity and diversity of EFs, focus on only a single measure of bias and/or EF, and relatively small sample sizes. The current study sought to comprehensively model the relation between individual differences in EFs and the expression of racial bias in 3 commonly used laboratory measures. Participants (N = 485) completed a battery of EF tasks (Session 1) and 3 racial bias tasks (Session 2), along with numerous individual difference questionnaires. The main findings were as follows: (a) measures of implicit bias were only weakly intercorrelated; (b) EF and estimates of automatic processes both predicted implicit bias and also interacted, such that the relation between automatic processes and bias expression was reduced at higher levels of EF; (c) specific facets of EF were differentially associated with overall task performance and controlled processing estimates across different bias tasks; (d) EF did not moderate associations between implicit and explicit measures of bias; and (e) external, but not internal, motivation to control prejudice depended on EF to reduce bias expression. Findings are discussed in terms of the importance of global and specific EF abilities in determining expression of implicit racial bias. PsycINFO Database Record (c) 2015 APA, all rights reserved.

Discrepancies between implicit and explicit self-esteem among adolescents with social anxiety disorder.

PubMed

Schreiber, Franziska; Bohn, Christiane; Aderka, Idan M; Stangier, Ulrich; Steil, Regina

2012-12-01

Previous studies have found high implicit self-esteem (ISE) to prevail concurrently with low explicit self-esteem (ESE) in socially anxious adults. This suggests that self-esteem discrepancies are associated with social anxiety disorder (SAD). Given that the onset of SAD often occurs in adolescence, we investigated self-esteem discrepancies between ISE and ESE in adolescents suffering from SAD. Two implicit measures (Affect Misattribution Procedure, Implicit Association Test) were used both before and after a social threat activation in 20 adolescents with SAD (14-20 years), and compared to 20 healthy adolescents who were matched for age and gender. The Rosenberg Self-Esteem Scale, the Social Cognitions Questionnaire and Beck Depression Inventory were administered as explicit measures. We expected discrepant self-esteem (high ISE, low ESE) in adolescents with SAD, in comparison to congruent self-esteem (positive ISE, positive ESE) in healthy controls, after social threat activation. Both the patient and control groups exhibited high positive ISE on both implicit measures, before as well as after social threat induction. Explicitly, patients suffering from SAD revealed lower levels of ESE, compared to the healthy adolescents. This study is the first to examine ISE and ESE in a clinical sample of adolescent patients with SAD. Our results suggest that SAD is associated with a discrepancy between high ISE and low ESE, after a social-threat manipulation. The findings are discussed in relation to other studies using implicit measures in SAD and may provide a more comprehensive understanding of the role of self-esteem in adolescent SAD. Copyright © 2012 Elsevier Ltd. All rights reserved.

Implicit and explicit self-esteem and their reciprocal relationship with symptoms of depression and social anxiety: a longitudinal study in adolescents.

PubMed

van Tuijl, Lonneke A; de Jong, Peter J; Sportel, B Esther; de Hullu, Eva; Nauta, Maaike H

2014-03-01

A negative self-view is a prominent factor in most cognitive vulnerability models of depression and anxiety. Recently, there has been increased attention to differentiate between the implicit (automatic) and the explicit (reflective) processing of self-related evaluations. This longitudinal study aimed to test the association between implicit and explicit self-esteem and symptoms of adolescent depression and social anxiety disorder. Two complementary models were tested: the vulnerability model and the scarring effect model. Participants were 1641 first and second year pupils of secondary schools in the Netherlands. The Rosenberg Self-Esteem Scale, self-esteem Implicit Association Test and Revised Child Anxiety and Depression Scale were completed to measure explicit self-esteem, implicit self-esteem and symptoms of social anxiety disorder (SAD) and major depressive disorder (MDD), respectively, at baseline and two-year follow-up. Explicit self-esteem at baseline was associated with symptoms of MDD and SAD at follow-up. Symptomatology at baseline was not associated with explicit self-esteem at follow-up. Implicit self-esteem was not associated with symptoms of MDD or SAD in either direction. We relied on self-report measures of MDD and SAD symptomatology. Also, findings are based on a non-clinical sample. Our findings support the vulnerability model, and not the scarring effect model. The implications of these findings suggest support of an explicit self-esteem intervention to prevent increases in MDD and SAD symptomatology in non-clinical adolescents. Copyright © 2013 Elsevier Ltd. All rights reserved.

TASK-RELATED FUNCTIONAL CONNECTIVITY OF THE CAUDATE MEDIATES THE ASSOCIATION BETWEEN TRAIT MINDFULNESS AND IMPLICIT LEARNING IN OLDER ADULTS

PubMed Central

Stillman, Chelsea M.; You, Xiaozhen; Seaman, Kendra L.; Vaidya, Chandan J.; Howard, James H.; Howard, Darlene V.

2016-01-01

Accumulating evidence shows a positive relationship between mindfulness and explicit cognitive functioning, i.e., that which occurs with conscious intent and awareness. However, recent evidence suggests that there may be a negative relationship between mindfulness and implicit types of learning, or those that occur without conscious awareness or intent. Here we examined the neural mechanisms underlying the recently reported negative relationship between dispositional mindfulness and implicit probabilistic sequence learning in both younger and older adults. We tested the hypothesis that the relationship is mediated by communication, or functional connectivity, of brain regions once traditionally considered to be central to dissociable learning systems: the caudate, medial temporal lobe (MTL), and prefrontal cortex (PFC). We first replicated the negative relationship between mindfulness and implicit learning in a sample of healthy older adults (60–90 years old) who completed three event-related runs of an implicit sequence learning task. Then, using a seed-based connectivity approach, we identified task-related connectivity associated with individual differences in both learning and mindfulness. The main finding was that caudate-MTL connectivity (bilaterally) was positively correlated with learning and negatively correlated with mindfulness. Further, the strength of task-related connectivity between these regions mediated the negative relationship between mindfulness and learning. This pattern of results was limited to the older adults. Thus, at least in healthy older adults, the functional communication between two interactive learning-relevant systems can account for the relationship between mindfulness and implicit probabilistic sequence learning. PMID:27121302

A critical role of the human hippocampus in an electrophysiological measure of implicit memory

PubMed Central

Addante, Richard James

2015-01-01

The hippocampus has traditionally been thought to be critical for conscious explicit memory but not necessary for unconscious implicit memory processing. In a recent study of a group of mild amnesia patients with evidence of MTL damage limited to the hippocampus, subjects were tested on a direct test of item recognition confidence while electroencephalogram (EEG) was acquired, and revealed intact measures of explicit memory from 400–600ms (mid-frontal old-new effect, FN400). The current investigation re-analyzed this data to study event-related potentials (ERPs) of implicit memory, using a recently developed procedure that eliminated declarative memory differences. Prior ERP findings from this technique were first replicated in two independent matched control groups, which exhibited reliable implicit memory effects in posterior scalp regions from 400–600 msec, which were topographically dissociated from the explicit memory effects of familiarity. However, patients were found to be dramatically impaired in implicit memory effects relative to control subjects, as quantified by a reliable condition × group interaction. Several control analysis were conducted to consider alternative factors that could account for the results, including outliers, sample size, age, or contamination by explicit memory, and each of these factors were systematically ruled out. Results suggest that the hippocampus plays a fundamental role in aspects of memory processing that is beyond conscious awareness. The current findings therefore indicate that both memory systems of implicit and explicit memory may rely upon the same neural structures – but function in different physiological ways. PMID:25562828

Associations Between Childhood Abuse, Posttraumatic Stress Disorder, and Implicit Emotion Regulation Deficits: Evidence From a Low-Income, Inner-City Population.

PubMed

Powers, Abigail; Etkin, Amit; Gyurak, Anett; Bradley, Bekh; Jovanovic, Tanja

2015-01-01

Childhood abuse is associated with a wide range of negative outcomes, including increased risk for development of emotion dysregulation and psychopathology, such as posttraumatic stress disorder (PTSD). The goal of the present study was to examine associations between child abuse, PTSD symptoms, and performance on an emotional conflict regulation task that assesses implicit emotion regulation abilities. The sample consisted of 67 (94% African American) females recruited from a public, urban hospital. Childhood abuse was measured using the Childhood Trauma Questionnaire, and PTSD was measured using the modified PTSD Symptom Scale. Task accuracy and implicit emotion regulation were measured through an emotional conflict regulation behavioral task. A multivariate analysis of covariance showed that exposure to moderate to severe childhood abuse was significantly related to worse emotional conflict regulation scores independent of current PTSD symptoms, depressive symptoms, and adult trauma exposure, suggesting a deficit in implicit emotion regulation. We also found an interaction between PTSD symptoms and abuse exposure in predicting accuracy on the behavioral task; high levels of PTSD symptoms were associated with poorer task accuracy among individuals who reported moderate to severe exposure to childhood abuse. However, no relationship between implicit emotion regulation abilities and overall PTSD symptom severity was found. This study provides preliminary evidence of an implicit emotion regulation deficit for individuals exposed to significant childhood abuse and further supports the growing evidence that addressing various aspects of emotion dysregulation, such as awareness of emotions and strategies to manage strong emotions, in the context of treatment would be valuable.

Copper-complexing ligands produced by an intact estuarine microbial community in response to copper stress.

NASA Astrophysics Data System (ADS)

Bingham, J.; Dryden, C.; Gordon, A.

2002-12-01

Copper is both an important nutrient and a pollutant in the marine environment. By studying the interactions between microorganisms and copper in the Elizabeth River (VA), home to a major Naval Base, we field tested the hypothesis that picoplankton and/or bacterioplankton produce strong, copper-complexing ligands in response to elevated copper concentrations. A simple light/ dark test was used to distinguish between heterotrophic and phototrophic ligand production. Samples were bottled and moored, submerged one meter, for a week. Direct counts using DAPI stain and epiflourescence were conducted to find concentrations of picoplankton and bacterioplankton. Using cathodic stripping voltammetry, we found the total copper concentrations, and then from a titration of the ligands by copper, the ligand concentrations and conditional stability constants were obtained. The Elizabeth River naturally had between 10-20 nM total dissolved copper concentrations. However when copper complexation was considered we found that the levels of bio-available Cu(II) ions were much lower. In fact in the natural samples the levels were not high enough to affect the relative reproductive rates of several microorganisms. Naturally there was a 50 nM "buffer zone" of ligand to total dissolved copper concentration. Furthermore, when stressed with excess copper, healthy picoplankton produced enough ligand to alleviate toxicity, and rebuild the buffer zone. However bacterioplankton only produced enough ligand so that they were no longer affected. Therefore, intact estuarine communities regulate copper bioavailability and toxicity with ligand production.

Probing protein orientation near charged nanosurfaces for simulation-assisted biosensor design.

PubMed

Cooper, Christopher D; Clementi, Natalia C; Barba, Lorena A

2015-09-28

Protein-surface interactions are ubiquitous in biological processes and bioengineering, yet are not fully understood. In biosensors, a key factor determining the sensitivity and thus the performance of the device is the orientation of the ligand molecules on the bioactive device surface. Adsorption studies thus seek to determine how orientation can be influenced by surface preparation, varying surface charge, and ambient salt concentration. In this work, protein orientation near charged nanosurfaces is obtained under electrostatic effects using the Poisson-Boltzmann equation, in an implicit-solvent model. Sampling the free energy for protein G B1 D4' at a range of tilt and rotation angles with respect to the charged surface, we calculated the probability of the protein orientations and observed a dipolar behavior. This result is consistent with published experimental studies and combined Monte Carlo and molecular dynamics simulations using this small protein, validating our method. More relevant to biosensor technology, antibodies such as immunoglobulin G are still a formidable challenge to molecular simulation, due to their large size. With the Poisson-Boltzmann model, we obtained the probability distribution of orientations for the iso-type IgG2a at varying surface charge and salt concentration. This iso-type was not found to have a preferred orientation in previous studies, unlike the iso-type IgG1 whose larger dipole moment was assumed to make it easier to control. Our results show that the preferred orientation of IgG2a can be favorable for biosensing with positive charge on the surface of 0.05 C/m(2) or higher and 37 mM salt concentration. The results also show that local interactions dominate over dipole moment for this protein. Improving immunoassay sensitivity may thus be assisted by numerical studies using our method (and open-source code), guiding changes to fabrication protocols or protein engineering of ligand molecules to obtain more favorable orientations.

Probing protein orientation near charged nanosurfaces for simulation-assisted biosensor design

NASA Astrophysics Data System (ADS)

Cooper, Christopher D.; Clementi, Natalia C.; Barba, Lorena A.

2015-09-01

Protein-surface interactions are ubiquitous in biological processes and bioengineering, yet are not fully understood. In biosensors, a key factor determining the sensitivity and thus the performance of the device is the orientation of the ligand molecules on the bioactive device surface. Adsorption studies thus seek to determine how orientation can be influenced by surface preparation, varying surface charge, and ambient salt concentration. In this work, protein orientation near charged nanosurfaces is obtained under electrostatic effects using the Poisson-Boltzmann equation, in an implicit-solvent model. Sampling the free energy for protein G B1 D4' at a range of tilt and rotation angles with respect to the charged surface, we calculated the probability of the protein orientations and observed a dipolar behavior. This result is consistent with published experimental studies and combined Monte Carlo and molecular dynamics simulations using this small protein, validating our method. More relevant to biosensor technology, antibodies such as immunoglobulin G are still a formidable challenge to molecular simulation, due to their large size. With the Poisson-Boltzmann model, we obtained the probability distribution of orientations for the iso-type IgG2a at varying surface charge and salt concentration. This iso-type was not found to have a preferred orientation in previous studies, unlike the iso-type IgG1 whose larger dipole moment was assumed to make it easier to control. Our results show that the preferred orientation of IgG2a can be favorable for biosensing with positive charge on the surface of 0.05 C/m2 or higher and 37 mM salt concentration. The results also show that local interactions dominate over dipole moment for this protein. Improving immunoassay sensitivity may thus be assisted by numerical studies using our method (and open-source code), guiding changes to fabrication protocols or protein engineering of ligand molecules to obtain more favorable orientations.

Enhanced sampling of glutamate receptor ligand-binding domains.

PubMed

Lau, Albert Y

2018-04-14

The majority of excitatory synaptic transmission in the central nervous system is mediated by ionotropic glutamate receptors (iGluRs). These membrane-bound protein assemblies consist of modular domains that can be genetically isolated and expressed, which has resulted in a plethora of crystal structures of individual domains in different conformations bound to different ligands. These structures have presented opportunities for molecular dynamics (MD) simulation studies. To examine the free energies that govern molecular behavior, simulation strategies and algorithms have been developed, collectively called enhanced sampling methods This review focuses on the use of enhanced sampling MD simulations of isolated iGluR ligand-binding domains to characterize thermodynamic properties important to receptor function. Copyright © 2018 Elsevier B.V. All rights reserved.

MOST: most-similar ligand based approach to target prediction.

PubMed

Huang, Tao; Mi, Hong; Lin, Cheng-Yuan; Zhao, Ling; Zhong, Linda L D; Liu, Feng-Bin; Zhang, Ge; Lu, Ai-Ping; Bian, Zhao-Xiang

2017-03-11

Many computational approaches have been used for target prediction, including machine learning, reverse docking, bioactivity spectra analysis, and chemical similarity searching. Recent studies have suggested that chemical similarity searching may be driven by the most-similar ligand. However, the extent of bioactivity of most-similar ligands has been oversimplified or even neglected in these studies, and this has impaired the prediction power. Here we propose the MOst-Similar ligand-based Target inference approach, namely MOST, which uses fingerprint similarity and explicit bioactivity of the most-similar ligands to predict targets of the query compound. Performance of MOST was evaluated by using combinations of different fingerprint schemes, machine learning methods, and bioactivity representations. In sevenfold cross-validation with a benchmark Ki dataset from CHEMBL release 19 containing 61,937 bioactivity data of 173 human targets, MOST achieved high average prediction accuracy (0.95 for pKi ≥ 5, and 0.87 for pKi ≥ 6). Morgan fingerprint was shown to be slightly better than FP2. Logistic Regression and Random Forest methods performed better than Naïve Bayes. In a temporal validation, the Ki dataset from CHEMBL19 were used to train models and predict the bioactivity of newly deposited ligands in CHEMBL20. MOST also performed well with high accuracy (0.90 for pKi ≥ 5, and 0.76 for pKi ≥ 6), when Logistic Regression and Morgan fingerprint were employed. Furthermore, the p values associated with explicit bioactivity were found be a robust index for removing false positive predictions. Implicit bioactivity did not offer this capability. Finally, p values generated with Logistic Regression, Morgan fingerprint and explicit activity were integrated with a false discovery rate (FDR) control procedure to reduce false positives in multiple-target prediction scenario, and the success of this strategy it was demonstrated with a case of fluanisone. In the case of aloe-emodin's laxative effect, MOST predicted that acetylcholinesterase was the mechanism-of-action target; in vivo studies validated this prediction. Using the MOST approach can result in highly accurate and robust target prediction. Integrated with a FDR control procedure, MOST provides a reliable framework for multiple-target inference. It has prospective applications in drug repurposing and mechanism-of-action target prediction.

Ligand Binding Pathways and Conformational Transitions of the HIV Protease.

PubMed

Miao, Yinglong; Huang, Yu-Ming M; Walker, Ross C; McCammon, J Andrew; Chang, Chia-En A

2018-03-06

It is important to determine the binding pathways and mechanisms of ligand molecules to target proteins to effectively design therapeutic drugs. Molecular dynamics (MD) is a promising computational tool that allows us to simulate protein-drug binding at an atomistic level. However, the gap between the time scales of current simulations and those of many drug binding processes has limited the usage of conventional MD, which has been reflected in studies of the HIV protease. Here, we have applied a robust enhanced simulation method, Gaussian accelerated molecular dynamics (GaMD), to sample binding pathways of the XK263 ligand and associated protein conformational changes in the HIV protease. During two of 10 independent GaMD simulations performed over 500-2500 ns, the ligand was observed to successfully bind to the protein active site. Although GaMD-derived free energy profiles were not fully converged because of insufficient sampling of the complex system, the simulations still allowed us to identify relatively low-energy intermediate conformational states during binding of the ligand to the HIV protease. Relative to the X-ray crystal structure, the XK263 ligand reached a minimum root-mean-square deviation (RMSD) of 2.26 Å during 2.5 μs of GaMD simulation. In comparison, the ligand RMSD reached a minimum of only ∼5.73 Å during an earlier 14 μs conventional MD simulation. This work highlights the enhanced sampling power of the GaMD approach and demonstrates its wide applicability to studies of drug-receptor interactions for the HIV protease and by extension many other target proteins.

Medical School Factors Associated with Changes in Implicit and Explicit Bias Against Gay and Lesbian People among 3492 Graduating Medical Students.

PubMed

Phelan, Sean M; Burke, Sara E; Hardeman, Rachel R; White, Richard O; Przedworski, Julia; Dovidio, John F; Perry, Sylvia P; Plankey, Michael; A Cunningham, Brooke; Finstad, Deborah; W Yeazel, Mark; van Ryn, Michelle

2017-11-01

Implicit and explicit bias among providers can influence the quality of healthcare. Efforts to address sexual orientation bias in new physicians are hampered by a lack of knowledge of school factors that influence bias among students. To determine whether medical school curriculum, role modeling, diversity climate, and contact with sexual minorities predict bias among graduating students against gay and lesbian people. Prospective cohort study. A sample of 4732 first-year medical students was recruited from a stratified random sample of 49 US medical schools in the fall of 2010 (81% response; 55% of eligible), of which 94.5% (4473) identified as heterosexual. Seventy-eight percent of baseline respondents (3492) completed a follow-up survey in their final semester (spring 2014). Medical school predictors included formal curriculum, role modeling, diversity climate, and contact with sexual minorities. Outcomes were year 4 implicit and explicit bias against gay men and lesbian women, adjusted for bias at year 1. In multivariate models, lower explicit bias against gay men and lesbian women was associated with more favorable contact with LGBT faculty, residents, students, and patients, and perceived skill and preparedness for providing care to LGBT patients. Greater explicit bias against lesbian women was associated with discrimination reported by sexual minority students (b = 1.43 [0.16, 2.71]; p = 0.03). Lower implicit sexual orientation bias was associated with more frequent contact with LGBT faculty, residents, students, and patients (b = -0.04 [-0.07, -0.01); p = 0.008). Greater implicit bias was associated with more faculty role modeling of discriminatory behavior (b = 0.34 [0.11, 0.57); p = 0.004). Medical schools may reduce bias against sexual minority patients by reducing negative role modeling, improving the diversity climate, and improving student preparedness to care for this population.

Incongruence in Doping Related Attitudes, Beliefs and Opinions in the Context of Discordant Behavioural Data: In Which Measure Do We Trust?

PubMed Central

Petróczi, Andrea; Uvacsek, Martina; Nepusz, Tamás; Deshmukh, Nawed; Shah, Iltaf; Aidman, Eugene V.; Barker, James; Tóth, Miklós; Naughton, Declan P.

2011-01-01

Background Social psychology research on doping and outcome based evaluation of primary anti-doping prevention and intervention programmes have been dominated by self-reports. Having confidence in the validity and reliability of such data is vital. Methodology/Principal Findings The sample of 82 athletes from 30 sports (52.4% female, mean age: 21.48±2.86 years) was split into quasi-experimental groups based on i) self-admitted previous experience with prohibited performance enhancing drugs (PED) and ii) the presence of at least one prohibited PED in hair covering up to 6 months prior to data collection. Participants responded to questionnaires assessing a range of social cognitive determinants of doping via self-reports; and completed a modified version of the Brief Implicit Association Test (BIAT) assessing implicit attitudes to doping relative to the acceptable nutritional supplements (NS). Social projection regarding NS was used as control. PEDs were detected in hair samples from 10 athletes (12% prevalence), none of whom admitted doping use. This group of ‘deniers’ was characterised by a dissociation between explicit (verbal declarations) and implicit (BIAT) responding, while convergence was observed in the ‘clean’ athlete group. This dissociation, if replicated, may act as a cognitive marker of the denier group, with promising applications of the combined explicit-implicit cognitive protocol as a proxy in lieu of biochemical detection methods in social science research. Overall, discrepancies in the relationship between declared doping-related opinion and implicit doping attitudes were observed between the groups, with control measures remaining unaffected. Questionnaire responses showed a pattern consistent with self-reported doping use. Conclusions/Significance Following our preliminary work, this study provides further evidence that both self-reports on behaviour and social cognitive measures could be affected by some form of response bias. This can question the validity of self-reports, with reliability remaining unaffected. Triangulation of various assessment methods is recommended. PMID:21541317

Free energy component analysis for drug design: a case study of HIV-1 protease-inhibitor binding.

PubMed

Kalra, P; Reddy, T V; Jayaram, B

2001-12-06

A theoretically rigorous and computationally tractable methodology for the prediction of the free energies of binding of protein-ligand complexes is presented. The method formulated involves developing molecular dynamics trajectories of the enzyme, the inhibitor, and the complex, followed by a free energy component analysis that conveys information on the physicochemical forces driving the protein-ligand complex formation and enables an elucidation of drug design principles for a given receptor from a thermodynamic perspective. The complexes of HIV-1 protease with two peptidomimetic inhibitors were taken as illustrative cases. Four-nanosecond-level all-atom molecular dynamics simulations using explicit solvent without any restraints were carried out on the protease-inhibitor complexes and the free proteases, and the trajectories were analyzed via a thermodynamic cycle to calculate the binding free energies. The computed free energies were seen to be in good accord with the reported data. It was noted that the net van der Waals and hydrophobic contributions were favorable to binding while the net electrostatics, entropies, and adaptation expense were unfavorable in these protease-inhibitor complexes. The hydrogen bond between the CH2OH group of the inhibitor at the scissile position and the catalytic aspartate was found to be favorable to binding. Various implicit solvent models were also considered and their shortcomings discussed. In addition, some plausible modifications to the inhibitor residues were attempted, which led to better binding affinities. The generality of the method and the transferability of the protocol with essentially no changes to any other protein-ligand system are emphasized.

En Route to Depression: Self-Esteem Discrepancies and Habitual Rumination.

PubMed

Phillips, Wendy J; Hine, Donald W

2016-02-01

Dual-process models of cognitive vulnerability to depression suggest that some individuals possess discrepant implicit and explicit self-views, such as high explicit and low implicit self-esteem (fragile self-esteem) or low explicit and high implicit self-esteem (damaged self-esteem). This study investigated whether individuals with discrepant self-esteem may employ depressive rumination in an effort to reduce discrepancy-related dissonance, and whether the relationship between self-esteem discrepancy and future depressive symptoms varies as a function of rumination tendencies. Hierarchical regressions examined whether self-esteem discrepancy was associated with rumination in an Australian undergraduate sample at Time 1 (N = 306; M(age) = 29.9), and whether rumination tendencies moderated the relationship between self-esteem discrepancy and depressive symptoms assessed 3 months later (n = 160). Damaged self-esteem was associated with rumination at Time 1. As hypothesized, rumination moderated the relationship between self-esteem discrepancy and depressive symptoms at Time 2, where fragile self-esteem and high rumination tendencies at Time 1 predicted the highest levels of subsequent dysphoria. Results are consistent with dual-process propositions that (a) explicit self-regulation strategies may be triggered when explicit and implicit self-beliefs are incongruent, and (b) rumination may increase the likelihood of depression by expending cognitive resources and/or amplifying negative implicit biases. © 2014 Wiley Periodicals, Inc.

Delving Beyond Conscious Attitudes: Validation of an Innovative Tool for Assessing Parental Implicit Attitudes toward Physical Punishment

PubMed Central

Sturge-Apple, Melissa L.; Rogge, Ronald D.; Peltz, Jack S.; Suor, Jennifer H.; Skibo, Michael A.

2014-01-01

Parenting scholars have long been interested in understanding the prevalence, determinants, and child outcomes associated with the use of physical discipline. To date, much of the empirical research in this area has utilized self-report measures to assess this construct. However, the subjective nature of participants’ explicit reports presents an important confound to studying this issue. Thus, the overarching aim of this study was to provide the first test of an implicit assessment of physical discipline through using a Go/No-go Association Task (GNAT). A GNAT-Physical Discipline was developed and examined in two separate studies of mothers and their 2-3 year old child. One study was conducted in an online format and the second within a laboratory design. Across both studies, findings suggested that the GNAT-Physical Discipline distinguished between positive and negative implicit attitudes towards the use of physical discipline. In addition, negative implicit attitudes were uniquely linked to maternal reports of physical discipline when compared to other discipline practices. Results suggest the potential for the GNAT paradigm in research on parental attitudes around the use of physical discipline in parenting contexts. In addition, our use of an online format (with implicit assessments of key constructs) demonstrates that child and family researchers may be able to explore their hypotheses in larger, geographically diverse samples. PMID:26195917

Genetic counselors’ implicit racial attitudes and their relationship to communication

PubMed Central

Schaa, Kendra L; Roter, Debra L; Biesecker, Barbara B; Cooper, Lisa A; Erby, Lori H

2015-01-01

Objective Implicit racial attitudes are thought to shape interpersonal interactions and may contribute to health care disparities. This study explored the relationship between genetic counselors’ implicit racial attitudes and their communication during simulated genetic counseling sessions. Methods A nationally representative sample of genetic counselors completed a web-based survey that included the Race Implicit Association Test (IAT). A subset of these counselors (n=67) had participated in an earlier study in which they were video recorded counseling Black, Hispanic and non-Hispanic White simulated clients (SC) about their prenatal or cancer risks. The counselors’ IAT scores were related to their session communication through robust regression modeling. Results Genetic counselors showed a moderate to strong pro-White bias on the Race IAT (M=0.41, SD=0.35). Counselors with stronger pro-White bias were rated as displaying lower levels of positive affect (p<.05) and tended to use less emotionally responsive communication (p<.10) when counseling minority SCs. When counseling White SCs, pro-White bias was associated with lower levels of verbal dominance during sessions (p<.10). Stronger pro-White bias was also associated with more positive ratings of counselors’ nonverbal effectiveness by White SCs. Conclusions Implicit racial bias is associated with negative markers of communication in minority client sessions and may contribute to racial disparities in processes of care related to genetic services. PMID:25622081

Computational fragment-based screening using RosettaLigand: the SAMPL3 challenge

NASA Astrophysics Data System (ADS)

Kumar, Ashutosh; Zhang, Kam Y. J.

2012-05-01

SAMPL3 fragment based virtual screening challenge provides a valuable opportunity for researchers to test their programs, methods and screening protocols in a blind testing environment. We participated in SAMPL3 challenge and evaluated our virtual fragment screening protocol, which involves RosettaLigand as the core component by screening a 500 fragments Maybridge library against bovine pancreatic trypsin. Our study reaffirmed that the real test for any virtual screening approach would be in a blind testing environment. The analyses presented in this paper also showed that virtual screening performance can be improved, if a set of known active compounds is available and parameters and methods that yield better enrichment are selected. Our study also highlighted that to achieve accurate orientation and conformation of ligands within a binding site, selecting an appropriate method to calculate partial charges is important. Another finding is that using multiple receptor ensembles in docking does not always yield better enrichment than individual receptors. On the basis of our results and retrospective analyses from SAMPL3 fragment screening challenge we anticipate that chances of success in a fragment screening process could be increased significantly with careful selection of receptor structures, protein flexibility, sufficient conformational sampling within binding pocket and accurate assignment of ligand and protein partial charges.

Computational Aerothermodynamics in Aeroassist Applications

NASA Technical Reports Server (NTRS)

Gnoffo, Peter A.

2001-01-01

Aeroassisted planetary entry uses atmospheric drag to decelerate spacecraft from super-orbital to orbital or suborbital velocities. Numerical simulation of flow fields surrounding these spacecraft during hypersonic atmospheric entry is required to define aerothermal loads. The severe compression in the shock layer in front of the vehicle and subsequent, rapid expansion into the wake are characterized by high temperature, thermo-chemical nonequilibrium processes. Implicit algorithms required for efficient, stable computation of the governing equations involving disparate time scales of convection, diffusion, chemical reactions, and thermal relaxation are discussed. Robust point-implicit strategies are utilized in the initialization phase; less robust but more efficient line-implicit strategies are applied in the endgame. Applications to ballutes (balloon-like decelerators) in the atmospheres of Venus, Mars, Titan, Saturn, and Neptune and a Mars Sample Return Orbiter (MSRO) are featured. Examples are discussed where time-accurate simulation is required to achieve a steady-state solution.

Implicit vs. explicit dimensions of guilt and dominance in criminal psychopathy.

PubMed

Nentjes, Lieke; Bernstein, David P; Cima, Maaike; Wiers, Reinout W

The current study investigated the relationship between psychopathy and two concepts that hold a central position in conceptualizations of this disorder, being guilt and dominance. Both constructs were measured using explicit measures (i.e., self-report), as well as indirect assessment (i.e., the Single Category Implicit Association Test; Sc-IAT). Our sample consisted of 43 psychopathic offenders, 42 nonpsychopathic offenders, and 26 nonoffender controls. Although no overall group differences emerged, the lifestyle/antisocial traits of psychopathy (Factor 2) predicted reduced self-reported guilt on a dimensional level. As hypothesized, such a relationship was absent for the interpersonal/affective dimension of psychopathy (Factor 1). Psychopathy was unrelated to implicit self-guilt associations. Regarding dominance, psychopathy was not significantly associated with indirectly or explicitly assessed dominance. These findings are interpreted in the light of empirical knowledge on moral emotions, insight and response distortion in highly antisocial offenders. Copyright © 2017 Elsevier Ltd. All rights reserved.

Ligand and receptor dynamics contribute to the mechanism of graded PPARγ agonism

PubMed Central

Hughes, Travis S.; Chalmers, Michael J.; Novick, Scott; Kuruvilla, Dana S.; Chang, Mi Ra; Kamenecka, Theodore M.; Rance, Mark; Johnson, Bruce A.; Burris, Thomas P.; Griffin, Patrick R.; Kojetin, Douglas J.

2011-01-01

SUMMARY Ligand binding to proteins is not a static process, but rather involves a number of complex dynamic transitions. A flexible ligand can change conformation upon binding its target. The conformation and dynamics of a protein can change to facilitate ligand binding. The conformation of the ligand, however, is generally presumed to have one primary binding mode, shifting the protein conformational ensemble from one state to another. We report solution NMR studies that reveal peroxisome proliferator-activated receptor γ (PPARγ) modulators can sample multiple binding modes manifesting in multiple receptor conformations in slow conformational exchange. Our NMR, hydrogen/deuterium exchange and docking studies reveal that ligand-induced receptor stabilization and binding mode occupancy correlate with the graded agonist response of the ligand. Our results suggest that ligand and receptor dynamics affect the graded transcriptional output of PPARγ modulators. PMID:22244763

Accurate representation of B-DNA double helical structure with implicit solvent and counterions.

PubMed Central

Wang, Lihua; Hingerty, Brian E; Srinivasan, A R; Olson, Wilma K; Broyde, Suse

2002-01-01

High-resolution nuclear magnetic resonance (NMR) and crystallographic data have been taken to refine the force field used in the torsion angle space nucleic acids molecular mechanics program DUPLEX. The population balance deduced from NMR studies of two carcinogen-modified DNA conformers in equilibrium was used to fine tune a sigmoidal, distance-dependent dielectric function so that reasonable relative energies could be obtained. In addition, the base-pair and backbone geometry from high-resolution crystal structures of the Dickerson-Drew dodecamer was used to re-evaluate the deoxyribose pseudorotation profile and the Lennard-Jones nonbonded energy terms. With a modified dielectric function that assumes a very steep distance-dependent form, a deoxyribose pseudorotation profile with reduced energy barriers between C2'- and C3'-endo minima, and a shift of the Lennard-Jones potential energy minimum to a distance approximately 0.4 A greater than the sum of the van der Waals' radii, the sequence-dependent conformational features of the Dickerson-Drew dodecamer in both the solid state and the aqueous liquid crystalline phase are well reproduced. The robust performance of the revised force field, in conjunction with its efficiency through implicit treatment of solvent and counterions, provides a valuable tool for elucidating conformations and structure-function relationships of DNA, including those of molecules modified by carcinogens and other ligands. PMID:12080128

Radiolytic degradation of a new diglycol-diamide ligand for actinide and lanthanide co-extraction from spent nuclear fuel

NASA Astrophysics Data System (ADS)

Ossola, Annalisa; Macerata, Elena; Tinonin, Dario A.; Faroldi, Federica; Giola, Marco; Mariani, Mario; Casnati, Alessandro

2016-07-01

Within the Partitioning and Transmutation strategies, great efforts have been devoted in the last decades to the development of lipophilic ligands able to co-extract trivalent Lanthanides (Ln) and Actinides (An) from spent nuclear fuel. Because of the harsh working conditions these ligands undergo, it is important to prove their chemical and radiolytic stability during the counter-current multi-stage extraction process. In the present work the hydrolytic and radiolytic resistance of the freshly prepared and aged organic solutions containing the new ligand (2,6-bis[(N-methyl-N-dodecyl)carboxamide]-4-methoxy-tetrahydro-pyran) were investigated in order to evaluate the impact on the safety and efficiency of the process. Liquid-liquid extraction tests with spiked solutions showed that the ligand extracting performances are strongly impaired by storing the samples at room temperature and in the light. Moreover, the extracting efficiency of the irradiated samples resulted to be influenced by gamma irradiation, while selectivity remains unchanged. Preliminary mass spectrometric data showed that degradation is mainly due to the acid-catalysed reaction of the ligand carboxamide and ether groups with the 1-octanol present in the diluent.

Integrating Implicit Leadership Theories, Leader-Member Exchange, Self-Efficacy, and Attachment Theory to Predict Job Performance.

PubMed

Khorakian, Alireza; Sharifirad, Mohammad Sadegh

2018-01-01

The impact of implicit leadership theories on performance and the mechanism linking them have received insufficient theoretical and research attention. Drawing on Bandura's social cognitive theory, the present study contributes theory through examining the assertion that higher congruence between followers' implicit leadership theory and the characteristics of supervisors enhance job performance through higher quality of leader-member exchange and self-efficacy. Moreover, in the proposed model, attachment insecurity was considered as the antecedent of the congruence and leader-member exchange in addition to the moderator of the relationship between them. Capitalizing upon Structural Equation Modeling (SEM), this study tested the model in a field study using a sample of employees in knowledge-oriented firms in Iran. The results suggest that the congruence between followers' implicit leadership theory and the characteristics of supervisors does not directly impact performance and leader-member exchange and self-efficacy are the full mediators. The results also showed that attachment insecurity is the predictor of neither the congruence nor the leader-member exchange. Additionally, attachment insecurity moderates the relationship between these two variables in a way that when attachment insecurity is high, the congruence has more positive impact on leader-member exchange.

Warriors and peacekeepers: testing a biosocial implicit leadership hypothesis of intergroup relations using masculine and feminine faces.

PubMed

Spisak, Brian R; Dekker, Peter H; Krüger, Max; van Vugt, Mark

2012-01-01

This paper examines the impact of facial cues on leadership emergence. Using evolutionary social psychology, we expand upon implicit and contingent theories of leadership and propose that different types of intergroup relations elicit different implicit cognitive leadership prototypes. It is argued that a biologically based hormonal connection between behavior and corresponding facial characteristics interacts with evolutionarily consistent social dynamics to influence leadership emergence. We predict that masculine-looking leaders are selected during intergroup conflict (war) and feminine-looking leaders during intergroup cooperation (peace). Across two experiments we show that a general categorization of leader versus nonleader is an initial implicit requirement for emergence, and at a context-specific level facial cues of masculinity and femininity contingently affect war versus peace leadership emergence in the predicted direction. In addition, we replicate our findings in Experiment 1 across culture using Western and East Asian samples. In Experiment 2, we also show that masculine-feminine facial cues are better predictors of leadership than male-female cues. Collectively, our results indicate a multi-level classification of context-specific leadership based on visual cues imbedded in the human face and challenge traditional distinctions of male and female leadership.

Warriors and Peacekeepers: Testing a Biosocial Implicit Leadership Hypothesis of Intergroup Relations Using Masculine and Feminine Faces

PubMed Central

Spisak, Brian R.; Dekker, Peter H.; Krüger, Max; van Vugt, Mark

2012-01-01

This paper examines the impact of facial cues on leadership emergence. Using evolutionary social psychology, we expand upon implicit and contingent theories of leadership and propose that different types of intergroup relations elicit different implicit cognitive leadership prototypes. It is argued that a biologically based hormonal connection between behavior and corresponding facial characteristics interacts with evolutionarily consistent social dynamics to influence leadership emergence. We predict that masculine-looking leaders are selected during intergroup conflict (war) and feminine-looking leaders during intergroup cooperation (peace). Across two experiments we show that a general categorization of leader versus nonleader is an initial implicit requirement for emergence, and at a context-specific level facial cues of masculinity and femininity contingently affect war versus peace leadership emergence in the predicted direction. In addition, we replicate our findings in Experiment 1 across culture using Western and East Asian samples. In Experiment 2, we also show that masculine-feminine facial cues are better predictors of leadership than male-female cues. Collectively, our results indicate a multi-level classification of context-specific leadership based on visual cues imbedded in the human face and challenge traditional distinctions of male and female leadership. PMID:22276190

Do Contact and Empathy Mitigate Bias Against Gay and Lesbian People Among Heterosexual First-Year Medical Students? A Report From the Medical Student CHANGE Study.

PubMed

Burke, Sara E; Dovidio, John F; Przedworski, Julia M; Hardeman, Rachel R; Perry, Sylvia P; Phelan, Sean M; Nelson, David B; Burgess, Diana J; Yeazel, Mark W; van Ryn, Michelle

2015-05-01

A recent Institute of Medicine report concluded that lesbian and gay individuals face discrimination from health care providers and called for research on provider attitudes. Medical school is a critical juncture for improving future providers' treatment of sexual minorities. This study examined both explicit bias and implicit bias against lesbian women and gay men among first-year medical students, focusing on two predictors of such bias, contact and empathy. This study included the 4,441 heterosexual first-year medical students who participated in the baseline survey of the Medical Student Cognitive Habits and Growth Evaluation Study, which employed a stratified random sample of 49 U.S. medical schools in fall 2010. The researchers measured explicit attitudes toward gay and lesbian people using feeling thermometer self-assessments, implicit attitudes using the Implicit Association Test, amount and favorability of contact using self-report items, and empathy using subscales of the Interpersonal Reactivity Index. Nearly half (45.79%; 956/2,088) of respondents with complete data on both bias measures expressed at least some explicit bias, and most (81.51%; 1,702/2,088) exhibited at least some implicit bias against gay and lesbian individuals. Both amount and favorability of contact predicted positive implicit and explicit attitudes. Both cognitive and emotional empathy predicted positive explicit attitudes, but not implicit attitudes. The prevalence of negative attitudes presents an important challenge for medical education, highlighting the need for more research on possible causes of bias. Findings on contact and empathy point to possible curriculum-based interventions aimed at ensuring high-quality care for sexual minorities.

On the gender-science stereotypes held by scientists: explicit accord with gender-ratios, implicit accord with scientific identity.

PubMed

Smyth, Frederick L; Nosek, Brian A

2015-01-01

Women's representation in science has changed substantially, but unevenly, over the past 40 years. In health and biological sciences, for example, women's representation among U.S. scientists is now on par with or greater than men's, while in physical sciences and engineering they remain a clear minority. We investigated whether variation in proportions of women in scientific disciplines is related to differing levels of male-favoring explicit or implicit stereotypes held by students and scientists in each discipline. We hypothesized that science-is-male stereotypes would be weaker in disciplines where women are better represented. This prediction was tested with a sample of 176,935 college-educated participants (70% female), including thousands of engineers, physicians, and scientists. The prediction was supported for the explicit stereotype, but not for the implicit stereotype. Implicit stereotype strength did not correspond with disciplines' gender ratios, but, rather, correlated with two indicators of disciplines' scientific intensity, positively for men and negatively for women. From age 18 on, women who majored or worked in disciplines perceived as more scientific had substantially weaker science-is-male stereotypes than did men in the same disciplines, with gender differences larger than 0.8 standard deviations in the most scientifically-perceived disciplines. Further, particularly for women, differences in the strength of implicit stereotypes across scientific disciplines corresponded with the strength of scientific values held by women in the disciplines. These results are discussed in the context of dual process theory of mental operation and balanced identity theory. The findings point to the need for longitudinal study of the factors' affecting development of adults' and, especially, children's implicit gender stereotypes and scientific identity.

On the gender–science stereotypes held by scientists: explicit accord with gender-ratios, implicit accord with scientific identity

PubMed Central

Smyth, Frederick L.; Nosek, Brian A.

2015-01-01

Women's representation in science has changed substantially, but unevenly, over the past 40 years. In health and biological sciences, for example, women's representation among U.S. scientists is now on par with or greater than men's, while in physical sciences and engineering they remain a clear minority. We investigated whether variation in proportions of women in scientific disciplines is related to differing levels of male-favoring explicit or implicit stereotypes held by students and scientists in each discipline. We hypothesized that science-is-male stereotypes would be weaker in disciplines where women are better represented. This prediction was tested with a sample of 176,935 college-educated participants (70% female), including thousands of engineers, physicians, and scientists. The prediction was supported for the explicit stereotype, but not for the implicit stereotype. Implicit stereotype strength did not correspond with disciplines' gender ratios, but, rather, correlated with two indicators of disciplines' scientific intensity, positively for men and negatively for women. From age 18 on, women who majored or worked in disciplines perceived as more scientific had substantially weaker science-is-male stereotypes than did men in the same disciplines, with gender differences larger than 0.8 standard deviations in the most scientifically-perceived disciplines. Further, particularly for women, differences in the strength of implicit stereotypes across scientific disciplines corresponded with the strength of scientific values held by women in the disciplines. These results are discussed in the context of dual process theory of mental operation and balanced identity theory. The findings point to the need for longitudinal study of the factors' affecting development of adults' and, especially, children's implicit gender stereotypes and scientific identity. PMID:25964765

Tunable, mixed-resolution modeling using library-based Monte Carlo and graphics processing units

PubMed Central

Mamonov, Artem B.; Lettieri, Steven; Ding, Ying; Sarver, Jessica L.; Palli, Rohith; Cunningham, Timothy F.; Saxena, Sunil; Zuckerman, Daniel M.

2012-01-01

Building on our recently introduced library-based Monte Carlo (LBMC) approach, we describe a flexible protocol for mixed coarse-grained (CG)/all-atom (AA) simulation of proteins and ligands. In the present implementation of LBMC, protein side chain configurations are pre-calculated and stored in libraries, while bonded interactions along the backbone are treated explicitly. Because the AA side chain coordinates are maintained at minimal run-time cost, arbitrary sites and interaction terms can be turned on to create mixed-resolution models. For example, an AA region of interest such as a binding site can be coupled to a CG model for the rest of the protein. We have additionally developed a hybrid implementation of the generalized Born/surface area (GBSA) implicit solvent model suitable for mixed-resolution models, which in turn was ported to a graphics processing unit (GPU) for faster calculation. The new software was applied to study two systems: (i) the behavior of spin labels on the B1 domain of protein G (GB1) and (ii) docking of randomly initialized estradiol configurations to the ligand binding domain of the estrogen receptor (ERα). The performance of the GPU version of the code was also benchmarked in a number of additional systems. PMID:23162384

Kissing loop interaction in adenine riboswitch: insights from umbrella sampling simulations.

PubMed

Di Palma, Francesco; Bottaro, Sandro; Bussi, Giovanni

2015-01-01

Riboswitches are cis-acting regulatory RNA elements prevalently located in the leader sequences of bacterial mRNA. An adenine sensing riboswitch cis-regulates adeninosine deaminase gene (add) in Vibrio vulnificus. The structural mechanism regulating its conformational changes upon ligand binding mostly remains to be elucidated. In this open framework it has been suggested that the ligand stabilizes the interaction of the distal "kissing loop" complex. Using accurate full-atom molecular dynamics with explicit solvent in combination with enhanced sampling techniques and advanced analysis methods it could be possible to provide a more detailed perspective on the formation of these tertiary contacts. In this work, we used umbrella sampling simulations to study the thermodynamics of the kissing loop complex in the presence and in the absence of the cognate ligand. We enforced the breaking/formation of the loop-loop interaction restraining the distance between the two loops. We also assessed the convergence of the results by using two alternative initialization protocols. A structural analysis was performed using a novel approach to analyze base contacts. Contacts between the two loops were progressively lost when larger inter-loop distances were enforced. Inter-loop Watson-Crick contacts survived at larger separation when compared with non-canonical pairing and stacking interactions. Intra-loop stacking contacts remained formed upon loop undocking. Our simulations qualitatively indicated that the ligand could stabilize the kissing loop complex. We also compared with previously published simulation studies. Kissing complex stabilization given by the ligand was compatible with available experimental data. However, the dependence of its value on the initialization protocol of the umbrella sampling simulations posed some questions on the quantitative interpretation of the results and called for better converged enhanced sampling simulations.

Making sense of the noise: Replication difficulties of Correll's (2008) modulation of 1/f noise in a racial bias task.

PubMed

Madurski, Christine; LeBel, Etienne P

2015-08-01

Correll (Journal of Personality and Social Psychology, 94, 48-59, 2008; Study 2) found that instructions to use or avoid race information decreased the emission of 1/f noise in a weapon identification task (WIT). These results suggested that 1/f noise in racial bias tasks reflected an effortful deliberative process, providing new insights regarding the mechanisms underlying implicit racial biases. Given the potential theoretical and applied importance of understanding the psychological processes underlying implicit racial biases - and in light of the growing demand for independent direct replications of findings to ensure the cumulative nature of our science - we attempted to replicate Correll's finding in two high-powered studies. Despite considerable effort to closely duplicate all procedural and methodological details of the original study (i.e., same cover story, experimental manipulation, implicit measure task, original stimuli, task instructions, sampling frame, population, and statistical analyses), both replication attempts were unsuccessful in replicating the original finding challenging the theoretical account that 1/f noise in racial bias tasks reflects a deliberative process. However, the emission of 1/f noise did consistently emerge across samples in each of our conditions. Hence, future research is needed to clarify the psychological significance of 1/f noise in racial bias tasks.

Implicit and explicit learning in schizophrenics treated with olanzapine and with classic neuroleptics.

PubMed

Stevens, Andreas; Schwarz, Jürgen; Schwarz, Benedikt; Ruf, Ilona; Kolter, Thomas; Czekalla, Joerg

2002-03-01

Novel and classic neuroleptics differ in their effects on limbic striatal/nucleus accumbens (NA) and prefrontal cortex (PFC) dopamine turnover, suggesting differential effects on implicit and explicit learning as well as on anhedonia. The present study investigates whether such differences can be demonstrated in a naturalistic sample of schizophrenic patients. Twenty-five inpatients diagnosed with DSM-IV schizophrenic psychosis and treated for at least 14 days with the novel neuroleptic olanzapine were compared with 25 schizophrenics taking classic neuroleptics and with 25 healthy controls, matched by age and education level. PFC/NA-dependent implicit learning was assessed by a serial reaction time task (SRTT) and compared with cerebellum-mediated classical eye-blink conditioning and explicit visuospatial memory. Anhedonia was measured with the Snaith-Hamilton-Pleasure Scale (SHAPS). Implicit (SRTT) and psychomotor speed, but not explicit (visuospatial) learning were superior in the olanzapine-treated group as compared to the patients on classic neuroleptics. Compared to healthy controls, olanzapine-treated schizophrenics showed similar implicit learning, but reduced explicit (visuospatial) memory performance. Acquisition of eyeblink conditioning was not different between the three groups. There was no difference with regard to anhedonia and SANS scores between the patients. Olanzapine seems to interfere less with unattended learning and motor speed than classical neuroleptics. In daily life, this may translate into better adaptation to a rapidly changing environment. The effects seem specific, as in explicit learning and eyeblink conditioning no difference to classic NL was found.

Determination of Cu Environments in the Cyanobacterium Anabaena flos-aquae by X-Ray Absorption Spectroscopy

PubMed Central

Kretschmer, X. C.; Meitzner, G.; Gardea-Torresdey, J. L.; Webb, R.

2004-01-01

Whole cells and peptidoglycan isolated from cell walls of the cyanobacterium Anabaena flos-aquae were lyophilized and used at pH 2 and pH 5 in Cu(II) binding studies. X-ray absorption spectra measured at the Cu K-edge were used to determine the oxidation states and chemical environments of Cu species in the whole-cell and peptidoglycan samples. In the whole-cell samples, most of the Cu retained at both pH values was coordinated by phosphate ligands. The whole-cell fractions contained significant concentrations of Cu(I) as well as Cu(II). An X-ray absorption near-edge spectrum analysis suggested that Cu(I) was coordinated by amine and thiol ligands. An analysis of the peptidoglycan fractions found that more Cu was adsorbed by the peptidoglycan fraction prepared at pH 5, due to increased chelation by amine and carboxyl ligands. The peptidoglycan fractions, also referred to as the cell wall fractions, contained little or no Cu(I). The Cu loading level was 30 times higher in the cell wall sample prepared at pH 5 than in the sample prepared at pH 2. Amine and bidentate carboxyl ligands had similar relative levels of importance in cell wall peptidoglycan samples prepared at both pH values, but phosphate coordination was insignificant. PMID:14766554

Fully Flexible Docking of Medium Sized Ligand Libraries with RosettaLigand

PubMed Central

DeLuca, Samuel; Khar, Karen; Meiler, Jens

2015-01-01

RosettaLigand has been successfully used to predict binding poses in protein-small molecule complexes. However, the RosettaLigand docking protocol is comparatively slow in identifying an initial starting pose for the small molecule (ligand) making it unfeasible for use in virtual High Throughput Screening (vHTS). To overcome this limitation, we developed a new sampling approach for placing the ligand in the protein binding site during the initial ‘low-resolution’ docking step. It combines the translational and rotational adjustments to the ligand pose in a single transformation step. The new algorithm is both more accurate and more time-efficient. The docking success rate is improved by 10–15% in a benchmark set of 43 protein/ligand complexes, reducing the number of models that typically need to be generated from 1000 to 150. The average time to generate a model is reduced from 50 seconds to 10 seconds. As a result we observe an effective 30-fold speed increase, making RosettaLigand appropriate for docking medium sized ligand libraries. We demonstrate that this improved initial placement of the ligand is critical for successful prediction of an accurate binding position in the ‘high-resolution’ full atom refinement step. PMID:26207742

Interactions of Multimodal Ligands with Proteins: Insights into Selectivity Using Molecular Dynamics Simulations.

PubMed

Parimal, Siddharth; Garde, Shekhar; Cramer, Steven M

2015-07-14

Fundamental understanding of protein-ligand interactions is important to the development of efficient bioseparations in multimodal chromatography. Here we employ molecular dynamics (MD) simulations to investigate the interactions of three different proteins--ubiquitin, cytochrome C, and α-chymotrypsinogen A, sampling a range of charge from +1e to +9e--with two multimodal chromatographic ligands containing similar chemical moieties--aromatic, carboxyl, and amide--in different structural arrangements. We use a spherical harmonic expansion to analyze ligand and individual moiety density profiles around the proteins. We find that the Capto MMC ligand, which contains an additional aliphatic group, displays stronger interactions than Nuvia CPrime ligand with all three proteins. Studying the ligand densities at the moiety level suggests that hydrophobic interactions play a major role in determining the locations of high ligand densities. Finally, the greater structural flexibility of the Capto MMC ligand compared to that of the Nuvia cPrime ligand allows for stronger structural complementarity and enables stronger hydrophobic interactions. These subtle and not-so-subtle differences in binding affinities and modalities for multimodal ligands can result in significantly different binding behavior towards proteins with important implications for bioprocessing.

Distinct Iron-binding Ligands in the Upper Water Column at Station ALOHA

NASA Astrophysics Data System (ADS)

Bundy, R.; Boiteau, R.; Repeta, D.

2016-02-01

The distribution and chemical properties of iron-binding organic ligands at station ALOHA were examined using a combination of solid phase extraction (SPE) followed by high pressure liquid chromatography-inductively coupled plasma mass spectrometry (HPLC-ICPMS). HPLC-ICPMS ligand measurements were complemented by competitive ligand exchange adsorptive cathodic stripping voltammetry (CLE-ACSV) analysis using salicylaldoxime as the added ligand. By HPLC-ICPMS, we find enhanced concentrations of distinct naturally-occurring polar iron-binding ligands present at the surface and in the chlorophyll maximum. Lower concentrations were found in the subsurface, where a suite of non-polar ligands was detected. Siderophores were present at the deepest depths sampled at station ALOHA, down to 400m. Incubation studies provided evidence for the production of iron-binding ligands associated with nutrient amended phytoplankton growth in surface waters, and as a result of microbial particle remineralization in the subsurface water column. Ligands classes identified via SPE were then compared to CLE-ACSV ligand measurements, as well as the conditional stability constants measured from model polar and non-polar siderophores, yielding insight to the sources of iron-binding ligands throughout the water column at station ALOHA.

Ligand-Independent Epidermal Growth Factor Receptor Overexpression Correlates with Poor Prognosis in Colorectal Cancer.

PubMed

Yun, Sumi; Kwak, Yoonjin; Nam, Soo Kyung; Seo, An Na; Oh, Heung-Kwon; Kim, Duck-Woo; Kang, Sung-Bum; Lee, Hye Seung

2018-01-17

Molecular treatments targeting epidermal growth factor receptors (EGFRs) are important strategies for advanced colorectal cancer (CRC). However, clinicopathologic implications of EGFRs and EGFR ligand signaling have not been fully evaluated. We evaluated the expression of EGFR ligands and correlation with their receptors, clinicopathologic factors, and patients' survival with CRC. The expression of EGFR ligands, including heparin binding epidermal growth factor like growth factor (HBEGF), transforming growth factor (TGF), betacellulin, and epidermal growth factor (EGF), were evaluated in 331 consecutive CRC samples using mRNA in situ hybridization (ISH). We also evaluated the expression status of EGFR, human epidermal growth factor receptor 2 (HER2), HER3, and HER4 using immunohistochemistry and/or silver ISH. Unlike low incidences of TGF (38.1%), betacellulin (7.9%), and EGF (2.1%), HBEGF expression was noted in 62.2% of CRC samples. However, the expression of each EGFR ligand did not reveal significant correlations with survival. The combined analyses of EGFR ligands and EGFR expression indicated that the ligands‒/EGFR+ group showed a significant association with the worst disease-free survival (DFS, p=0.018) and overall survival (OS, p=0.005). It was also an independent, unfavorable prognostic factor for DFS (p=0.026) and OS (p=0.007). Additionally, HER4 nuclear expression, regardless of ligand expression, was an independent, favorable prognostic factor for DFS (p=0.034) and OS (p=0.049), by multivariate analysis. Ligand-independent EGFR overexpression was suggested to have a significant prognostic impact; thus, the expression status of EGFR ligands, in addition to EGFR, might be necessary for predicting patients' outcome in CRC.

Exploring Flexibility of Progesterone Receptor Ligand Binding Domain Using Molecular Dynamics

PubMed Central

Zheng, Liangzhen; Mu, Yuguang

2016-01-01

Progesterone receptor (PR), a member of nuclear receptor (NR) superfamily, plays a vital role for female reproductive tissue development, differentiation and maintenance. PR ligand, such as progesterone, induces conformation changes in PR ligand binding domain (LBD), thus mediates subsequent gene regulation cascades. PR LBD may adopt different conformations upon an agonist or an antagonist binding. These different conformations would trigger distinct transcription events. Therefore, the dynamics of PR LBD would be of general interest to biologists for a deep understanding of its structure-function relationship. However, no apo-form (non-ligand bound) of PR LBD model has been proposed either by experiments or computational methods so far. In this study, we explored the structural dynamics of PR LBD using molecular dynamics simulations and advanced sampling tools in both ligand-bound and the apo-forms. Resolved by the simulation study, helix 11, helix 12 and loop 895–908 (the loop between these two helices) are quite flexible in antagonistic conformation. Several residues, such as Arg899 and Glu723, could form salt-bridging interaction between helix 11 and helix 3, and are important for the PR LBD dynamics. And we also propose that helix 12 in apo-form PR LBD, not like other NR LBDs, such as human estrogen receptor α (ERα) LBD, may not adopt a totally extended conformation. With the aid of umbrella sampling and metadynamics simulations, several stable conformations of apo-form PR LBD have been sampled, which may work as critical structural models for further large scale virtual screening study to discover novel PR ligands for therapeutic application. PMID:27824891

Free-Energy Landscape of Protein-Ligand Interactions Coupled with Protein Structural Changes.

PubMed

Moritsugu, Kei; Terada, Tohru; Kidera, Akinori

2017-02-02

Protein-ligand interactions are frequently coupled with protein structural changes. Focusing on the coupling, we present the free-energy surface (FES) of the ligand-binding process for glutamine-binding protein (GlnBP) and its ligand, glutamine, in which glutamine binding accompanies large-scale domain closure. All-atom simulations were performed in explicit solvents by multiscale enhanced sampling (MSES), which adopts a multicopy and multiscale scheme to achieve enhanced sampling of systems with a large number of degrees of freedom. The structural ensemble derived from the MSES simulation yielded the FES of the coupling, described in terms of both the ligand's and protein's degrees of freedom at atomic resolution, and revealed the tight coupling between the two degrees of freedom. The derived FES led to the determination of definite structural states, which suggested the dominant pathways of glutamine binding to GlnBP: first, glutamine migrates via diffusion to form a dominant encounter complex with Arg75 on the large domain of GlnBP, through strong polar interactions. Subsequently, the closing motion of GlnBP occurs to form ligand interactions with the small domain, finally completing the native-specific complex structure. The formation of hydrogen bonds between glutamine and the small domain is considered to be a rate-limiting step, inducing desolvation of the protein-ligand interface to form the specific native complex. The key interactions to attain high specificity for glutamine, the "door keeper" existing between the two domains (Asp10-Lys115) and the "hydrophobic sandwich" formed between the ligand glutamine and Phe13/Phe50, have been successfully mapped on the pathway derived from the FES.

A new titration system of a novel split-type superconducting magnet NMR spectrometer.

PubMed

Kitagawa, Isao; Tanaka, Hideki; Okada, Michiya; Kitaguchi, Hitoshi; Kohzuma, Takamitsu

2008-12-01

A new titration system for studying protein-ligand interactions has been developed. In this system, the sample solution is circulated in the route formed by an access path in a split superconducting magnet to maintain a constant protein concentration during the titration experiments. A concentration-control procedure for the ligand/protein ratio is devised, and the ligand/protein ratio is well controlled by this apparatus.

Development of a Computational Assay for the Estrogen Receptor

DTIC Science & Technology

2006-07-01

University Ashley Deline, Senior Thesis in chemistry, " Molecular Dynamic Simulations of a Glycoform and its Constituent Parts Related to Rheumatoid Arthritis...involves running a long molecular dynamics (MD) simulation of the uncoupled receptor in order to sample the protein’s unique conformations. The second...Receptor binding domain. * Performed several long molecular dynamics simulations (800 ps - 3 ns) on the ligand-ER system using ligands with known

Ligand-biased ensemble receptor docking (LigBEnD): a hybrid ligand/receptor structure-based approach

NASA Astrophysics Data System (ADS)

Lam, Polo C.-H.; Abagyan, Ruben; Totrov, Maxim

2018-01-01

Ligand docking to flexible protein molecules can be efficiently carried out through ensemble docking to multiple protein conformations, either from experimental X-ray structures or from in silico simulations. The success of ensemble docking often requires the careful selection of complementary protein conformations, through docking and scoring of known co-crystallized ligands. False positives, in which a ligand in a wrong pose achieves a better docking score than that of native pose, arise as additional protein conformations are added. In the current study, we developed a new ligand-biased ensemble receptor docking method and composite scoring function which combine the use of ligand-based atomic property field (APF) method with receptor structure-based docking. This method helps us to correctly dock 30 out of 36 ligands presented by the D3R docking challenge. For the six mis-docked ligands, the cognate receptor structures prove to be too different from the 40 available experimental Pocketome conformations used for docking and could be identified only by receptor sampling beyond experimentally explored conformational subspace.

Parameter recovery, bias and standard errors in the linear ballistic accumulator model.

PubMed

Visser, Ingmar; Poessé, Rens

2017-05-01

The linear ballistic accumulator (LBA) model (Brown & Heathcote, , Cogn. Psychol., 57, 153) is increasingly popular in modelling response times from experimental data. An R package, glba, has been developed to fit the LBA model using maximum likelihood estimation which is validated by means of a parameter recovery study. At sufficient sample sizes parameter recovery is good, whereas at smaller sample sizes there can be large bias in parameters. In a second simulation study, two methods for computing parameter standard errors are compared. The Hessian-based method is found to be adequate and is (much) faster than the alternative bootstrap method. The use of parameter standard errors in model selection and inference is illustrated in an example using data from an implicit learning experiment (Visser et al., , Mem. Cogn., 35, 1502). It is shown that typical implicit learning effects are captured by different parameters of the LBA model. © 2017 The British Psychological Society.

Free energy landscapes of small peptides in an implicit solvent model determined by force-biased multicanonical molecular dynamics simulation

NASA Astrophysics Data System (ADS)

Watanabe, Yukihisa S.; Kim, Jae Gil; Fukunishi, Yoshifumi; Nakamura, Haruki

2004-12-01

In order to investigate whether the implicit solvent (GB/SA) model could reproduce the free energy landscapes of peptides, the potential of mean forces (PMFs) of eight tripeptides was examined and compared with the PMFs of the explicit water model. The force-biased multicanonical molecular dynamics method was used for the enhanced conformational sampling. Consequently, the GB/SA model reproduced almost all the global and local minima in the PMFs observed with the explicit water model. However, the GB/SA model overestimated frequencies of the structures that are stabilized by intra-peptide hydrogen bonds.

Self-esteem discrepancies and identity-expressive consumption: Evidence from Norwegian adolescents.

PubMed

Tunca, Burak

2018-02-01

Prior research established that simultaneously holding discrepant explicit (deliberate, controlled) and implicit (automatic, uncontrolled) self-esteem gives rise to self-enhancing behaviours. Given that individuals tend to enhance their self-concepts with brands that are associated with positive identities, this study examined whether self-esteem discrepancy was related to the extent to which individuals developed connections with brands that are associated with their in-groups. Findings from an adolescent sample (ages 16-18) indicated that adolescents with larger discrepancies between explicit and implicit self-esteem were more likely to construct their self-concepts using in-group-linked brands. © 2016 International Union of Psychological Science.

Heterogeneity and dynamics of the ligand recognition mode in purine-sensing riboswitches.

PubMed

Jain, Niyati; Zhao, Liang; Liu, John D; Xia, Tianbing

2010-05-04

High-resolution crystal structures and biophysical analyses of purine-sensing riboswitches have revealed that a network of hydrogen bonding interactions appear to be largey responsible for discrimination of cognate ligands against structurally related compounds. Here we report that by using femtosecond time-resolved fluorescence spectroscopy to capture the ultrafast decay dynamics of the 2-aminopurine base as the ligand, we have detected the presence of multiple conformations of the ligand within the binding pockets of one guanine-sensing and two adenine-sensing riboswitches. All three riboswitches have similar conformational distributions of the ligand-bound state. The known crystal structures represent the global minimum that accounts for 50-60% of the population, where there is no significant stacking interaction between the ligand and bases of the binding pocket, but the hydrogen-bonding cage collectively provides an electronic environment that promotes an ultrafast ( approximately 1 ps) charge transfer pathway. The ligand also samples multiple conformations in which it significantly stacks with either the adenine or the uracil bases of the A21-U75 and A52-U22 base pairs that form the ceiling and floor of the binding pocket, respectively, but favors the larger adenine bases. These alternative conformations with well-defined base stacking interactions are approximately 1-1.5 kcal/mol higher in DeltaG degrees than the global minimum and have distinct charge transfer dynamics within the picosecond to nanosecond time regime. Inside the pocket, the purine ligand undergoes dynamic motion on the low nanosecond time scale, sampling the multiple conformations based on time-resolved anisotropy decay dynamics. These results allowed a description of the energy landscape of the bound ligand with intricate details and demonstrated the elastic nature of the ligand recognition mode by the purine-sensing riboswitches, where there is a dynamic balance between hydrogen bonding and base stacking interactions, yielding the high affinity and specificity by the aptamer domain.

Programmable calculator software for computation of the plasma binding of ligands.

PubMed

Conner, D P; Rocci, M L; Larijani, G E

1986-01-01

The computation of the extent of plasma binding of a ligand to plasma constituents using radiolabeled ligand and equilibrium dialysis is complex and tedious. A computer program for the HP-41C Handheld Computer Series (Hewlett-Packard) was developed to perform these calculations. The first segment of the program constructs a standard curve for quench correction of post-dialysis plasma and buffer samples, using either external standard ratio (ESR) or sample channels ratio (SCR) techniques. The remainder of the program uses the counts per minute, SCR or ESR, and post-dialysis volume of paired plasma and buffer samples generated from the dialysis procedure to compute the extent of binding after correction for background radiation, counting efficiency, and intradialytic shifts of fluid between plasma and buffer compartments during dialysis. This program greatly simplifies the analysis of equilibrium dialysis data and has been employed in the analysis of dexamethasone binding in normal and uremic sera.

Predicting Return of Fear Following Exposure Therapy With an Implicit Measure of Attitudes

PubMed Central

Vasey, Michael W.; Harbaugh, Casaundra N.; Buffington, Adam G.; Jones, Christopher R.; Fazio, Russell H.

2012-01-01

We sought to advance understanding of the processes underlying the efficacy of exposure therapy and particularly the phenomenon of return of fear (ROF) following treatment by drawing on a social psychological view of phobias as attitudes. Specifically, a dual process theory of attitude-related behavior predicts that a positive response to exposure therapy may reflect change in either the automatic (the attitude representation itself) or controlled (skills and confidence at coping with the fear) responses to the phobic stimulus, or both. However, if the attitude representation remains negative following treatment, ROF should be more likely. We tested this hypothesis in a clinical sample of individuals with public speaking phobia using a single-session exposure therapy protocol previously shown to be efficacious but also associated with some ROF. Consistent with predictions, a post-treatment implicit measure of attitudes toward public speaking (the Personalized Implicit Association Test [PIAT]) predicted ROF at 1-month follow-up. These results suggest that change in the automatically activated attitude toward the phobic stimulus is an important goal of exposure therapy and that an implicit measure like the PIAT can provide a useful measure of such change by which to gauge the adequacy of exposure treatment and predict its long-term efficacy. PMID:23085186

Underpowered samples, false negatives, and unconscious learning.

PubMed

Vadillo, Miguel A; Konstantinidis, Emmanouil; Shanks, David R

2016-02-01

The scientific community has witnessed growing concern about the high rate of false positives and unreliable results within the psychological literature, but the harmful impact of false negatives has been largely ignored. False negatives are particularly concerning in research areas where demonstrating the absence of an effect is crucial, such as studies of unconscious or implicit processing. Research on implicit processes seeks evidence of above-chance performance on some implicit behavioral measure at the same time as chance-level performance (that is, a null result) on an explicit measure of awareness. A systematic review of 73 studies of contextual cuing, a popular implicit learning paradigm, involving 181 statistical analyses of awareness tests, reveals how underpowered studies can lead to failure to reject a false null hypothesis. Among the studies that reported sufficient information, the meta-analytic effect size across awareness tests was d z = 0.31 (95 % CI 0.24-0.37), showing that participants' learning in these experiments was conscious. The unusually large number of positive results in this literature cannot be explained by selective publication. Instead, our analyses demonstrate that these tests are typically insensitive and underpowered to detect medium to small, but true, effects in awareness tests. These findings challenge a widespread and theoretically important claim about the extent of unconscious human cognition.

Visual artificial grammar learning in dyslexia: A meta-analysis.

PubMed

van Witteloostuijn, Merel; Boersma, Paul; Wijnen, Frank; Rispens, Judith

2017-11-01

Literacy impairments in dyslexia have been hypothesized to be (partly) due to an implicit learning deficit. However, studies of implicit visual artificial grammar learning (AGL) have often yielded null results. The aim of this study is to weigh the evidence collected thus far by performing a meta-analysis of studies on implicit visual AGL in dyslexia. Thirteen studies were selected through a systematic literature search, representing data from 255 participants with dyslexia and 292 control participants (mean age range: 8.5-36.8 years old). If the 13 selected studies constitute a random sample, individuals with dyslexia perform worse on average than non-dyslexic individuals (average weighted effect size=0.46, 95% CI [0.14 … 0.77], p=0.008), with a larger effect in children than in adults (p=0.041; average weighted effect sizes 0.71 [sig.] versus 0.16 [non-sig.]). However, the presence of a publication bias indicates the existence of missing studies that may well null the effect. While the studies under investigation demonstrate that implicit visual AGL is impaired in dyslexia (more so in children than in adults, if in adults at all), the detected publication bias suggests that the effect might in fact be zero. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

(In)Congruence of implicit and explicit communal motives predicts the quality and stability of couple relationships.

PubMed

Hagemeyer, Birk; Neberich, Wiebke; Asendorpf, Jens B; Neyer, Franz J

2013-08-01

Previous research has shown that motive congruence, as observed in convergingly high or low scores on implicit and explicit motive measures, promotes well-being and health. Extending this individual perspective to the realm of couple relationships, the present investigation examined intra- and interpersonal effects of communal motive (in)congruence on relationship satisfaction and stability. The implicit partner-related need for communion, the explicit desire for closeness, and relationship satisfaction were assessed in a sample of 547 heterosexual couples aged 18 to 73 years. In a one-year follow-up study, information on relationship stability was obtained, and relationship satisfaction was reassessed. The researchers tested cross-sectional and longitudinal effects of motive (in)congruence by dyadic moderation analyses. Individuals scoring congruently high on both motives reported the highest relationship satisfaction in concurrence with motive assessment and 1 year later. In addition, motive incongruence predicted an increased risk of relationship breakup over 1 year. The results highlight the significance of both implicit and explicit motives for couple relationships. Motive incongruence was confirmed as a dispositional risk factor that so far has not been considered in couple research. Future research directions addressing potential mediators of the observed effects and potential moderators of motive (in)congruence are discussed. © 2012 Wiley Periodicals, Inc.

Assessing implicit models for nonpolar mean solvation forces: The importance of dispersion and volume terms

PubMed Central

Wagoner, Jason A.; Baker, Nathan A.

2006-01-01

Continuum solvation models provide appealing alternatives to explicit solvent methods because of their ability to reproduce solvation effects while alleviating the need for expensive sampling. Our previous work has demonstrated that Poisson-Boltzmann methods are capable of faithfully reproducing polar explicit solvent forces for dilute protein systems; however, the popular solvent-accessible surface area model was shown to be incapable of accurately describing nonpolar solvation forces at atomic-length scales. Therefore, alternate continuum methods are needed to reproduce nonpolar interactions at the atomic scale. In the present work, we address this issue by supplementing the solvent-accessible surface area model with additional volume and dispersion integral terms suggested by scaled particle models and Weeks–Chandler–Andersen theory, respectively. This more complete nonpolar implicit solvent model shows very good agreement with explicit solvent results and suggests that, although often overlooked, the inclusion of appropriate dispersion and volume terms are essential for an accurate implicit solvent description of atomic-scale nonpolar forces. PMID:16709675

Predicting hydration free energies with a hybrid QM/MM approach

PubMed Central

König, Gerhard; Pickard, Frank C.; Mei, Ye; Brooks, Bernard R.

2014-01-01

The correct representation of solute-water interactions is essential for the accurate simulation of most biological phenomena. Several highly accurate quantum methods are available to deal with solvation by using both implicit and explicit solvents. So far, however, most evaluations of those methods were based on a single conformation, which neglects solute entropy. Here, we present the first test of a novel approach to determine hydration free energies that uses molecular mechanics (MM) to sample phase space and quantum mechanics (QM) to evaluate the potential energies. Free energies are determined by using re-weighting with the Non-Boltzmann Bennett (NBB) method. In this context, the method is referred to as QM-NBB. Based on snapshots from MM sampling and accounting for their correct Boltzmann weight, it is possible to obtain hydration free energies that incorporate the effect of solute entropy. We evaluate the performance of several QM implicit solvent models, as well as explicit solvent QM/MM for the blind subset of the SAMPL4 hydration free energy challenge. While classical free energy simulations with molecular dynamics give root mean square deviations (RMSD) of 2.8 and 2.3 kcal/mol, the hybrid approach yields an improved RMSD of 1.6 kcal/mol. By selecting an appropriate functional and basis set, the RMSD can be reduced to 1 kcal/mol for calculations based on a single conformation. Results for a selected set of challenging molecules imply that this RMSD can be further reduced by using NBB to reweight MM trajectories with the SMD implicit solvent model. PMID:24504703

Using implicit association tests in age-heterogeneous samples: The importance of cognitive abilities and quad model processes.

PubMed

Wrzus, Cornelia; Egloff, Boris; Riediger, Michaela

2017-08-01

Implicit association tests (IATs) are increasingly used to indirectly assess people's traits, attitudes, or other characteristics. In addition to measuring traits or attitudes, IAT scores also reflect differences in cognitive abilities because scores are based on reaction times (RTs) and errors. As cognitive abilities change with age, questions arise concerning the usage and interpretation of IATs for people of different age. To address these questions, the current study examined how cognitive abilities and cognitive processes (i.e., quad model parameters) contribute to IAT results in a large age-heterogeneous sample. Participants (N = 549; 51% female) in an age-stratified sample (range = 12-88 years) completed different IATs and 2 tasks to assess cognitive processing speed and verbal ability. From the IAT data, D2-scores were computed based on RTs, and quad process parameters (activation of associations, overcoming bias, detection, guessing) were estimated from individual error rates. Substantial IAT scores and quad processes except guessing varied with age. Quad processes AC and D predicted D2-scores of the content-specific IAT. Importantly, the effects of cognitive abilities and quad processes on IAT scores were not significantly moderated by participants' age. These findings suggest that IATs seem suitable for age-heterogeneous studies from adolescence to old age when IATs are constructed and analyzed appropriately, for example with D-scores and process parameters. We offer further insight into how D-scoring controls for method effects in IATs and what IAT scores capture in addition to implicit representations of characteristics. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Peptoid conformational free energy landscapes from implicit-solvent molecular simulations in AMBER.

PubMed

Voelz, Vincent A; Dill, Ken A; Chorny, Ilya

2011-01-01

To test the accuracy of existing AMBER force field models in predicting peptoid conformation and dynamics, we simulated a set of model peptoid molecules recently examined by Butterfoss et al. (JACS 2009, 131, 16798-16807) using QM methods as well as three peptoid sequences with experimentally determined structures. We found that AMBER force fields, when used with a Generalized Born/Surface Area (GBSA) implicit solvation model, could accurately reproduce the peptoid torsional landscape as well as the major conformers of known peptoid structures. Enhanced sampling by replica exchange molecular dynamics (REMD) using temperatures from 300 to 800 K was used to sample over cis-trans isomerization barriers. Compared to (Nrch)5 and cyclo-octasarcosyl, the free energy of N-(2-nitro-3-hydroxyl phenyl)glycine-N-(phenyl)glycine has the most "foldable" free energy landscape, due to deep trans-amide minima dictated by N-aryl sidechains. For peptoids with (S)-N (1-phenylethyl) (Nspe) side chains, we observe a discrepancy in backbone dihedral propensities between molecular simulations and QM calculations, which may be due to force field effects or the inability to capture n --> n* interactions. For these residues, an empirical phi-angle biasing potential can "rescue" the backbone propensities seen in QM. This approach can serve as a general strategy for addressing force fields without resorting to a complete reparameterization. Overall, this study demonstrates the utility of implicit-solvent REMD simulations for efficient sampling to predict peptoid conformational landscapes, providing a potential tool for first-principles design of sequences with specific folding properties.

Implicit theories of writing and their impact on students' response to a SRSD intervention.

PubMed

Limpo, Teresa; Alves, Rui A

2014-12-01

In the field of intelligence research, it has been shown that some people conceive intelligence as a fixed trait that cannot be changed (entity beliefs), whereas others conceive it as a malleable trait that can be developed (incremental beliefs). What about writing? Do people hold similar implicit theories about the nature of their writing ability? Furthermore, are these beliefs likely to influence students' response to a writing intervention? We aimed to develop a scale to measure students' implicit theories of writing (pilot study) and to test whether these beliefs influence strategy-instruction effectiveness (intervention study). In the pilot and intervention studies participated, respectively, 128 and 192 students (Grades 5-6). Based on existing instruments that measure self-theories of intelligence, we developed the Implicit Theories of Writing (ITW) scale that was tested with the pilot sample. In the intervention study, 109 students received planning instruction based on the self-regulated strategy development model, whereas 83 students received standard writing instruction. Students were evaluated before, in the middle, and after instruction. ITW's validity was supported by piloting results and their successful cross-validation in the intervention study. In this, intervention students wrote longer and better texts than control students. Moreover, latent growth curve modelling showed that the more the intervention students conceived writing as a malleable skill, the more the quality of their texts improved. This research is of educational relevance because it provides a measure to evaluate students' implicit theories of writing and shows their impact on response to intervention. © 2014 The British Psychological Society.

The Brief Death Implicit Association Test: Scoring recommendations, reliability, validity, and comparisons with the Death Implicit Association Test.

PubMed

Millner, Alexander J; Coppersmith, Daniel D L; Teachman, Bethany A; Nock, Matthew K

2018-05-21

Assessing suicidal thoughts and behaviors is difficult because at-risk individuals often fail to provide honest or accurate accounts of their suicidal thoughts or intentions. Research has shown that the Death Implicit Association Test (D-IAT), a behavioral test that measures implicit (i.e., outside of conscious control) associations between oneself and death concepts, can differentiate among people with different suicidal histories, such as those with different severity or recency of suicidal behaviors. We report here on the development and evaluation of a shorter and simpler version of the D-IAT called the Death Brief Implicit Association Test (D-BIAT). We recruited large (ns > 1,500) samples of participants to complete the original D-IAT and shorter D-BIAT via a public web-based platform and evaluated different scoring approaches, assessed the reliability and validity of the D-BIAT and compared it with the D-IAT. We found that the D-BIAT was reliable, provided significant group differences with effect sizes on par with the D-IAT, as well as similarly sized classification metrics (i.e., receiver operator characteristics). Although the D-IAT was nonsignificantly better on most outcomes, the D-BIAT is 1-1[1/2] minutes shorter and provided larger effect sizes for distinguishing between past year and lifetime attempters. Thus, there is a trade-off between administration time and improved outcomes associated with increased data. The D-BIAT should be considered for use where time or participant burden needs to be minimized, such as in clinical settings. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Protein-ligand docking using FFT based sampling: D3R case study.

PubMed

Padhorny, Dzmitry; Hall, David R; Mirzaei, Hanieh; Mamonov, Artem B; Moghadasi, Mohammad; Alekseenko, Andrey; Beglov, Dmitri; Kozakov, Dima

2018-01-01

Fast Fourier transform (FFT) based approaches have been successful in application to modeling of relatively rigid protein-protein complexes. Recently, we have been able to adapt the FFT methodology to treatment of flexible protein-peptide interactions. Here, we report our latest attempt to expand the capabilities of the FFT approach to treatment of flexible protein-ligand interactions in application to the D3R PL-2016-1 challenge. Based on the D3R assessment, our FFT approach in conjunction with Monte Carlo minimization off-grid refinement was among the top performing methods in the challenge. The potential advantage of our method is its ability to globally sample the protein-ligand interaction landscape, which will be explored in further applications.

Exploring transition pathway and free-energy profile of large-scale protein conformational change by combining normal mode analysis and umbrella sampling molecular dynamics.

PubMed

Wang, Jinan; Shao, Qiang; Xu, Zhijian; Liu, Yingtao; Yang, Zhuo; Cossins, Benjamin P; Jiang, Hualiang; Chen, Kaixian; Shi, Jiye; Zhu, Weiliang

2014-01-09

Large-scale conformational changes of proteins are usually associated with the binding of ligands. Because the conformational changes are often related to the biological functions of proteins, understanding the molecular mechanisms of these motions and the effects of ligand binding becomes very necessary. In the present study, we use the combination of normal-mode analysis and umbrella sampling molecular dynamics simulation to delineate the atomically detailed conformational transition pathways and the associated free-energy landscapes for three well-known protein systems, viz., adenylate kinase (AdK), calmodulin (CaM), and p38α kinase in the absence and presence of respective ligands. For each protein under study, the transient conformations along the conformational transition pathway and thermodynamic observables are in agreement with experimentally and computationally determined ones. The calculated free-energy profiles reveal that AdK and CaM are intrinsically flexible in structures without obvious energy barrier, and their ligand binding shifts the equilibrium from the ligand-free to ligand-bound conformation (population shift mechanism). In contrast, the ligand binding to p38α leads to a large change in free-energy barrier (ΔΔG ≈ 7 kcal/mol), promoting the transition from DFG-in to DFG-out conformation (induced fit mechanism). Moreover, the effect of the protonation of D168 on the conformational change of p38α is also studied, which reduces the free-energy difference between the two functional states of p38α and thus further facilitates the conformational interconversion. Therefore, the present study suggests that the detailed mechanism of ligand binding and the associated conformational transition is not uniform for all kinds of proteins but correlated to their respective biological functions.

ForceGen 3D structure and conformer generation: from small lead-like molecules to macrocyclic drugs

NASA Astrophysics Data System (ADS)

Cleves, Ann E.; Jain, Ajay N.

2017-05-01

We introduce the ForceGen method for 3D structure generation and conformer elaboration of drug-like small molecules. ForceGen is novel, avoiding use of distance geometry, molecular templates, or simulation-oriented stochastic sampling. The method is primarily driven by the molecular force field, implemented using an extension of MMFF94s and a partial charge estimator based on electronegativity-equalization. The force field is coupled to algorithms for direct sampling of realistic physical movements made by small molecules. Results are presented on a standard benchmark from the Cambridge Crystallographic Database of 480 drug-like small molecules, including full structure generation from SMILES strings. Reproduction of protein-bound crystallographic ligand poses is demonstrated on four carefully curated data sets: the ConfGen Set (667 ligands), the PINC cross-docking benchmark (1062 ligands), a large set of macrocyclic ligands (182 total with typical ring sizes of 12-23 atoms), and a commonly used benchmark for evaluating macrocycle conformer generation (30 ligands total). Results compare favorably to alternative methods, and performance on macrocyclic compounds approaches that observed on non-macrocycles while yielding a roughly 100-fold speed improvement over alternative MD-based methods with comparable performance.

A web server for analysis, comparison and prediction of protein ligand binding sites.

PubMed

Singh, Harinder; Srivastava, Hemant Kumar; Raghava, Gajendra P S

2016-03-25

One of the major challenges in the field of system biology is to understand the interaction between a wide range of proteins and ligands. In the past, methods have been developed for predicting binding sites in a protein for a limited number of ligands. In order to address this problem, we developed a web server named 'LPIcom' to facilitate users in understanding protein-ligand interaction. Analysis, comparison and prediction modules are available in the "LPIcom' server to predict protein-ligand interacting residues for 824 ligands. Each ligand must have at least 30 protein binding sites in PDB. Analysis module of the server can identify residues preferred in interaction and binding motif for a given ligand; for example residues glycine, lysine and arginine are preferred in ATP binding sites. Comparison module of the server allows comparing protein-binding sites of multiple ligands to understand the similarity between ligands based on their binding site. This module indicates that ATP, ADP and GTP ligands are in the same cluster and thus their binding sites or interacting residues exhibit a high level of similarity. Propensity-based prediction module has been developed for predicting ligand-interacting residues in a protein for more than 800 ligands. In addition, a number of web-based tools have been integrated to facilitate users in creating web logo and two-sample between ligand interacting and non-interacting residues. In summary, this manuscript presents a web-server for analysis of ligand interacting residue. This server is available for public use from URL http://crdd.osdd.net/raghava/lpicom .

Simple method to assess stability of immobilized peptide ligands against proteases.

PubMed

Giudicessi, Silvana L; Salum, María L; Saavedra, Soledad L; Martínez-Ceron, María C; Cascone, Osvaldo; Erra-Balsells, Rosa; Camperi, Silvia A

2017-09-01

Although peptides are used as affinity chromatography ligands, they could be digested by proteases. Usually, peptide stability is evaluated in solution, which differs from the resin-bounded peptide behavior. Furthermore, the study of the degradation products requires purification steps before analysis. Here, we describe an easy method to assess immobilized peptide stability. Sample peptides were synthesized on hydroxymethylbenzamide-ChemMatrix resin. Peptidyl-resin beads were then incubated with solutions containing proteases. Peptides were detached from the solid support with ammonia vapor and analyzed by matrix-assisted laser desorption/ionization and electrospray ionization mass spectrometry, allowing the detection of the whole peptides as well as their C-terminal degradation products. The method allowed a fast evaluation of peptide ligand stability in solid phase towards proteases that may be present in the crude sample before their use as ligands in affinity chromatography. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.

An investigation of associations between clinicians' ethnic or racial bias and hypertension treatment, medication adherence and blood pressure control.

PubMed

Blair, Irene V; Steiner, John F; Hanratty, Rebecca; Price, David W; Fairclough, Diane L; Daugherty, Stacie L; Bronsert, Michael; Magid, David J; Havranek, Edward P

2014-07-01

Few studies have directly investigated the association of clinicians' implicit (unconscious) bias with health care disparities in clinical settings. To determine if clinicians' implicit ethnic or racial bias is associated with processes and outcomes of treatment for hypertension among black and Latino patients, relative to white patients. Primary care clinicians completed Implicit Association Tests of ethnic and racial bias. Electronic medical records were queried for a stratified, random sample of the clinicians' black, Latino and white patients to assess treatment intensification, adherence and control of hypertension. Multilevel random coefficient models assessed the associations between clinicians' implicit biases and ethnic or racial differences in hypertension care and outcomes. Standard measures of treatment intensification and medication adherence were calculated from pharmacy refills. Hypertension control was assessed by the percentage of time that patients met blood pressure goals recorded during primary care visits. One hundred and thirty-eight primary care clinicians and 4,794 patients with hypertension participated. Black patients received equivalent treatment intensification, but had lower medication adherence and worse hypertension control than white patients; Latino patients received equivalent treatment intensification and had similar hypertension control, but lower medication adherence than white patients. Differences in treatment intensification, medication adherence and hypertension control were unrelated to clinician implicit bias for black patients (P = 0.85, P = 0.06 and P = 0.31, respectively) and for Latino patients (P = 0.55, P = 0.40 and P = 0.79, respectively). An increase in clinician bias from average to strong was associated with a relative change of less than 5 % in all outcomes for black and Latino patients. Implicit bias did not affect clinicians' provision of care to their minority patients, nor did it affect the patients' outcomes. The identification of health care contexts in which bias does not impact outcomes can assist both patients and clinicians in their efforts to build trust and partnership.

Attempted Training of Alcohol Approach and Drinking Identity Associations in US Undergraduate Drinkers: Null Results from Two Studies

PubMed Central

Lindgren, Kristen P.; Wiers, Reinout W.; Teachman, Bethany A.; Gasser, Melissa L.; Westgate, Erin C.; Cousijn, Janna; Enkema, Matthew C.; Neighbors, Clayton

2015-01-01

There is preliminary evidence that approach avoid training can shift implicit alcohol associations and improve treatment outcomes. We sought to replicate and extend those findings in US undergraduate social drinkers (Study 1) and at-risk drinkers (Study 2). Three adaptations of the approach avoid task (AAT) were tested. The first adaptation – the approach avoid training – was a replication and targeted implicit alcohol approach associations. The remaining two adaptations – the general identity and personalized identity trainings – targeted implicit drinking identity associations, which are robust predictors of hazardous drinking in US undergraduates. Study 1 included 300 undergraduate social drinkers. They were randomly assigned to real or sham training conditions for one of the three training adaptations, and completed two training sessions, spaced one week apart. Study 2 included 288 undergraduates at risk for alcohol use disorders. The same training procedures were used, but the two training sessions occurred within a single week. Results were not as expected. Across both studies, the approach avoid training yielded no evidence of training effects on implicit alcohol associations or alcohol outcomes. The general identity training also yielded no evidence of training effects on implicit alcohol associations or alcohol outcomes with one exception; individuals who completed real training demonstrated no changes in drinking refusal self-efficacy whereas individuals who completed sham training had reductions in self-efficacy. Finally, across both studies, the personalized identity training yielded no evidence of training effects on implicit alcohol associations or alcohol outcomes. Despite having relatively large samples and using a well-validated training task, study results indicated all three training adaptations were ineffective at this dose in US undergraduates. These findings are important because training studies are costly and labor-intensive. Future research may benefit from focusing on more severe populations, pairing training with other interventions, increasing training dose, and increasing gamification of training tasks. PMID:26241316

Non-steroidal anti-inflammatory drug naproxen destabilizes Aβ amyloid fibrils: A molecular dynamics investigation

PubMed Central

Takeda, Takako; Kumar, Rashmi; Raman, E. Prabhu; Klimov, Dmitri K.

2010-01-01

Using implicit solvent model and replica exchange molecular dynamics we examine the propensity of non-steroidal anti-inflammatory drug, naproxen, to interfere with Aβ fibril growth. We also compare the anti-aggregation propensity of naproxen with that of ibuprofen. Naproxen anti-aggregation effect is influenced by two factors. Similar to ibuprofen, naproxen destabilizes binding of incoming Aβ peptides to the fibril due to direct competition between the ligands and the peptides for the same binding location on the fibril surface (the edge). However, in contrast to ibuprofen naproxen binding also alters the conformational ensemble of Aβ monomers by promoting β-structure. The second factor weakens naproxen anti-aggregation effect. These findings appear to explain the experimental observations, according to which naproxen binds to Aβ fibril with higher affinity than ibuprofen, yet produces weaker anti-aggregation action. PMID:20979356

Implicit particle filtering for equations with partial noise and application to geomagnetic data assimilation

NASA Astrophysics Data System (ADS)

Morzfeld, M.; Atkins, E.; Chorin, A. J.

2011-12-01

The task in data assimilation is to identify the state of a system from an uncertain model supplemented by a stream of incomplete and noisy data. The model is typically given in form of a discretization of an Ito stochastic differential equation (SDE), x(n+1) = R(x(n))+ G W(n), where x is an m-dimensional vector and n=0,1,2,.... The m-dimensional vector function R and the m x m matrix G depend on the SDE as well as on the discretization scheme, and W is an m-dimensional vector whose elements are independent standard normal variates. The data are y(n) = h(x(n))+QV(n) where h is a k-dimensional vector function, Q is a k x k matrix and V is a vector whose components are independent standard normal variates. One can use statistics of the conditional probability density (pdf) of the state given the observations, p(n+1)=p(x(n+1)|y(1), ... , y(n+1)), to identify the state x(n+1). Particle filters approximate p(n+1) by sequential Monte Carlo and rely on the recursive formulation of the target pdf, p(n+1)∝p(x(n+1)|x(n)) p(y(n+1)|x(n+1)). The pdf p(x(n+1)|x(n)) can be read off of the model equations to be a Gaussian with mean R(x(n)) and covariance matrix Σ = GG^T, where the T denotes a transposed; the pdf p(y(n+1)|x(n+1)) is a Gaussian with mean h(x(n+1)) and covariance QQ^T. In a sampling-importance-resampling (SIR) filter one samples new values for the particles from a prior pdf and then one weighs these samples with weights determined by the observations, to yield an approximation to p(n+1). Such weighting schemes often yield small weights for many of the particles. Implicit particle filtering overcomes this problem by using the observations to generate the particles, thus focusing attention on regions of large probability. A suitable algebraic equation that depends on the model and the observations is constructed for each particle, and its solution yields high probability samples of p(n+1). In the current formulation of the implicit particle filter, the state covariance matrix Σ is assumed to be non-singular. In the present work we consider the case where the covariance Σ is singular. This happens in particular when the noise is spatially smooth and can be represented by a small number of Fourier coefficients, as is often the case in geophysical applications. We derive an implicit filter for this problem and show that it is very efficient, because the filter operates in a space whose dimension is the rank of Σ, rather than the full model dimension. We compare the implicit filter to SIR, to the Ensemble Kalman Filter and to variational methods, and also study how information from data is propagated from observed to unobserved variables. We illustrate the theory on two coupled nonlinear PDE's in one space dimension that have been used as a test-bed for geomagnetic data assimilation. We observe that the implicit filter gives good results with few (2-10) particles, while SIR requires thousands of particles for similar accuracy. We also find lower limits to the accuracy of the filter's reconstruction as a function of data availability.

A Four-Hour Yeast Bioassay for the Direct Measure of Estrogenic Activity in Wastewater without Sample Extraction, Concentration, or Sterilization

PubMed Central

Balsiger, Heather A.; de la Torre, Roberto; Lee, Wen-Yee; Cox, Marc B.

2010-01-01

The assay described here represents an improved yeast bioassay that provides a rapid yet sensitive screening method for EDCs with very little hands-on time and without the need for sample preparation. Traditional receptor-mediated reporter assays in yeast were performed twelve to twenty four hours after ligand addition, used colorimetric substrates, and, in many cases, required high, non-physiological concentrations of ligand. With the advent of new chemiluminescent substrates a ligand-induced signal can be detected within thirty minutes using high picomolar to low nanomolar concentrations of estrogen. As a result of the sensitivity (EC50 for estradiol is ~ 0.7 nM) and the very short assay time (2-4 hours) environmental water samples can typically be assayed directly without sterilization, extraction, and concentration. Thus, these assays represent rapid and sensitive approaches for determining the presence of contaminants in environmental samples. As proof of principle, we directly assayed wastewater influent and effluent taken from a wastewater treatment plant in the El Paso, TX area for the presence of estrogenic activity. The data obtained in the four-hour yeast bioassay directly correlated with GC-mass spectrometry analysis of these same water samples. PMID:20074779

Determination of the total concentration and speciation of metal ions in river, estuarine and seawater samples.

PubMed

Alberti, Giancarla; Biesuz, Raffaela; Pesavento, Maria

2008-12-01

Different natural water samples were investigated to determine the total concentration and the distribution of species for Cu(II), Pb(II), Al(III) and U(VI). The proposed method, named resin titration (RT), was developed in our laboratory to investigate the distribution of species for metal ions in complex matrices. It is a competition method, in which a complexing resin competes with natural ligands present in the sample to combine with the metal ions. In the present paper, river, estuarine and seawater samples, collected during a cruise in Adriatic Sea, were investigated. For each sample, two RTs were performed, using different complexing resins: the iminodiacetic Chelex 100 and the carboxylic Amberlite CG50. In this way, it was possible to detect different class of ligands. Satisfactory results have been obtained and are commented on critically. They were summarized by principal component analysis (PCA) and the correlations with physicochemical parameters allowed one to follow the evolution of the metals along the considered transect. It should be pointed out that, according to our findings, the ligands responsible for metal ions complexation are not the major components of the water system, since they form considerably weaker complexes.

The identification of implicit theories in domestic violence perpetrators.

PubMed

Dempsey, Bernadette; Day, Andrew

2011-05-01

An understanding of how the beliefs of domestically violent offenders might influence their abusive behavior is central to the development and delivery of any intervention program that aims to reduce the risk of further violence against women and children. This article reports the results of a preliminary investigation into the core beliefs of a sample of domestically violent men. Three major themes emerged from an analysis of the accounts of their violence, which were understood in relation to three implicit theories that participants held about themselves, their relationships, and the world. These are discussed in terms of previous studies of offender cognition, how domestic violence programs might be conceptualized, and their implications for practice.

Molecular simulations of assembly of functionalized spherical nanoparticles

NASA Astrophysics Data System (ADS)

Seifpour, Arezou

Precise assembly of nanoparticles is crucial for creating spatially engineered materials that can be used for photonics, photovoltaic, and metamaterials applications. One way to control nanoparticle assembly is by functionalizing the nanoparticle with ligands, such as polymers, DNA, and proteins, that can manipulate the interactions between the nanoparticles in the medium the particles are placed in. This thesis research aims to design ligands to provide a new route to the programmable assembly of nanoparticles. We first investigate using Monte Carlo simulation the effect of copolymer ligands on nanoparticle assembly. We first study a single nanoparticle grafted with many copolymer chains to understand how monomer sequence (e.g. alternating ABAB, or diblock AxBx) and chemistry of the copolymers affect the grafted chain conformation at various particle diameters, grafting densities, copolymer chain lengths, and monomer-monomer interactions in an implicit small molecule solvent. We find that the size of the grafted chain varies non-monotonically with increasing blockiness of the monomer sequence for a small particle diameter. From this first study, we selected the two sequences with the most different chain conformations---alternating and diblock---and studied the effect of the sequence and a range of monomer chemistries of the copolymer on the characteristics of assembly of multiple copolymer-functionalized nanoparticles. We find that the alternating sequence produces nanoclusters that are relatively isotropic, whereas diblock sequence tends to form anisotropic structures that are smaller and more compact when the block closer to the surface is attractive and larger loosely held together clusters when the outer block is attractive. Next, we conduct molecular dynamics simulations to study the effect of DNA ligands on nanoparticle assembly. Specifically we investigate the effect of grafted DNA strand composition (e.g. G/C content, placement and sequence) and bidispersity in DNA strand lengths on the thermodynamics and structure of assembly of functionalized nanoparticles. We find that higher G/C content increases cluster dissociation temperature for smaller particles. Placement of G/C block inward along the strand decreases number of neighbors within the assembled cluster. Finally, increased bidispersity in DNA strand lengths leads a distribution of inter-particle distances in the assembled cluster.

Development of Novel Method for Rapid Extract of Radionuclides from Solution Using Polymer Ligand Film

NASA Astrophysics Data System (ADS)

Rim, Jung H.

Accurate and fast determination of the activity of radionuclides in a sample is critical for nuclear forensics and emergency response. Radioanalytical techniques are well established for radionuclides measurement, however, they are slow and labor intensive, requiring extensive radiochemical separations and purification prior to analysis. With these limitations of current methods, there is great interest for a new technique to rapidly process samples. This dissertation describes a new analyte extraction medium called Polymer Ligand Film (PLF) developed to rapidly extract radionuclides. Polymer Ligand Film is a polymer medium with ligands incorporated in its matrix that selectively and rapidly extract analytes from a solution. The main focus of the new technique is to shorten and simplify the procedure necessary to chemically isolate radionuclides for determination by alpha spectrometry or beta counting. Five different ligands were tested for plutonium extraction: bis(2-ethylhexyl) methanediphosphonic acid (H2DEH[MDP]), di(2-ethyl hexyl) phosphoric acid (HDEHP), trialkyl methylammonium chloride (Aliquat-336), 4,4'(5')-di-t-butylcyclohexano 18-crown-6 (DtBuCH18C6), and 2-ethylhexyl 2-ethylhexylphosphonic acid (HEH[EHP]). The ligands that were effective for plutonium extraction further studied for uranium extraction. The plutonium recovery by PLFs has shown dependency on nitric acid concentration and ligand to total mass ratio. H2DEH[MDP] PLFs performed best with 1:10 and 1:20 ratio PLFs. 50.44% and 47.61% of plutonium were extracted on the surface of PLFs with 1M nitric acid for 1:10 and 1:20 PLF, respectively. HDEHP PLF provided the best combination of alpha spectroscopy resolution and plutonium recovery with 1:5 PLF when used with 0.1M nitric acid. The overall analyte recovery was lower than electrodeposited samples, which typically has recovery above 80%. However, PLF is designed to be a rapid field deployable screening technique and consistency is more important than recovery. PLFs were also tested using blind quality control samples and the activities were accurately measured. It is important to point out that PLFs were consistently susceptible to analytes penetrating and depositing below the surface. The internal radiation within the body of PLF is mostly contained and did not cause excessive self-attenuation and peak broadening in alpha spectroscopy. The analyte penetration issue was beneficial in the destructive analysis. H2DEH[MDP] PLF was tested with environmental samples to fully understand the capabilities and limitations of the PLF in relevant environments. The extraction system was very effective in extracting plutonium from environmental water collected from Mortandad Canyon at Los Alamos National Laboratory with minimal sample processing. Soil samples were tougher to process than the water samples. Analytes were first leached from the soil matrixes using nitric acid before processing with PLF. This approach had a limitation in extracting plutonium using PLF. The soil samples from Mortandad Canyon, which are about 1% iron by weight, were effectively processed with the PLF system. Even with certain limitations of the PLF extraction system, this technique was able to considerably decrease the sample analysis time. The entire environmental sample was analyzed within one to two days. The decrease in time can be attributed to the fact that PLF is replacing column chromatography and electrodeposition with a single step for preparing alpha spectrometry samples. The two-step process of column chromatography and electrodeposition takes a couple days to a week to complete depending on the sample. The decrease in time and the simplified procedure make this technique a unique solution for application to nuclear forensics and emergency response. A large number of samples can be quickly analyzed and selective samples can be further analyzed with more sensitive techniques based on the initial data. The deployment of a PLF system as a screening method will greatly reduce a total analysis time required to gain meaningful isotopic data for the nuclear forensics application. (Abstract shortened by UMI.)

Flexible CDOCKER: Development and application of a pseudo-explicit structure-based docking method within CHARMM

PubMed Central

Gagnon, Jessica K.; Law, Sean M.; Brooks, Charles L.

2016-01-01

Protein-ligand docking is a commonly used method for lead identification and refinement. While traditional structure-based docking methods represent the receptor as a rigid body, recent developments have been moving toward the inclusion of protein flexibility. Proteins exist in an inter-converting ensemble of conformational states, but effectively and efficiently searching the conformational space available to both the receptor and ligand remains a well-appreciated computational challenge. To this end, we have developed the Flexible CDOCKER method as an extension of the family of complete docking solutions available within CHARMM. This method integrates atomically detailed side chain flexibility with grid-based docking methods, maintaining efficiency while allowing the protein and ligand configurations to explore their conformational space simultaneously. This is in contrast to existing approaches that use induced-fit like sampling, such as Glide or Autodock, where the protein or the ligand space is sampled independently in an iterative fashion. Presented here are developments to the CHARMM docking methodology to incorporate receptor flexibility and improvements to the sampling protocol as demonstrated with re-docking trials on a subset of the CCDC/Astex set. These developments within CDOCKER achieve docking accuracy competitive with or exceeding the performance of other widely utilized docking programs. PMID:26691274

Flexible CDOCKER: Development and application of a pseudo-explicit structure-based docking method within CHARMM.

PubMed

Gagnon, Jessica K; Law, Sean M; Brooks, Charles L

2016-03-30

Protein-ligand docking is a commonly used method for lead identification and refinement. While traditional structure-based docking methods represent the receptor as a rigid body, recent developments have been moving toward the inclusion of protein flexibility. Proteins exist in an interconverting ensemble of conformational states, but effectively and efficiently searching the conformational space available to both the receptor and ligand remains a well-appreciated computational challenge. To this end, we have developed the Flexible CDOCKER method as an extension of the family of complete docking solutions available within CHARMM. This method integrates atomically detailed side chain flexibility with grid-based docking methods, maintaining efficiency while allowing the protein and ligand configurations to explore their conformational space simultaneously. This is in contrast to existing approaches that use induced-fit like sampling, such as Glide or Autodock, where the protein or the ligand space is sampled independently in an iterative fashion. Presented here are developments to the CHARMM docking methodology to incorporate receptor flexibility and improvements to the sampling protocol as demonstrated with re-docking trials on a subset of the CCDC/Astex set. These developments within CDOCKER achieve docking accuracy competitive with or exceeding the performance of other widely utilized docking programs. © 2015 Wiley Periodicals, Inc.

The role of intramolecular nonbonded interaction and angle sampling in single-step free energy perturbation

NASA Astrophysics Data System (ADS)

Chiang, Ying-Chih; Pang, Yui Tik; Wang, Yi

2016-12-01

Single-step free energy perturbation (sFEP) has often been proposed as an efficient tool for a quick free energy scan due to its straightforward protocol and the ability to recycle an existing molecular dynamics trajectory for free energy calculations. Although sFEP is expected to fail when the sampling of a system is inefficient, it is often expected to hold for an alchemical transformation between ligands with a moderate difference in their sizes, e.g., transforming a benzene into an ethylbenzene. Yet, exceptions were observed in calculations for anisole and methylaniline, which have similar physical sizes as ethylbenzene. In this study, we show that such exceptions arise from the sampling inefficiency on an unexpected rigid degree of freedom, namely, the bond angle θ. The distributions of θ differ dramatically between two end states of a sFEP calculation, i.e., the conformation of the ligand changes significantly during the alchemical transformation process. Our investigation also reveals the interrelation between the ligand conformation and the intramolecular nonbonded interactions. This knowledge suggests a best combination of the ghost ligand potential and the dual topology setting, which improves the accuracy in a single reference sFEP calculation by bringing down its error from around 5kBT to kBT.

Influence of the membrane lipophilic environment on the structure and on the substrate access/egress routes of the human aromatase enzyme. A computational study.

PubMed

Sgrignani, Jacopo; Magistrato, Alessandra

2012-06-25

Human aromatase (HA), an enzyme located on the membrane of the endoplasmatic reticulum, is of crucial biological importance in the biosynthesis of estrogens. High levels of estrogens are related with important pathologies, conferring to HA a key role as a pharmacological target. In this study we provide, for the first time, an atomistic model of HA embedded on a membrane model to understand the influence of the membrane lipophilic environment on the structural and dynamical properties of HA and on the access/egress pathways of the substrate (androstenedione, ASD) and of the oxygen molecule (involved in the enzymatic process) into/from the HA active site. To this end we used several computational techniques such as force field-based molecular dynamics (MD) simulations, Random Expulsion MD, Steered MD, and Implicit Ligand Sampling. Our results show that the membrane anchoring does not markedly affect the structural properties and the flexibility of the protein, but they clearly point out that the membrane has a marked effect on the access/egress routes of the reactants, stabilizing the formation of different channels for both ASD and O(2) with respect to those observed in pure water solution. Due to the importance of HA in medicine and since access/egress channels may influence its substrate selectivity, a detailed understanding of the role of the membrane in shaping these channels may be of valuable help in drug design.

Measuring implicit attitudes: A positive framing bias flaw in the Implicit Relational Assessment Procedure (IRAP).

PubMed

O'Shea, Brian; Watson, Derrick G; Brown, Gordon D A

2016-02-01

How can implicit attitudes best be measured? The Implicit Relational Assessment Procedure (IRAP), unlike the Implicit Association Test (IAT), claims to measure absolute, not just relative, implicit attitudes. In the IRAP, participants make congruent (Fat Person-Active: false; Fat Person-Unhealthy: true) or incongruent (Fat Person-Active: true; Fat Person-Unhealthy: false) responses in different blocks of trials. IRAP experiments have reported positive or neutral implicit attitudes (e.g., neutral attitudes toward fat people) in cases in which negative attitudes are normally found on explicit or other implicit measures. It was hypothesized that these results might reflect a positive framing bias (PFB) that occurs when participants complete the IRAP. Implicit attitudes toward categories with varying prior associations (nonwords, social systems, flowers and insects, thin and fat people) were measured. Three conditions (standard, positive framing, and negative framing) were used to measure whether framing influenced estimates of implicit attitudes. It was found that IRAP scores were influenced by how the task was framed to the participants, that the framing effect was modulated by the strength of prior stimulus associations, and that a default PFB led to an overestimation of positive implicit attitudes when measured by the IRAP. Overall, the findings question the validity of the IRAP as a tool for the measurement of absolute implicit attitudes. A new tool (Simple Implicit Procedure:SIP) for measuring absolute, not just relative, implicit attitudes is proposed. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

A Freeze Substitution Fixation-Based Gold Enlarging Technique for EM Studies of Endocytosed Nanogold-Labeled Molecules

PubMed Central

He, Wanzhong; Kivork, Christine; Machinani, Suman; Morphew, Mary K.; Gail, Anna M.; Tesar, Devin B.; Tiangco, Noreen E.; McIntosh, J. Richard; Bjorkman, Pamela J.

2007-01-01

We have developed methods to locate individual ligands that can be used for electron microscopy studies of dynamic events during endocytosis and subsequent intracellular trafficking. The methods are based on enlargement of 1.4 nm Nanogold attached to an endocytosed ligand. Nanogold, a small label that does not induce misdirection of ligand-receptor complexes, is ideal for labeling ligands endocytosed by live cells, but is too small to be routinely located in cells by electron microscopy. Traditional pre-embedding enhancement protocols to enlarge Nanogold are not compatible with high pressure freezing/freeze substitution fixation (HPF/FSF), the most accurate method to preserve ultrastructure and dynamic events during trafficking. We have developed an improved enhancement procedure for chemically-fixed samples that reduced autonucleation, and a new pre-embedding gold-enlarging technique for HPF/FSF samples that preserved contrast and ultrastructure and can be used for high-resolution tomography. We evaluated our methods using labeled Fc as a ligand for the neonatal Fc receptor. Attachment of Nanogold to Fc did not interfere with receptor binding or uptake, and gold-labeled Fc could be specifically enlarged to allow identification in 2D projections and in tomograms. These methods should be broadly applicable to many endocytosis and transcytosis studies. PMID:17723309

Toward an Enhanced Sampling Molecular Dynamics Method for Studying Ligand-Induced Conformational Changes in Proteins.

PubMed

Andersen, Ole Juul; Grouleff, Julie; Needham, Perri; Walker, Ross C; Jensen, Frank

2015-11-19

Current enhanced sampling molecular dynamics methods for studying large conformational changes in proteins suffer from certain limitations. These include, among others, the need for user defined collective variables, the prerequisite of both start and end point structures of the conformational change, and the need for a priori knowledge of the amount by which to boost specific parts of the potential. In this paper, a framework is proposed for a molecular dynamics method for studying ligand-induced conformational changes, in which the nonbonded interactions between the ligand and the protein are used to calculate a biasing force. The method requires only a single input structure, and does not entail the use of collective variables. We provide a proof-of-concept for accelerating conformational changes in three simple test molecules, as well as promising results for two proteins known to undergo domain closure upon ligand binding. For the ribose-binding protein, backbone root-mean-square deviations as low as 0.75 Å compared to the crystal structure of the closed conformation are obtained within 50 ns simulations, whereas no domain closures are observed in unbiased simulations. A skewed closed structure is obtained for the glutamine-binding protein at high bias values, indicating that specific protein-ligand interactions might suppress important protein-protein interactions.

Structure refinement of membrane proteins via molecular dynamics simulations.

PubMed

Dutagaci, Bercem; Heo, Lim; Feig, Michael

2018-07-01

A refinement protocol based on physics-based techniques established for water soluble proteins is tested for membrane protein structures. Initial structures were generated by homology modeling and sampled via molecular dynamics simulations in explicit lipid bilayer and aqueous solvent systems. Snapshots from the simulations were selected based on scoring with either knowledge-based or implicit membrane-based scoring functions and averaged to obtain refined models. The protocol resulted in consistent and significant refinement of the membrane protein structures similar to the performance of refinement methods for soluble proteins. Refinement success was similar between sampling in the presence of lipid bilayers and aqueous solvent but the presence of lipid bilayers may benefit the improvement of lipid-facing residues. Scoring with knowledge-based functions (DFIRE and RWplus) was found to be as good as scoring using implicit membrane-based scoring functions suggesting that differences in internal packing is more important than orientations relative to the membrane during the refinement of membrane protein homology models. © 2018 Wiley Periodicals, Inc.

Increasing the sampling efficiency of protein conformational transition using velocity-scaling optimized hybrid explicit/implicit solvent REMD simulation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yu, Yuqi; Wang, Jinan; Shao, Qiang, E-mail: qshao@mail.shcnc.ac.cn, E-mail: Jiye.Shi@ucb.com, E-mail: wlzhu@mail.shcnc.ac.cn

2015-03-28

The application of temperature replica exchange molecular dynamics (REMD) simulation on protein motion is limited by its huge requirement of computational resource, particularly when explicit solvent model is implemented. In the previous study, we developed a velocity-scaling optimized hybrid explicit/implicit solvent REMD method with the hope to reduce the temperature (replica) number on the premise of maintaining high sampling efficiency. In this study, we utilized this method to characterize and energetically identify the conformational transition pathway of a protein model, the N-terminal domain of calmodulin. In comparison to the standard explicit solvent REMD simulation, the hybrid REMD is much lessmore » computationally expensive but, meanwhile, gives accurate evaluation of the structural and thermodynamic properties of the conformational transition which are in well agreement with the standard REMD simulation. Therefore, the hybrid REMD could highly increase the computational efficiency and thus expand the application of REMD simulation to larger-size protein systems.« less

Implicit depression and hopelessness in remitted depressed individuals.

PubMed

Meites, Tiffany M; Deveney, Christen M; Steele, Katherine T; Holmes, Avram J; Pizzagalli, Diego A

2008-09-01

Cognitive theories of depression posit that automatically activated cognitive schemas, including negative thoughts about the self and the future, predispose individuals to develop depressive disorders. However, prior research has largely examined these constructs using explicit tests in currently depressed individuals. Using the Implicit Association Test (IAT), the present study examined automatic associations between the self and mood state ("depression IAT") and between the future and mood state ("hopelessness IAT") before and after a negative mood induction in 19 remitted depressed individuals and 23 healthy controls. In the depression IAT, remitted depressed participants exhibited an overall lower tendency to associate themselves with happiness relative to the healthy controls before the mood induction. Control, but not remitted depressed, participants' automatic associations between the self and happiness diminished following the mood induction. Contrary to our hypotheses, no significant findings emerged when considering the hopelessness IAT. Consistent with prior studies, no significant correlations emerged between implicit and explicit biases, suggesting that these measures probe different processes. Results extend prior IAT research by documenting the presence of a reduced tendency to associate the self with happiness in a sample at increased risk for depression.

What Changes in Cognitive Therapy for Depression? An Examination of Cognitive Therapy Skills and Maladaptive Beliefs

PubMed Central

Adler, Abby D.; Strunk, Daniel R.; Fazio, Russell H.

2015-01-01

This study examined effortful cognitive skills and underlying maladaptive beliefs among patients treated with Cognitive Therapy for depression (CT). Depressed patients (n = 44) completed cognitive measures before and after 16 weeks of CT. Measures included: an assessment of CT skills (Ways of Responding Scale, WOR), an implicit test of maladaptive beliefs (Implicit Association Test, IAT), and a self-report questionnaire of maladaptive beliefs (Dysfunctional Attitude Scale, DAS). A matched sample of never-depressed participants (n = 44) also completed study measures. Prior to treatment, depressed patients endorsed significantly more undesirable cognitions on the WOR, IAT, and DAS compared to never-depressed participants. Patients displayed improvement on the WOR and DAS over the course of treatment, but showed no change on the IAT. Additionally, improvements on the WOR and DAS were each related to greater reductions in depressive symptoms. Results suggest that the degree of symptom reduction among patients participating in CT is related to changes in patients’ acquisition of coping skills requiring deliberate efforts and reflective thought, but not related to reduced endorsement of implicitly-assessed maladaptive beliefs. PMID:25526838

Stress-related biomarkers of dream recall and implicit memory under anaesthesia.

PubMed

Aceto, P; Lai, C; Perilli, V; Dello Russo, C; Federico, B; Navarra, P; Proietti, R; Sollazzi, L

2013-11-01

The aim of this study was to investigate whether auditory presentation of a story during general anaesthesia might influence stress hormone changes and thus affecting dream recall and/or implicit memory. One hundred and ten patients were randomly assigned either to hear a recording of a story through headphones or to have routine care with no auditory recording while undergoing laparoscopic cholecystectomy. Anaesthesia was standardised. Blood samples for cortisol and prolactin assays were collected 20 min before anaesthesia and 5 min after pneumoperitoneum. Dream recall and explicit/implicit memory were investigated upon awakening from anaesthesia and approximately 24 h after the end of the operation. Auditory presentation was associated with lower intra-operative serum prolactin concentration compared with control (p = 0.0006). Twenty-seven patients with recall of dreaming showed higher intra-operative prolactin (p = 0.004) and lower cortisol (p = 0.03) concentrations compared with those without dream recall. The knowledge of this interaction might be useful in the quest to ensure postoperative amnesia. © 2013 The Association of Anaesthetists of Great Britain and Ireland.

Personal attitudes toward time: The relationship between temporal focus, space-time mappings and real life experiences.

PubMed

Li, Heng; Cao, Yu

2017-06-01

What influences how people implicitly associate "past" and "future" with "front" and "back?" Whereas previous research has shown that cultural attitudes toward time play a role in modulating space-time mappings in people's mental models (de la Fuente, Santiago, Román, Dumitrache & Casasanto, 2014), we investigated real life experiences as potential additional influences on these implicit associations. Participants within the same single culture, who are engaged in different intermediate-term educational experiences (Study 1), long-term living experiences (Study 2), and short-term visiting experiences (Study 3), showed their distinct differences in temporal focus, thereby influencing their implicit spatializations of time. Results across samples suggest that personal attitudes toward time related to real life experiences may influence people's space-time mappings. The findings we report on shed further light on the high flexibility of human conceptualization system. While culture may exert an important influence on temporal focus, a person's conceptualization of time may be attributed to a culmination of factors. © 2017 Scandinavian Psychological Associations and John Wiley & Sons Ltd.

Investigations of Takeout proteins' ligand binding and release mechanism using molecular dynamics simulation.

PubMed

Zhang, Huijing; Yu, Hui; Zhao, Xi; Liu, Xiaoguang; Feng, Xianli; Huang, Xuri

2017-05-01

Takeout (To) proteins exist in a diverse range of insect species. They are involved in many important processes of insect physiology and behaviors. As the ligand carriers, To proteins can transport the small molecule to the target tissues. However, ligand release mechanism of To proteins is unclear so far. In this contribution, the process and pathway of the ligand binding and release are revealed by conventional molecular dynamics simulation, steered molecular dynamics simulation and umbrella sampling methods. Our results show that the α4-side of the protein is the unique gate for the ligand binding and release. The structural analysis confirms that the internal cavity of the protein has high rigidity, which is in accordance with the recent experimental results. By using the potential of mean force calculations in combination with residue cross correlation calculation, we concluded that the binding between the ligand and To proteins is a process of conformational selection. Furthermore, the conformational changes of To proteins and the hydrophobic interactions both are the key factors for ligand binding and release.

Organic Complexation of Dissolved Copper and Iron from Shipboard Incubations in the Central California Current System: Investigating the Impacts of Light Conditions and Phytoplankton Growth on Iron- and Copper-Binding Ligand Characteristics

NASA Astrophysics Data System (ADS)

Mellett, T.; Parker, C.; Brown, M.; Coale, T.; Duckham, C.; Chappell, D.; Maldonado, M. T.; Bruland, K. W.; Buck, K. N.

2016-02-01

Two shipboard incubation experiments were carried out in July of 2014 to investigate potential sources and sinks of iron- and copper-binding organic ligands in the surface ocean. Seawater for the experiments was collected from the central California Current System (cCCS) and incubated under varying light conditions and in the presence and absence of natural phytoplankton communities. Incubation treatments were sampled over a period of up to 3 days for measurements of total dissolved copper and iron, and for the concentration and conditional stability constants of copper- and iron-binding organic ligands. Dissolved copper and iron were determined by inductively coupled plasma-mass spectrometry (ICP-MS) following preconcentration on a Nobias PA1 resin. Organic ligand characteristics for iron and copper were determined using a method of competitive ligand exchange-absorptive cathodic stripping voltammetry (CLE-ACSV) with the added competing ligand salicylaldoxime. Trends in ligand concentrations and conditional stability constants across the different treatments and over the course of the incubation experiments will be presented.

Energetics of Glutamate Binding to an Ionotropic Glutamate Receptor.

PubMed

Yu, Alvin; Lau, Albert Y

2017-11-22

Ionotropic glutamate receptors (iGluRs) are ligand-gated ion channels that are responsible for the majority of excitatory transmission at the synaptic cleft. Mechanically speaking, agonist binding to the ligand binding domain (LBD) activates the receptor by triggering a conformational change that is transmitted to the transmembrane region, opening the ion channel pore. We use fully atomistic molecular dynamics simulations to investigate the binding process in the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor, an iGluR subtype. The string method with swarms of trajectories was applied to calculate the possible pathways glutamate traverses during ligand binding. Residues peripheral to the binding cleft are found to metastably bind the ligand prior to ligand entry into the binding pocket. Umbrella sampling simulations were performed to compute the free energy barriers along the binding pathways. The calculated free energy profiles demonstrate that metastable interactions contribute substantially to the energetics of ligand binding and form local minima in the overall free energy landscape. Protein-ligand interactions at sites outside of the orthosteric agonist-binding site may serve to lower the transition barriers of the binding process.

Gifted Students' Implicit Beliefs about Intelligence and Giftedness

ERIC Educational Resources Information Center

Makel, Matthew C.; Snyder, Kate E.; Thomas, Chandler; Malone, Patrick S.; Putallaz, Martha

2015-01-01

Growing attention is being paid to individuals' implicit beliefs about the nature of intelligence. However, implicit beliefs about giftedness are currently underexamined. In the current study, we examined academically gifted adolescents' implicit beliefs about both intelligence and giftedness. Overall, participants' implicit beliefs about…

Anatomy structure creation and editing using 3D implicit surfaces

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hibbard, Lyndon S.

2012-05-15

Purpose: To accurately reconstruct, and interactively reshape 3D anatomy structures' surfaces using small numbers of 2D contours drawn in the most visually informative views of 3D imagery. The innovation of this program is that the number of 2D contours can be very much smaller than the number of transverse sections, even for anatomy structures spanning many sections. This program can edit 3D structures from prior segmentations, including those from autosegmentation programs. The reconstruction and surface editing works with any image modality. Methods: Structures are represented by variational implicit surfaces defined by weighted sums of radial basis functions (RBFs). Such surfacesmore » are smooth, continuous, and closed and can be reconstructed with RBFs optimally located to efficiently capture shape in any combination of transverse (T), sagittal (S), and coronal (C) views. The accuracy of implicit surface reconstructions was measured by comparisons with the corresponding expert-contoured surfaces in 103 prostate cancer radiotherapy plans. Editing a pre-existing surface is done by overdrawing its profiles in image views spanning the affected part of the structure, deleting an appropriate set of prior RBFs, and merging the remainder with the new edit contour RBFs. Two methods were devised to identify RBFs to be deleted based only on the geometry of the initial surface and the locations of the new RBFs. Results: Expert-contoured surfaces were compared with implicit surfaces reconstructed from them over varying numbers and combinations of T/S/C planes. Studies revealed that surface-surface agreement increases monotonically with increasing RBF-sample density, and that the rate of increase declines over the same range. These trends were observed for all surface agreement metrics and for all the organs studied--prostate, bladder, and rectum. In addition, S and C contours may convey more shape information than T views for CT studies in which the axial slice thickness is greater than the pixel size. Surface editing accuracy likewise improves with larger sampling densities, and the rate of improvement similarly declines over the same conditions. Conclusions: Implicit surfaces based on RBFs are accurate representations of anatomic structures and can be interactively generated or modified to correct segmentation errors. The number of input contours is typically smaller than the number of T contours spanned by the structure.« less

On the Relationship Between Automatic Attitudes and Self-Reported Sexual Assault in Men

PubMed Central

Widman, Laura; Olson, Michael

2013-01-01

Research and theory suggest rape supportive attitudes are important predictors of sexual assault; yet, to date, rape supportive attitudes have been assessed exclusively through self-report measures that are methodologically and theoretically limited. To address these limitations, the objectives of the current project were to: (1) develop a novel implicit rape attitude assessment that captures automatic attitudes about rape and does not rely on self-reports, and (2) examine the association between automatic rape attitudes and sexual assault perpetration. We predicted that automatic rape attitudes would be a significant unique predictor of sexual assault even when self-reported rape attitudes (i.e., rape myth acceptance and hostility toward women) were controlled. We tested the generalizability of this prediction in two independent samples: a sample of undergraduate college men (n = 75, M age = 19.3 years) and a sample of men from the community (n = 50, M age = 35.9 years). We found the novel implicit rape attitude assessment was significantly associated with the frequency of sexual assault perpetration in both samples and contributed unique variance in explaining sexual assault beyond rape myth acceptance and hostility toward women. We discuss the ways in which future research on automatic rape attitudes may significantly advance measurement and theory aimed at understanding and preventing sexual assault. PMID:22618119

Implicit and explicit self-esteem in currently depressed individuals with and without suicidal ideation.

PubMed

Franck, Erik; De Raedt, Rudi; Dereu, Mieke; Van den Abbeele, Dirk

2007-03-01

In the present study, we have further explored implicit self-esteem in currently depressed individuals. Since suicidal ideation is associated with lower self-esteem in depressed individuals, we measured both implicit and explicit self-esteem in a population of currently depressed (CD) individuals, with and without suicidal ideation (SI), and in a group of non-depressed controls (ND). The results indicate that only CD individuals with SI show a discrepancy between their implicit and explicit self-esteem: that is, they exhibit high implicit and low explicit self-esteem. CD individuals without SI exhibit both low implicit and low explicit self-esteem; and ND controls exhibit both normal implicit and normal explicit self-esteem. These results provide new insights in the study of implicit self-esteem and the combination of implicit and explicit self-esteem in depression.

I like myself but I don't know why: enhancing implicit self-esteem by subliminal evaluative conditioning.

PubMed

Dijksterhuis, Ap

2004-02-01

On the basis of a conceptualization of implicit self-esteem as the implicit attitude toward the self, it was predicted that implicit self-esteem could be enhanced by subliminal evaluative conditioning. In 5 experiments, participants were repeatedly presented with trials in which the word I was paired with positive trait terms. Relative to control conditions, this procedure enhanced implicit self-esteem. The effects generalized across 3 measures of implicit self-esteem (Experiments 1-3). Furthermore, evaluative conditioning enhanced implicit self-esteem among people with low-temporal implicit self-esteem and among people with high-temporal implicit self-esteem (Experiment 4). In addition, it was shown that conditioning enhanced self-esteem to such an extent that it made participants insensitive to negative intelligence feedback (Experiments 5a and 5b). Various implications are discussed.

Phase transfer of 1- and 2-dimensional Cd-based nanocrystals

NASA Astrophysics Data System (ADS)

Kodanek, Torben; Banbela, Hadeel M.; Naskar, Suraj; Adel, Patrick; Bigall, Nadja C.; Dorfs, Dirk

2015-11-01

In this work, luminescent CdSe@CdS dot-in-rod nanocrystals, CdSe@CdS/ZnS nanorods as well as CdSe-CdS core-crown nanoplatelets were transferred into aqueous phase via ligand exchange reactions. For this purpose, bifunctional thiol-based ligands were employed, namely mercaptoacetic acid (MAA), 3-mercaptopropionic acid (MPA), 11-mercaptoundecanoic acid (MUA) as well as 2-(dimethylamino)ethanthiol (DMAET). Systematic investigations by means of photoluminescence quantum yield measurements as well as photoluminescence decay measurements have shown that the luminescence properties of the transferred nanostructures are affected by hole traps (induced by the thiol ligands themselves) as well as by spatial insulation and passivation against the environment. The influence of the tips of the nanorods on the luminescence is, however, insignificant. Accordingly, different ligands yield optimum results for different nanoparticle samples, mainly depending on the inorganic passivation of the respective samples. In case of CdSe@CdS nanorods, the highest emission intensities have been obtained by using short-chain ligands for the transfer preserving more than 50% of the pristine quantum yield of the hydrophobic nanorods. As opposed to this, the best possible quantum efficiency for the CdSe@CdS/ZnS nanorods has been achieved via MUA. The gained knowledge could be applied to transfer for the first time 2-dimensional CdSe-CdS core-crown nanoplatelets into water while preserving significant photoluminescence (up to 12% quantum efficiency).In this work, luminescent CdSe@CdS dot-in-rod nanocrystals, CdSe@CdS/ZnS nanorods as well as CdSe-CdS core-crown nanoplatelets were transferred into aqueous phase via ligand exchange reactions. For this purpose, bifunctional thiol-based ligands were employed, namely mercaptoacetic acid (MAA), 3-mercaptopropionic acid (MPA), 11-mercaptoundecanoic acid (MUA) as well as 2-(dimethylamino)ethanthiol (DMAET). Systematic investigations by means of photoluminescence quantum yield measurements as well as photoluminescence decay measurements have shown that the luminescence properties of the transferred nanostructures are affected by hole traps (induced by the thiol ligands themselves) as well as by spatial insulation and passivation against the environment. The influence of the tips of the nanorods on the luminescence is, however, insignificant. Accordingly, different ligands yield optimum results for different nanoparticle samples, mainly depending on the inorganic passivation of the respective samples. In case of CdSe@CdS nanorods, the highest emission intensities have been obtained by using short-chain ligands for the transfer preserving more than 50% of the pristine quantum yield of the hydrophobic nanorods. As opposed to this, the best possible quantum efficiency for the CdSe@CdS/ZnS nanorods has been achieved via MUA. The gained knowledge could be applied to transfer for the first time 2-dimensional CdSe-CdS core-crown nanoplatelets into water while preserving significant photoluminescence (up to 12% quantum efficiency). Electronic supplementary information (ESI) available: Further TEM images, further extinction spectra, particle size distribution and discussion about optical properties of the hydrophobic nanostructures. See DOI: 10.1039/c5nr06221g

Implicit cognitive aggression among young male prisoners: Association with dispositional and current aggression.

PubMed

Ireland, Jane L; Adams, Christine

2015-01-01

The current study explores associations between implicit and explicit aggression in young adult male prisoners, seeking to apply the Reflection-Impulsive Model and indicate parity with elements of the General Aggression Model and social cognition. Implicit cognitive aggressive processing is not an area that has been examined among prisoners. Two hundred and sixty two prisoners completed an implicit cognitive aggression measure (Puzzle Test) and explicit aggression measures, covering current behaviour (DIPC-R) and aggression disposition (AQ). It was predicted that dispositional aggression would be predicted by implicit cognitive aggression, and that implicit cognitive aggression would predict current engagement in aggressive behaviour. It was also predicted that more impulsive implicit cognitive processing would associate with aggressive behaviour whereas cognitively effortful implicit cognitive processing would not. Implicit aggressive cognitive processing was associated with increased dispositional aggression but not current reports of aggressive behaviour. Impulsive implicit cognitive processing of an aggressive nature predicted increased dispositional aggression whereas more cognitively effortful implicit cognitive aggression did not. The article concludes by outlining the importance of accounting for implicit cognitive processing among prisoners and the need to separate such processing into facets (i.e. impulsive vs. cognitively effortful). Implications for future research and practice in this novel area of study are indicated. Copyright © 2015 Elsevier Ltd. All rights reserved.

A Framework for Integrating Implicit Bias Recognition Into Health Professions Education.

PubMed

Sukhera, Javeed; Watling, Chris

2018-01-01

Existing literature on implicit bias is fragmented and comes from a variety of fields like cognitive psychology, business ethics, and higher education, but implicit-bias-informed educational approaches have been underexplored in health professions education and are difficult to evaluate using existing tools. Despite increasing attention to implicit bias recognition and management in health professions education, many programs struggle to meaningfully integrate these topics into curricula. The authors propose a six-point actionable framework for integrating implicit bias recognition and management into health professions education that draws on the work of previous researchers and includes practical tools to guide curriculum developers. The six key features of this framework are creating a safe and nonthreatening learning context, increasing knowledge about the science of implicit bias, emphasizing how implicit bias influences behaviors and patient outcomes, increasing self-awareness of existing implicit biases, improving conscious efforts to overcome implicit bias, and enhancing awareness of how implicit bias influences others. Important considerations for designing implicit-bias-informed curricula-such as individual and contextual variables, as well as formal and informal cultural influences-are discussed. The authors also outline assessment and evaluation approaches that consider outcomes at individual, organizational, community, and societal levels. The proposed framework may facilitate future research and exploration regarding the use of implicit bias in health professions education.

Factors affecting articulation skills in children with velocardiofacial syndrome and children with cleft palate or velopharyngeal dysfunction: A preliminary report

PubMed Central

Baylis, Adriane L.; Munson, Benjamin; Moller, Karlind T.

2010-01-01

Objective To examine the influence of speech perception, cognition, and implicit phonological learning on articulation skills of children with Velocardiofacial syndrome (VCFS) and children with cleft palate or velopharyngeal dysfunction (VPD). Design Cross-sectional group experimental design. Participants 8 children with VCFS and 5 children with non-syndromic cleft palate or VPD. Methods and Measures All children participated in a phonetic inventory task, speech perception task, implicit priming nonword repetition task, conversational sample, nonverbal intelligence test, and hearing screening. Speech tasks were scored for percentage of phonemes correctly produced. Group differences and relations among measures were examined using nonparametric statistics. Results Children in the VCFS group demonstrated significantly poorer articulation skills and lower standard scores of nonverbal intelligence compared to the children with cleft palate or VPD. There were no significant group differences in speech perception skills. For the implicit priming task, both groups of children were more accurate in producing primed nonwords than unprimed nonwords. Nonverbal intelligence and severity of velopharyngeal inadequacy for speech were correlated with articulation skills. Conclusions In this study, children with VCFS had poorer articulation skills compared to children with cleft palate or VPD. Articulation difficulties seen in the children with VCFS did not appear to be associated with speech perception skills or the ability to learn new phonological representations. Future research should continue to examine relationships between articulation, cognition, and velopharyngeal dysfunction in a larger sample of children with cleft palate and VCFS. PMID:18333642

Screening of the binding of small molecules to proteins by desorption electrospray ionization mass spectrometry combined with protein microarray.

PubMed

Yao, Chenxi; Wang, Tao; Zhang, Buqing; He, Dacheng; Na, Na; Ouyang, Jin

2015-11-01

The interaction between bioactive small molecule ligands and proteins is one of the important research areas in proteomics. Herein, a simple and rapid method is established to screen small ligands that bind to proteins. We designed an agarose slide to immobilize different proteins. The protein microarrays were allowed to interact with different small ligands, and after washing, the microarrays were screened by desorption electrospray ionization mass spectrometry (DESI MS). This method can be applied to screen specific protein binding ligands and was shown for seven proteins and 34 known ligands for these proteins. In addition, a high-throughput screening was achieved, with the analysis requiring approximately 4 s for one sample spot. We then applied this method to determine the binding between the important protein matrix metalloproteinase-9 (MMP-9) and 88 small compounds. The molecular docking results confirmed the MS results, demonstrating that this method is suitable for the rapid and accurate screening of ligands binding to proteins. Graphical Abstract ᅟ.

Ligand Fishing: A Remarkable Strategy for Discovering Bioactive Compounds from Complex Mixture of Natural Products.

PubMed

Zhuo, Rongjie; Liu, Hao; Liu, Ningning; Wang, Yi

2016-11-11

Identification of active compounds from natural products is a critical and challenging task in drug discovery pipelines. Besides commonly used bio-guided screening approaches, affinity selection strategy coupled with liquid chromatography or mass spectrometry, known as ligand fishing, has been gaining increasing interest from researchers. In this review, we summarized this emerging strategy and categorized those methods as off-line or on-line mode according to their features. The separation principles of ligand fishing were introduced based on distinct analytical techniques, including biochromatography, capillary electrophoresis, ultrafiltration, equilibrium dialysis, microdialysis, and magnetic beads. The applications of ligand fishing approaches in the discovery of lead compounds were reviewed. Most of ligand fishing methods display specificity, high efficiency, and require less sample pretreatment, which makes them especially suitable for screening active compounds from complex mixtures of natural products. We also summarized the applications of ligand fishing in the modernization of Traditional Chinese Medicine (TCM), and propose some perspectives of this remarkable technique.

A decade of studying implicit racial/ethnic bias in healthcare providers using the implicit association test.

PubMed

Maina, Ivy W; Belton, Tanisha D; Ginzberg, Sara; Singh, Ajit; Johnson, Tiffani J

2018-02-01

Disparities in the care and outcomes of US racial/ethnic minorities are well documented. Research suggests that provider bias plays a role in these disparities. The implicit association test enables measurement of implicit bias via tests of automatic associations between concepts. Hundreds of studies have examined implicit bias in various settings, but relatively few have been conducted in healthcare. The aim of this systematic review is to synthesize the current knowledge on the role of implicit bias in healthcare disparities. A comprehensive literature search of several databases between May 2015 and September 2016 identified 37 qualifying studies. Of these, 31 found evidence of pro-White or light-skin/anti-Black, Hispanic, American Indian or dark-skin bias among a variety of HCPs across multiple levels of training and disciplines. Fourteen studies examined the association between implicit bias and healthcare outcomes using clinical vignettes or simulated patients. Eight found no statistically significant association between implicit bias and patient care while six studies found that higher implicit bias was associated with disparities in treatment recommendations, expectations of therapeutic bonds, pain management, and empathy. All seven studies that examined the impact of implicit provider bias on real-world patient-provider interaction found that providers with stronger implicit bias demonstrated poorer patient-provider communication. Two studies examined the effect of implicit bias on real-world clinical outcomes. One found an association and the other did not. Two studies tested interventions aimed at reducing bias, but only one found a post-intervention reduction in implicit bias. This review reveals a need for more research exploring implicit bias in real-world patient care, potential modifiers and confounders of the effect of implicit bias on care, and strategies aimed at reducing implicit bias and improving patient-provider communication. Future studies have the opportunity to build on this current body of research, and in doing so will enable us to achieve equity in healthcare and outcomes. Copyright © 2017 Elsevier Ltd. All rights reserved.

Concentration, Complexation and Chemical Speciation of Zinc and Cadmium in the Western North Pacific Ocean : Exploring Sources and Transport of Trace Metals and Complexing Ligands.

NASA Astrophysics Data System (ADS)

Carrasco, G. G.; Morton, P. L.; Donat, J. R.

2008-12-01

We determined Zn and Cd total dissolved (0.45 µm-filtered) concentrations, organic complexation and chemical speciation in surface water samples collected along the transect of the 2002 IOC Baseline Contaminant Survey expedition in the Western North Pacific and in vertical profile water samples at nine stations. The goals of this work were (1) to compare and contrast various trace metal sources, including both natural and anthropogenic atmospheric deposition, upwelling, marginal seas and others; (2) to study the organic ligand sources, generally thought to be phytoplankton; and (3) to investigate metal and ligand transport mechanisms, residence times and eventual upwelling in the Eastern North Pacific. Total dissolved (TD) Zn and Cd values were obtained using a combination of differential pulse stripping anodic voltammetry (DPASV), preconcentration with 8-HQ or APDC/DDC and quantification at ICPMS or AA. Organic complexation and chemical speciation of Zn and Cd were determined simultaneously using DPASV at a thin-mercury-film, glassy-carbon-disk-electrode. Surface transect TDZn and TDCd concentrations were low in the Subtropical Gyre (STG), in contrast with high values in the Western Subarctic Gyre (WSG). Zn and Cd were organically complexed in most surface samples: at least one ligand class was detected for Zn and Cd, whose conditional stability constants (log K') averaged 10.2 and 10.5, respectively. These ligands were found in excess of the total dissolved metal throughout the region of study except in the WSG for Cd. Vertical distributions of TDZn and TDCd exhibited nutrient-type profiles for all the STG stations. While constant Zn/Si and Cd/P values were observed throughout the water column in the WSG, some deviations were observed within the STG. In addition, the mode and intermediate water masses of the STG displayed very high concentrations of a Zn-complexing ligand (log K' 10.0) in excess of TDZn. As these water masses moved eastward, we observed that the ligand concentrations decreased. In contrast to the STG, the upper 1000m of the WSG showed elevated concentrations of both metals. Despite elevated surface (0-200m) Zn concentrations (~2nM), a Zn-complexing ligand (log K' 9.8) was found in excess of TDZn; below the photic layer, even higher TDZn concentrations might have saturated the ligand. A ligand for Cd was present in lower-than-TDCd concentrations in the same surface waters; below them, organic complexation of Cd was observed rarely in both STG and WSG regions. By studying the geographic distribution of the total dissolved metals and ligands, along with other dissolved and particulate tracers, possible sources and transport mechanisms can be contrasted and evaluated. Furthermore, the influence of these sources and transport mechanisms on the distribution of Zn and Cd chemical species and, ultimately, the bioavailability of these micronutrient metals can be studied.

Nature and Nurture Strike (Out) Again.

ERIC Educational Resources Information Center

Scarr, Sandra; Weinberg, Richard A.

1979-01-01

A reply to Plomin's critique and some criticisms of Munsinger's review of adopted child literature are presented. Selective bias in adoptee samples, implicit assumptions in models that lead to heritability estimates, and problems produced by lack of an accepted model of environmental transmission are also discussed. (Author/RD)

Unconscious Motivation. Part I: Implicit Attitudes toward L2 Speakers

ERIC Educational Resources Information Center

Al-Hoorie, Ali H.

2016-01-01

This paper reports the first investigation in the second language acquisition field assessing learners' implicit attitudes using the Implicit Association Test, a computerized reaction-time measure. Examination of the explicit and implicit attitudes of Arab learners of English (N = 365) showed that, particularly for males, implicit attitudes toward…

Efficient Bayesian parameter estimation with implicit sampling and surrogate modeling for a vadose zone hydrological problem

NASA Astrophysics Data System (ADS)

Liu, Y.; Pau, G. S. H.; Finsterle, S.

2015-12-01

Parameter inversion involves inferring the model parameter values based on sparse observations of some observables. To infer the posterior probability distributions of the parameters, Markov chain Monte Carlo (MCMC) methods are typically used. However, the large number of forward simulations needed and limited computational resources limit the complexity of the hydrological model we can use in these methods. In view of this, we studied the implicit sampling (IS) method, an efficient importance sampling technique that generates samples in the high-probability region of the posterior distribution and thus reduces the number of forward simulations that we need to run. For a pilot-point inversion of a heterogeneous permeability field based on a synthetic ponded infiltration experiment simu­lated with TOUGH2 (a subsurface modeling code), we showed that IS with linear map provides an accurate Bayesian description of the parameterized permeability field at the pilot points with just approximately 500 forward simulations. We further studied the use of surrogate models to improve the computational efficiency of parameter inversion. We implemented two reduced-order models (ROMs) for the TOUGH2 forward model. One is based on polynomial chaos expansion (PCE), of which the coefficients are obtained using the sparse Bayesian learning technique to mitigate the "curse of dimensionality" of the PCE terms. The other model is Gaussian process regression (GPR) for which different covariance, likelihood and inference models are considered. Preliminary results indicate that ROMs constructed based on the prior parameter space perform poorly. It is thus impractical to replace this hydrological model by a ROM directly in a MCMC method. However, the IS method can work with a ROM constructed for parameters in the close vicinity of the maximum a posteriori probability (MAP) estimate. We will discuss the accuracy and computational efficiency of using ROMs in the implicit sampling procedure for the hydrological problem considered. This work was supported, in part, by the U.S. Dept. of Energy under Contract No. DE-AC02-05CH11231

Implicit self-esteem decreases in adolescence: a cross-sectional study.

PubMed

Cai, Huajian; Wu, Mingzheng; Luo, Yu L L; Yang, Jing

2014-01-01

Implicit self-esteem has remained an active research topic in both the areas of implicit social cognition and self-esteem in recent decades. The purpose of this study is to explore the development of implicit self-esteem in adolescents. A total of 599 adolescents from junior and senior high schools in East China participated in the study. They ranged in age from 11 to 18 years with a mean age of 14.10 (SD = 2.16). The degree of implicit self-esteem was assessed using the Implicit Association Test (IAT) with the improved D score as the index. Participants also completed the Rosenberg Self-Esteem Scale (α = 0.77). For all surveyed ages, implicit self-esteem was positively biased, all ts>8.59, all ps<0.001. The simple correlation between implicit self-esteem and age was significant, r =  -.25, p = 1. 10(-10). A regression with implicit self-esteem as the criterion variable, and age, gender, and age × gender interaction as predictors further revealed the significant negative linear relationship between age and implicit self-esteem, β = -0.19, t = -3.20, p = 0.001. However, explicit self-esteem manifested a reverse "U" shape throughout adolescence. Implicit self-esteem in adolescence manifests a declining trend with increasing age, suggesting that it is sensitive to developmental or age-related changes. This finding enriches our understanding of the development of implicit social cognition.

Using Implicit Measures to Highlight Science Teachers' Implicit Theories of Intelligence

ERIC Educational Resources Information Center

Mascret, Nicolas; Roussel, Peggy; Cury, François

2015-01-01

Using an innovative method, a Single-Target Implicit Association Test (ST-IAT) was created to explore the implicit theories of intelligence among science and liberal arts teachers and their relationships with their gender. The results showed that for science teachers--especially for male teachers--there was a negative implicit association between…

The Roles of Implicit Understanding of Engineering Ethics in Student Teams' Discussion.

PubMed

Lee, Eun Ah; Grohman, Magdalena; Gans, Nicholas R; Tacca, Marco; Brown, Matthew J

2017-12-01

Following previous work that shows engineering students possess different levels of understanding of ethics-implicit and explicit-this study focuses on how students' implicit understanding of engineering ethics influences their team discussion process, in cases where there is significant divergence between their explicit and implicit understanding. We observed student teams during group discussions of the ethical issues involved in their engineering design projects. Through the micro-scale discourse analysis based on cognitive ethnography, we found two possible ways in which implicit understanding influenced the discussion. In one case, implicit understanding played the role of intuitive ethics-an intuitive judgment followed by reasoning. In the other case, implicit understanding played the role of ethical insight, emotionally guiding the direction of the discussion. In either case, however, implicit understanding did not have a strong influence, and the conclusion of the discussion reflected students' explicit understanding. Because students' implicit understanding represented broader social implication of engineering design in both cases, we suggest to take account of students' relevant implicit understanding in engineering education, to help students become more socially responsible engineers.

TINS, target immobilized NMR screening: an efficient and sensitive method for ligand discovery.

PubMed

Vanwetswinkel, Sophie; Heetebrij, Robert J; van Duynhoven, John; Hollander, Johan G; Filippov, Dmitri V; Hajduk, Philip J; Siegal, Gregg

2005-02-01

We propose a ligand screening method, called TINS (target immobilized NMR screening), which reduces the amount of target required for the fragment-based approach to drug discovery. Binding is detected by comparing 1D NMR spectra of compound mixtures in the presence of a target immobilized on a solid support to a control sample. The method has been validated by the detection of a variety of ligands for protein and nucleic acid targets (K(D) from 60 to 5000 muM). The ligand binding capacity of a protein was undiminished after 2000 different compounds had been applied, indicating the potential to apply the assay for screening typical fragment libraries. TINS can be used in competition mode, allowing rapid characterization of the ligand binding site. TINS may allow screening of targets that are difficult to produce or that are insoluble, such as membrane proteins.

Influence of surface states of CuInS2 quantum dots in quantum dots sensitized photo-electrodes

NASA Astrophysics Data System (ADS)

Peng, Zhuoyin; Liu, Yueli; Wu, Lei; Zhao, Yinghan; Chen, Keqiang; Chen, Wen

2016-12-01

Surface states are significant factor for the enhancement of electrochemical performance in CuInS2 quantum dot sensitized photo-electrodes. DDT, OLA, MPA, and S2- ligand capped CuInS2 quantum dot sensitized photo-electrodes are prepared by thermolysis, solvethermal and ligand-exchange processes, respectively, and their optical properties and photoelectrochemical properties are investigated. The S2- ligand enhances the UV-vis absorption and electron-hole separation property as well as the excellent charge transfer performance of the photo-electrodes, which is attributed to the fact that the atomic S2- ligand for the interfacial region of quantum dots may improve the electron transfer rate. These S2--capped CuInS2 quantum dot sensitized photo-electrodes exhibit the excellent photoelectrochemical efficiency and IPCE peak value, which is higher than that of the samples with DDT, OLA and MPA ligands.

Synthesis and characterization of ligational behavior of curcumin drug towards some transition metal ions: Chelation effect on their thermal stability and biological activity

NASA Astrophysics Data System (ADS)

Refat, Moamen S.

2013-03-01

Complexes of Cr(III), Mn(II), Fe(III), Co(II), Ni(II), Cu(II) and Zn(II) with curcumin ligand as antitumor activity were synthesized and characterized by elemental analysis, conductometry, magnetic susceptibility, UV-Vis, IR, Raman, ESR, 1H-NMR spectroscopy, X-ray diffraction analysis of powdered samples and thermal analysis, and screened for antimicrobial activity. The IR spectral data suggested that the ligand behaves as a monobasic bidentate ligand towards the central metal ion with an oxygen's donor atoms sequence of both sbnd OH and Cdbnd O groups under keto-enol structure. From the microanalytical data, the stoichiometry of the complexes 1:2 (metal:ligand) was found. The ligand and their metal complexes were screened for antibacterial activity against Escherichia Coli, Staphylococcus aureus, Bacillus subtilis and Pseudomonas aeruginosa and fungicidal activity against Aspergillus flavus and Candida albicans.

Assessment of implicit health attitudes: a multitrait-multimethod approach and a comparison between patients with hypochondriasis and patients with anxiety disorders.

PubMed

Weck, Florian; Höfling, Volkmar

2015-01-01

Two adaptations of the Implicit Association Task were used to assess implicit anxiety (IAT-Anxiety) and implicit health attitudes (IAT-Hypochondriasis) in patients with hypochondriasis (n = 58) and anxiety patients (n = 71). Explicit anxieties and health attitudes were assessed using questionnaires. The analysis of several multitrait-multimethod models indicated that the low correlation between explicit and implicit measures of health attitudes is due to the substantial methodological differences between the IAT and the self-report questionnaire. Patients with hypochondriasis displayed significantly more dysfunctional explicit and implicit health attitudes than anxiety patients, but no differences were found regarding explicit and implicit anxieties. The study demonstrates the specificity of explicit and implicit dysfunctional health attitudes among patients with hypochondriasis.

Can implicit appraisal concepts produce emotion-specific effects? A focus on unfairness and anger.

PubMed

Tong, Eddie M W; Tan, Deborah H; Tan, Yan Lin

2013-06-01

This research examined whether the non-conscious activation of an implicit appraisal concept could affect responses associated with the corresponding emotion as predicted by appraisal theories. Explicit and implicit emotional responses were examined. We focused on implicit unfairness and its effect on anger. The results show that subliminal activation of implicit unfairness affected implicit anger responses (anger facial expression and latency responses to anger words) but not explicit anger feelings (i.e., reported anger). The non-conscious effect of implicit unfairness was specific to anger, as no effect on sadness, fear, and guilt was found. Copyright © 2013 Elsevier Inc. All rights reserved.

The Intergenerational Transmission of Implicit and Explicit Attitudes Toward Smoking

PubMed Central

Sherman, Steven J.; Chassin, Laurie; Presson, Clark; Seo, Dong-Chul; Macy, Jonathan T.

2009-01-01

This study examined the intergenerational transmission of implicit and explicit attitudes toward smoking, as well as the role of these attitudes in adolescents’ smoking initiation. There was evidence of intergenerational transmission of implicit attitudes. Mothers who had more positive implicit attitudes had children with more positive implicit attitudes. In turn, these positive implicit attitudes of adolescents predicted their smoking initiation 18-months later. Moreover, these effects were obtained above and beyond the effects of explicit attitudes. These findings provide the first evidence that the intergenerational transmission of implicit cognition may play a role in the intergenerational transmission of an addictive behavior. PMID:20126293

On the nature of implicit soul beliefs: when the past weighs more than the present.

PubMed

Anglin, Stephanie M

2015-06-01

Intuitive childhood beliefs in dualism may lay the foundation for implicit soul and afterlife beliefs, which may diverge from explicit beliefs formed later in adulthood. Brief Implicit Association Tests were developed to investigate the relation of implicit soul and afterlife beliefs to childhood and current beliefs. Early but not current beliefs covaried with implicit beliefs. Results demonstrated greater discrepancies in current than in childhood soul and afterlife beliefs among religious groups, and no differences in implicit beliefs. These findings suggest that implicit soul and afterlife beliefs diverge from current self-reported beliefs, stemming instead from childhood beliefs. © 2014 The British Psychological Society.

Capturing doping attitudes by self-report declarations and implicit assessment: A methodology study

PubMed Central

Petróczi, Andrea; Aidman, Eugene V; Nepusz, Tamás

2008-01-01

Background Understanding athletes' attitudes and behavioural intentions towards performance enhancement is critical to informing anti-doping intervention strategies. Capturing the complexity of these attitudes beyond verbal declarations requires indirect methods. This pilot study was aimed at developing and validating a method to assess implicit doping attitudes using an Implicit Associations Test (IAT) approach. Methods The conventional IAT evaluation task (categorising 'good' and 'bad' words) was combined with a novel 'doping' versus 'nutrition supplements' category pair to create a performance-enhancement related IAT protocol (PE-IAT). The difference between average response times to 'good-doping' and 'bad-doping' combinations represents an estimate of implicit attitude towards doping in relation to nutritional supplements. 111 sports and exercise science undergraduates completed the PE-IAT, the Performance Enhancement Attitude Scale (PEAS) and answered questions regarding their beliefs about doping. Results Longer response times were observed in the mixed category discrimination trials where categories 'good' and 'doping' shared the same response key (compared to 'bad-doping' combination on the same key) indicating a less favourable evaluation of doping substances. The PE-IAT measure did not correlate significantly with the declared doping attitudes (r = .181, p = .142), indicating a predictable partial dissociation. Action-oriented self-report expressed stronger associations with PE-IAT: participants who declared they would consider using doping showed significantly less implicit negativity towards banned substances (U = 109.00, p = .047). Similarly, those who reported more lenient explicit attitudes towards doping or expressly supported legalizing it, showed less implicit negativity towards doping in the sample, although neither observed differences reached statistical significance (t = 1.300, p = .198, and U = 231.00, p = .319, respectively). Known-group validation strategy yielded mixed results: while competitive sport participants scored significantly lower than non-competitive ones on the PEAS (t = -2.71, p = .008), the two groups did not differ on PE-IAT (t = -.093, p = .926). Conclusion The results suggest a potential of the PE-IAT method to capture undeclared attitudes to doping and predict behaviour, which can support targeted anti-doping intervention and related research. The initial evidence of validity is promising but also indicates a need for improvement to the protocol and stimulus material. PMID:18426575

Islamophobia Pre- and Post-September 11th, 2001

ERIC Educational Resources Information Center

Sheridan, Lorraine P.

2006-01-01

Although much academic research has addressed racism, religious discrimination has been largely ignored. The current study investigates levels of self reported racial and religious discrimination in a sample of 222 British Muslims. Respondents indicate that following September 11th, 2001, levels of implicit or indirect discrimination rose by 82.6%…

Superior serum half life of albumin tagged TNF ligands

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mueller, Nicole; Schneider, Britta; Pfizenmaier, Klaus

2010-06-11

Due to their immune stimulating and apoptosis inducing properties, ligands of the TNF family attract increasing interest as therapeutic proteins. A general limitation of in vivo applications of recombinant soluble TNF ligands is their notoriously rapid clearance from circulation. To improve the serum half life of the TNF family members TNF, TWEAK and TRAIL, we genetically fused soluble variants of these molecules to human serum albumin (HSA). The serum albumin-TNF ligand fusion proteins were found to be of similar bioactivity as the corresponding HSA-less counterparts. Upon intravenous injection (i.v.), serum half life of HSA-TNF ligand fusion proteins, as determined bymore » ELISA, was around 15 h as compared to approximately 1 h for all of the recombinant control TNF ligands without HSA domain. Moreover, serum samples collected 6 or 24 h after i.v. injection still contained high TNF ligand bioactivity, demonstrating that there is only limited degradation/inactivation of circulating HSA-TNF ligand fusion proteins in vivo. In a xenotransplantation model, significantly less of the HSA-TRAIL fusion protein compared to the respective control TRAIL protein was required to achieve inhibition of tumor growth indicating that the increased half life of HSA-TNF ligand fusion proteins translates into better therapeutic action in vivo. In conclusion, our data suggest that genetic fusion to serum albumin is a powerful and generally applicable mean to improve bioavailability and in vivo activity of TNF ligands.« less

Multiple ligand simultaneous docking: orchestrated dancing of ligands in binding sites of protein.

PubMed

Li, Huameng; Li, Chenglong

2010-07-30

Present docking methodologies simulate only one single ligand at a time during docking process. In reality, the molecular recognition process always involves multiple molecular species. Typical protein-ligand interactions are, for example, substrate and cofactor in catalytic cycle; metal ion coordination together with ligand(s); and ligand binding with water molecules. To simulate the real molecular binding processes, we propose a novel multiple ligand simultaneous docking (MLSD) strategy, which can deal with all the above processes, vastly improving docking sampling and binding free energy scoring. The work also compares two search strategies: Lamarckian genetic algorithm and particle swarm optimization, which have respective advantages depending on the specific systems. The methodology proves robust through systematic testing against several diverse model systems: E. coli purine nucleoside phosphorylase (PNP) complex with two substrates, SHP2NSH2 complex with two peptides and Bcl-xL complex with ABT-737 fragments. In all cases, the final correct docking poses and relative binding free energies were obtained. In PNP case, the simulations also capture the binding intermediates and reveal the binding dynamics during the recognition processes, which are consistent with the proposed enzymatic mechanism. In the other two cases, conventional single-ligand docking fails due to energetic and dynamic coupling among ligands, whereas MLSD results in the correct binding modes. These three cases also represent potential applications in the areas of exploring enzymatic mechanism, interpreting noisy X-ray crystallographic maps, and aiding fragment-based drug design, respectively. 2010 Wiley Periodicals, Inc.

Changes of Explicit and Implicit Stigma in Medical Students during Psychiatric Clerkship.

PubMed

Wang, Peng-Wei; Ko, Chih-Hung; Chen, Cheng-Sheng; Yang, Yi-Hsin Connine; Lin, Huang-Chi; Cheng, Cheng-Chung; Tsang, Hin-Yeung; Wu, Ching-Kuan; Yen, Cheng-Fang

2016-04-01

This study examines the differences in explicit and implicit stigma between medical and non-medical undergraduate students at baseline; the changes of explicit and implicit stigma in medical undergraduate and non-medical undergraduate students after a 1-month psychiatric clerkship and 1-month follow-up period; and the differences in the changes of explicit and implicit stigma between medical and non-medical undergraduate students. Seventy-two medical undergraduate students and 64 non-medical undergraduate students were enrolled. All participants were interviewed at intake and after 1 month. The Taiwanese version of the Stigma Assessment Scale and the Implicit Association Test were used to measure the participants' explicit and implicit stigma. Neither explicit nor implicit stigma differed between two groups at baseline. The medical, but not the non-medical, undergraduate students had a significant decrease in explicit stigma during the 1-month period of follow-up. Neither the medical nor the non-medical undergraduate students exhibited a significant change in implicit stigma during the one-month of follow-up, however. There was an interactive effect between group and time on explicit stigma but not on implicit stigma. Explicit but not implicit stigma toward mental illness decreased in the medical undergraduate students after a psychiatric clerkship. Further study is needed to examine how to improve implicit stigma toward mental illness.

Not the Same Old Thing: Establishing the Unique Contribution of Drinking Identity as a Predictor of Alcohol Consumption and Problems Over Time

PubMed Central

Lindgren, Kristen P.; Ramirez, Jason J.; Olin, Cecilia C.; Neighbors, Clayton

2016-01-01

Drinking identity – how much individuals view themselves as drinkers– is a promising cognitive factor that predicts problem drinking. Implicit and explicit measures of drinking identity have been developed (the former assesses more reflexive/automatic cognitive processes; the latter more reflective/controlled cognitive processes): each predicts unique variance in alcohol consumption and problems. However, implicit and explicit identity’s utility and uniqueness as a predictor relative to cognitive factors important for problem drinking screening and intervention has not been evaluated. Thus, the current study evaluated implicit and explicit drinking identity as predictors of consumption and problems over time. Baseline measures of drinking identity, social norms, alcohol expectancies, and drinking motives were evaluated as predictors of consumption and problems (evaluated every three months over two academic years) in a sample of 506 students (57% female) in their first or second year of college. Results found that baseline identity measures predicted unique variance in consumption and problems over time. Further, when compared to each set of cognitive factors, the identity measures predicted unique variance in consumption and problems over time. Findings were more robust for explicit, versus, implicit identity and in models that did not control for baseline drinking. Drinking identity appears to be a unique predictor of problem drinking relative to social norms, alcohol expectancies, and drinking motives. Intervention and theory could benefit from including and considering drinking identity. PMID:27428756

Not the same old thing: Establishing the unique contribution of drinking identity as a predictor of alcohol consumption and problems over time.

PubMed

Lindgren, Kristen P; Ramirez, Jason J; Olin, Cecilia C; Neighbors, Clayton

2016-09-01

Drinking identity-how much individuals view themselves as drinkers-is a promising cognitive factor that predicts problem drinking. Implicit and explicit measures of drinking identity have been developed (the former assesses more reflexive/automatic cognitive processes; the latter more reflective/controlled cognitive processes): each predicts unique variance in alcohol consumption and problems. However, implicit and explicit identity's utility and uniqueness as predictors relative to cognitive factors important for problem drinking screening and intervention has not been evaluated. Thus, the current study evaluated implicit and explicit drinking identity as predictors of consumption and problems over time. Baseline measures of drinking identity, social norms, alcohol expectancies, and drinking motives were evaluated as predictors of consumption and problems (evaluated every 3 months over 2 academic years) in a sample of 506 students (57% female) in their first or second year of college. Results found that baseline identity measures predicted unique variance in consumption and problems over time. Further, when compared to each set of cognitive factors, the identity measures predicted unique variance in consumption and problems over time. Findings were more robust for explicit versus implicit identity and in models that did not control for baseline drinking. Drinking identity appears to be a unique predictor of problem drinking relative to social norms, alcohol expectancies, and drinking motives. Intervention and theory could benefit from including and considering drinking identity. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Solvent induced conformational fluctuation of alanine dipeptide studied by using vibrational probes

NASA Astrophysics Data System (ADS)

Cai, Kaicong; Du, Fenfen; Liu, Jia; Su, Tingting

2015-02-01

The solvation effect on the three dimensional structure and the vibrational feature of alanine dipeptide (ALAD) was evaluated by applying the implicit solvents from polarizable continuum solvent model (PCM) through ab initio calculations, by using molecular dynamic (MD) simulations with explicit solvents, and by combining these two approaches. The implicit solvent induced potential energy fluctuations of ALAD in CHCl3, DMSO and H2O are revealed by means of ab initio calculations, and a global view of conformational and solvation environmental dependence of amide I frequencies is achieved. The results from MD simulations with explicit solvents show that ALAD trends to form PPII, αL, αR, and C5 in water, PPII and C5 in DMSO, and C5 in CHCl3, ordered by population, and the demonstration of the solvated structure, the solute-solvent interaction and hydrogen bonding is therefore enhanced. Representative ALAD-solvent clusters were sampled from MD trajectories and undergone ab initio calculations. The explicit solvents reveal the hydrogen bonding between ALAD and solvents, and the correlation between amide I frequencies and the Cdbnd O bond length is built. The implicit solvents applied to the ALAD-solvent clusters further compensate the solvation effect from the bulk, and thus enlarge the degree of structural distortion and the amide I frequency red shift. The combination of explicit solvent in the first hydration shell and implicit solvent in the bulk is helpful for our understanding about the conformational fluctuation of solvated polypeptides through vibrational probes.

Intact implicit learning in autism spectrum conditions.

PubMed

Brown, Jamie; Aczel, Balazs; Jiménez, Luis; Kaufman, Scott Barry; Grant, Kate Plaisted

2010-09-01

Individuals with autism spectrum condition (ASC) have diagnostic impairments in skills that are associated with an implicit acquisition; however, it is not clear whether ASC individuals show specific implicit learning deficits. We compared ASC and typically developing (TD) individuals matched for IQ on five learning tasks: four implicit learning tasks--contextual cueing, serial reaction time, artificial grammar learning, and probabilistic classification learning tasks--that used procedures expressly designed to minimize the use of explicit strategies, and one comparison explicit learning task, paired associates learning. We found implicit learning to be intact in ASC. Beyond no evidence of differences, there was evidence of statistical equivalence between the groups on all the implicit learning tasks. This was not a consequence of compensation by explicit learning ability or IQ. Furthermore, there was no evidence to relate implicit learning to ASC symptomatology. We conclude that implicit mechanisms are preserved in ASC and propose that it is disruption by other atypical processes that impact negatively on the development of skills associated with an implicit acquisition.

The Relationship of Explicit-Implicit Evaluative Discrepancy to Exercise Dropout in Middle-Aged Adults.

PubMed

Berry, Tanya R; Rodgers, Wendy M; Divine, Alison; Hall, Craig

2018-06-19

Discrepancies between automatically activated associations (i.e., implicit evaluations) and explicit evaluations of motives (measured with a questionnaire) could lead to greater information processing to resolve discrepancies or self-regulatory failures that may affect behavior. This research examined the relationship of health and appearance exercise-related explicit-implicit evaluative discrepancies, the interaction between implicit and explicit evaluations, and the combined value of explicit and implicit evaluations (i.e., the summed scores) to dropout from a yearlong exercise program. Participants (N = 253) completed implicit health and appearance measures and explicit health and appearance motives at baseline, prior to starting the exercise program. The sum of implicit and explicit appearance measures was positively related to weeks in the program, and discrepancy between the implicit and explicit health measures was negatively related to length of time in the program. Implicit exercise evaluations and their relationships to oft-cited motives such as appearance and health may inform exercise dropout.

Structural studies of the molybdenum center of mitochondrial amidoxime reducing component (mARC) by pulsed EPR spectroscopy and 17O-labeling

PubMed Central

Rajapakshe, Asha; Astashkin, Andrei V.; Klein, Eric L.; Reichmann, Debora; Mendel, Ralf R.; Bittner, Florian; Enemark, John H.

2011-01-01

Mitochondrial amidoxime reducing components (mARC-1 and mARC-2) represent a novel group of Mo containing enzymes in eukaryotes. These proteins form the catalytic part of a three-component enzyme complex known to be responsible for the reductive activation of several N-hydroxylated prodrugs. No X-ray crystal structures are available for these enzymes as yet. Previous biochemical investigation by B. Wahl et al. (J. Biol. Chem. 285 (2010) 37847–37859) has revealed that two of the Mo coordination positions are occupied by sulfur atoms from a pyranopterindithiolate (molybdopterin, MPT) cofactor. In this work, we have used continuous wave and pulsed electron paramagnetic resonance (EPR) and density functional theoretical (DFT) calculations to determine the nature of remaining ligands in the Mo(V) state of the active site of mARC-2. The experiments with samples in D2O have identified the exchangeable equatorial ligand as a hydroxyl group. The experiments on samples in H217O-enriched buffer have shown the presence of a slowly exchangeable axial oxo ligand. The comparison of the experimental 1H and 17O hyperfine interactions with those calculated using DFT has shown that the remaining non-exchangeable equatorial ligand is, most likely, protein-derived, and that the possibility of an equatorial oxo ligand can be excluded. PMID:21916412

Probing the interaction of U (VI) with phosphonate-functionalized mesoporous silica using solid-state NMR spectroscopy

DOE PAGES

Uribe, Eva C.; Mason, Harris E.; Shusterman, Jennifer A.; ...

2016-05-30

The fundamental interaction of U (VI) with diethylphosphatoethyl triethoxysilane functionalized SBA-15 mesoporous silica is studied by macroscopic batch experiments and solid-state NMR spectroscopy. DPTS-functionalized silica has been shown to extract U (VI) from nitric acid solutions at or above pH 3. Extraction is dependent on pH and ionic strength. Single-pulse 31P NMR on U (VI) contacted samples revealed that U (VI)only interacts with a fraction of the ligands present on the surface. At pH 4 the U (VI) extraction capacity of the material is limited to 27–37% of the theoretical capacity, based on ligand loading. We combined single pulse 31Pmore » NMR on U (VI)-contacted samples with batch studies to measure a ligand-to-metal ratio of approximately 2 : 1 at pH 3 and 4. Batch studies and cross-polarization NMR measurements reveal that U (VI) binds to deprotonated phosphonate and/or silanol sites. We use 31P– 31P DQ-DRENAR NMR studies to compare the average dipolar coupling between phosphorus spins for both U (VI)-complexed and non-complexed ligand environments. Furthermore, these measurements reveal that U (VI) extraction is not limited by inadequate surface distribution of ligands, but rather by low stability of the surface phosphonate complex.« less

Probing the interaction of U (VI) with phosphonate-functionalized mesoporous silica using solid-state NMR spectroscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Uribe, Eva C.; Mason, Harris E.; Shusterman, Jennifer A.

The fundamental interaction of U (VI) with diethylphosphatoethyl triethoxysilane functionalized SBA-15 mesoporous silica is studied by macroscopic batch experiments and solid-state NMR spectroscopy. DPTS-functionalized silica has been shown to extract U (VI) from nitric acid solutions at or above pH 3. Extraction is dependent on pH and ionic strength. Single-pulse 31P NMR on U (VI) contacted samples revealed that U (VI)only interacts with a fraction of the ligands present on the surface. At pH 4 the U (VI) extraction capacity of the material is limited to 27–37% of the theoretical capacity, based on ligand loading. We combined single pulse 31Pmore » NMR on U (VI)-contacted samples with batch studies to measure a ligand-to-metal ratio of approximately 2 : 1 at pH 3 and 4. Batch studies and cross-polarization NMR measurements reveal that U (VI) binds to deprotonated phosphonate and/or silanol sites. We use 31P– 31P DQ-DRENAR NMR studies to compare the average dipolar coupling between phosphorus spins for both U (VI)-complexed and non-complexed ligand environments. Furthermore, these measurements reveal that U (VI) extraction is not limited by inadequate surface distribution of ligands, but rather by low stability of the surface phosphonate complex.« less

Identification of metal species by ESI-MS/MS through release of free metals from the corresponding metal-ligand complexes

PubMed Central

Tsednee, Munkhtsetseg; Huang, Yu-Chen; Chen, Yet-Ran; Yeh, Kuo-Chen

2016-01-01

Electrospray ionization-mass spectrometry (ESI-MS) is used to analyze metal species in a variety of samples. Here, we describe an application for identifying metal species by tandem mass spectrometry (ESI-MS/MS) with the release of free metals from the corresponding metal–ligand complexes. The MS/MS data were used to elucidate the possible fragmentation pathways of different metal–deoxymugineic acid (–DMA) and metal–nicotianamine (–NA) complexes and select the product ions with highest abundance that may be useful for quantitative multiple reaction monitoring. This method can be used for identifying different metal–ligand complexes, especially for metal species whose mass spectra peaks are clustered close together. Different metal–DMA/NA complexes were simultaneously identified under different physiological pH conditions with this method. We further demonstrated the application of the technique for different plant samples and with different MS instruments. PMID:27240899

Accelerated Adaptive Integration Method

PubMed Central

2015-01-01

Conformational changes that occur upon ligand binding may be too slow to observe on the time scales routinely accessible using molecular dynamics simulations. The adaptive integration method (AIM) leverages the notion that when a ligand is either fully coupled or decoupled, according to λ, barrier heights may change, making some conformational transitions more accessible at certain λ values. AIM adaptively changes the value of λ in a single simulation so that conformations sampled at one value of λ seed the conformational space sampled at another λ value. Adapting the value of λ throughout a simulation, however, does not resolve issues in sampling when barriers remain high regardless of the λ value. In this work, we introduce a new method, called Accelerated AIM (AcclAIM), in which the potential energy function is flattened at intermediate values of λ, promoting the exploration of conformational space as the ligand is decoupled from its receptor. We show, with both a simple model system (Bromocyclohexane) and the more complex biomolecule Thrombin, that AcclAIM is a promising approach to overcome high barriers in the calculation of free energies, without the need for any statistical reweighting or additional processors. PMID:24780083

Implicit Self-Esteem Decreases in Adolescence: A Cross-Sectional Study

PubMed Central

Cai, Huajian; Wu, Mingzheng; Luo, Yu L. L.; Yang, Jing

2014-01-01

Implicit self-esteem has remained an active research topic in both the areas of implicit social cognition and self-esteem in recent decades. The purpose of this study is to explore the development of implicit self-esteem in adolescents. A total of 599 adolescents from junior and senior high schools in East China participated in the study. They ranged in age from 11 to 18 years with a mean age of 14.10 (SD = 2.16). The degree of implicit self-esteem was assessed using the Implicit Association Test (IAT) with the improved D score as the index. Participants also completed the Rosenberg Self-Esteem Scale (α = 0.77). For all surveyed ages, implicit self-esteem was positively biased, all ts>8.59, all ps<0.001. The simple correlation between implicit self-esteem and age was significant, r = −.25, p = 1.0×10−10. A regression with implicit self-esteem as the criterion variable, and age, gender, and age × gender interaction as predictors further revealed the significant negative linear relationship between age and implicit self-esteem, β = −0.19, t = −3.20, p = 0.001. However, explicit self-esteem manifested a reverse “U” shape throughout adolescence. Implicit self-esteem in adolescence manifests a declining trend with increasing age, suggesting that it is sensitive to developmental or age-related changes. This finding enriches our understanding of the development of implicit social cognition. PMID:24587169

Towards an explicit account of implicit learning.

PubMed

Forkstam, Christian; Petersson, Karl Magnus

2005-08-01

The human brain supports acquisition mechanisms that can extract structural regularities implicitly from experience without the induction of an explicit model. Reber defined the process by which an individual comes to respond appropriately to the statistical structure of the input ensemble as implicit learning. He argued that the capacity to generalize to new input is based on the acquisition of abstract representations that reflect underlying structural regularities in the acquisition input. We focus this review of the implicit learning literature on studies published during 2004 and 2005. We will not review studies of repetition priming ('implicit memory'). Instead we focus on two commonly used experimental paradigms: the serial reaction time task and artificial grammar learning. Previous comprehensive reviews can be found in Seger's 1994 article and the Handbook of Implicit Learning. Emerging themes include the interaction between implicit and explicit processes, the role of the medial temporal lobe, developmental aspects of implicit learning, age-dependence, the role of sleep and consolidation. The attempts to characterize the interaction between implicit and explicit learning are promising although not well understood. The same can be said about the role of sleep and consolidation. Despite the fact that lesion studies have relatively consistently suggested that the medial temporal lobe memory system is not necessary for implicit learning, a number of functional magnetic resonance studies have reported medial temporal lobe activation in implicit learning. This issue merits further research. Finally, the clinical relevance of implicit learning remains to be determined.

Distinguishing the affective and cognitive bases of implicit attitudes to improve prediction of food choices.

PubMed

Trendel, Olivier; Werle, Carolina O C

2016-09-01

Eating behaviors largely result from automatic processes. Yet, in existing research, automatic or implicit attitudes toward food often fail to predict eating behaviors. Applying findings in cognitive neuroscience research, we propose and find that a central reason why implicit attitudes toward food are not good predictors of eating behaviors is that implicit attitudes are driven by two distinct constructs that often have diverging evaluative consequences: the automatic affective reactions to food (e.g., tastiness; the affective basis of implicit attitudes) and the automatic cognitive reactions to food (e.g., healthiness; the cognitive basis of implicit attitudes). More importantly, we find that the affective and cognitive bases of implicit attitudes directly and uniquely influence actual food choices under different conditions. While the affective basis of implicit attitude is the main driver of food choices, it is the only driver when cognitive resources during choice are limited. The cognitive basis of implicit attitudes uniquely influences food choices when cognitive resources during choice are plentiful but only for participants low in impulsivity. Researchers interested in automatic processes in eating behaviors could thus benefit by distinguishing between the affective and cognitive bases of implicit attitudes. Copyright © 2015 Elsevier Ltd. All rights reserved.

Patient-centered care, nurse work environment and implicit rationing of nursing care in Swiss acute care hospitals: A cross-sectional multi-center study.

PubMed

Bachnick, Stefanie; Ausserhofer, Dietmar; Baernholdt, Marianne; Simon, Michael

2018-05-01

Patient-centered care is a key element of high-quality healthcare and determined by individual, structural and process factors. Patient-centered care is associated with improved patient-reported, clinical and economic outcomes. However, while hospital-level characteristics influence patient-centered care, little evidence is available on the association of patient-centered care with characteristic such as the nurse work environment or implicit rationing of nursing care. The aim of this study was to describe patient-centered care in Swiss acute care hospitals and to explore the associations with nurse work environment factors and implicit rationing of nursing care. This is a sub-study of the cross-sectional multi-center "Matching Registered Nurse Services with Changing Care Demands" study. We included 123 units in 23 acute care hospitals from all three of Switzerland's language regions. The sample consisted of 2073 patients, hospitalized for at least 24 h and ≥18 years of age. From the same hospital units, 1810 registered nurses working in direct patient care were also included. Patients' perceptions of patient-centered care were assessed using four items from the Generic Short Patient Experiences Questionnaire. Nurses completed questionnaires assessing perceived staffing and resource adequacy, adjusted staffing, leadership ability and level of implicit rationing of nursing care. We applied a Generalized Linear Mixed Models for analysis including individual-level patient and nurse data aggregated to the unit level. Patients reported high levels of patient-centered care: 90% easily understood nurses, 91% felt the treatment and care were adapted for their situation, 82% received sufficient information, and 70% felt involved in treatment and care decisions. Higher staffing and resource adequacy was associated with higher levels of patient-centered care, e.g., sufficient information (β 0.638 [95%-CI: 0.30-0.98]). Higher leadership ratings were associated with sufficient information (β 0.403 [95%-CI: 0.03-0.77) and adapted treatment and care (β 0.462 [95%-CI: 0.04-0.88]). Furthermore, higher levels of implicit rationing of nursing care were associated with lower levels of patient-centered care, e.g., adapted treatment and care (β -0.912 [95%-CI: -1.50-0.33]). Our study shows a negative association between implicit rationing of nursing care and patient-centered care: i.e.the lower the level of implicit rationing of nursing care, the better patients understood nurses, felt sufficiently informed and recognized that they were receiving highly individualized treatment. To improve patient-centered care, the nurse work environment and the level of implicit rationing of nursing care should be taken into consideration. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Sampling Design of the China Family Panel Studies (CFPS)

PubMed Central

Xie, Yu; Lu, Ping

2018-01-01

The China Family Panel Studies (CFPS) is an on-going, nearly nationwide, comprehensive, longitudinal social survey that is intended to serve research needs on a large variety of social phenomena in contemporary China. In this paper, we describe the sampling design of the CFPS sample for its 2010 baseline survey and methods for constructing weights to adjust for sampling design and survey nonresponses. Specifically, the CFPS used a multi-stage probability strategy to reduce operation costs and implicit stratification to increase efficiency. Respondents were oversampled in five provinces or administrative equivalents for regional comparisons. We provide operation details for both sampling and weights construction. PMID:29854418

Implicit Associations and Explicit Expectancies toward Cannabis in Heavy Cannabis Users and Controls

PubMed Central

Beraha, Esther M.; Cousijn, Janna; Hermanides, Elisa; Goudriaan, Anna E.; Wiers, Reinout W.

2013-01-01

Cognitive biases, including implicit memory associations are thought to play an important role in the development of addictive behaviors. The aim of the present study was to investigate implicit affective memory associations in heavy cannabis users. Implicit positive-arousal, sedation, and negative associations toward cannabis were measured with three Single Category Implicit Association Tests (SC-IAT’s) and compared between 59 heavy cannabis users and 89 controls. Moreover, we investigated the relationship between these implicit affective associations and explicit expectancies, subjective craving, cannabis use, and cannabis related problems. Results show that heavy cannabis users had stronger implicit positive-arousal associations but weaker implicit negative associations toward cannabis compared to controls. Moreover, heavy cannabis users had stronger sedation but weaker negative explicit expectancies toward cannabis compared to controls. Within heavy cannabis users, more cannabis use was associated with stronger implicit negative associations whereas more cannabis use related problems was associated with stronger explicit negative expectancies, decreasing the overall difference on negative associations between cannabis users and controls. No other associations were observed between implicit associations, explicit expectancies, measures of cannabis use, cannabis use related problems, or subjective craving. These findings indicate that, in contrast to other substances of abuse like alcohol and tobacco, the relationship between implicit associations and cannabis use appears to be weak in heavy cannabis users. PMID:23801968

Implicit and explicit ethnocentrism: revisiting the ideologies of prejudice.

PubMed

Cunningham, William A; Nezlek, John B; Banaji, Mahzarin R

2004-10-01

Two studies investigated relationships among individual differences in implicit and explicit prejudice, right-wing ideology, and rigidity in thinking. The first study examined these relationships focusing on White Americans' prejudice toward Black Americans. The second study provided the first test of implicit ethnocentrism and its relationship to explicit ethnocentrism by studying the relationship between attitudes toward five social groups. Factor analyses found support for both implicit and explicit ethnocentrism. In both studies, mean explicit attitudes toward out groups were positive, whereas implicit attitudes were negative, suggesting that implicit and explicit prejudices are distinct; however, in both studies, implicit and explicit attitudes were related (r = .37, .47). Latent variable modeling indicates a simple structure within this ethnocentric system, with variables organized in order of specificity. These results lead to the conclusion that (a) implicit ethnocentrism exists and (b) it is related to and distinct from explicit ethnocentrism.

Hooked on a feeling: affective anti-smoking messages are more effective than cognitive messages at changing implicit evaluations of smoking

PubMed Central

Smith, Colin Tucker; De Houwer, Jan

2015-01-01

Because implicit evaluations are thought to underlie many aspects of behavior, researchers have started looking for ways to change them. We examine whether and when persuasive messages alter strongly held implicit evaluations of smoking. In smokers, an affective anti-smoking message led to more negative implicit evaluations on four different implicit measures as compared to a cognitive anti-smoking message which seemed to backfire. Additional analyses suggested that the observed effects were mediated by the feelings and emotions raised by the messages. In non-smokers, both the affective and cognitive message engendered slightly more negative implicit evaluations. We conclude that persuasive messages change implicit evaluations in a way that depends on properties of the message and of the participant. Thus, our data open new avenues for research directed at tailoring persuasive messages to change implicit evaluations. PMID:26557099

Hooked on a feeling: affective anti-smoking messages are more effective than cognitive messages at changing implicit evaluations of smoking.

PubMed

Smith, Colin Tucker; De Houwer, Jan

2015-01-01

Because implicit evaluations are thought to underlie many aspects of behavior, researchers have started looking for ways to change them. We examine whether and when persuasive messages alter strongly held implicit evaluations of smoking. In smokers, an affective anti-smoking message led to more negative implicit evaluations on four different implicit measures as compared to a cognitive anti-smoking message which seemed to backfire. Additional analyses suggested that the observed effects were mediated by the feelings and emotions raised by the messages. In non-smokers, both the affective and cognitive message engendered slightly more negative implicit evaluations. We conclude that persuasive messages change implicit evaluations in a way that depends on properties of the message and of the participant. Thus, our data open new avenues for research directed at tailoring persuasive messages to change implicit evaluations.

Adults' implicit associations to infant positive and negative acoustic cues: Moderation by empathy and gender.

PubMed

Senese, Vincenzo Paolo; Venuti, Paola; Giordano, Francesca; Napolitano, Maria; Esposito, Gianluca; Bornstein, Marc H

2017-09-01

In this study a novel auditory version of the Single Category Implicit Association Test (SC-IAT-A) was developed to investigate (a) the valence of adults' associations to infant cries and laughs, (b) moderation of implicit associations by gender and empathy, and (c) the robustness of implicit associations controlling for auditory sensitivity. Eighty adults (50% females) were administered two SC-IAT-As, the Empathy Quotient, and the Weinstein Noise Sensitivity Scale. Adults showed positive implicit associations to infant laugh and negative ones to infant cry; only the implicit associations with the infant laugh were negatively related to empathy scores, and no gender differences were observed. Finally, implicit associations to infant cry were affected by noise sensitivity. The SC-IAT-A is useful to evaluate the valence of implicit reactions to infant auditory cues and could provide fresh insights into understanding processes that regulate the quality of adult-infant relationships.

Self-Regulation and Implicit Attitudes Toward Physical Activity Influence Exercise Behavior.

PubMed

Padin, Avelina C; Emery, Charles F; Vasey, Michael; Kiecolt-Glaser, Janice K

2017-08-01

Dual-process models of health behavior posit that implicit and explicit attitudes independently drive healthy behaviors. Prior evidence indicates that implicit attitudes may be related to weekly physical activity (PA) levels, but the extent to which self-regulation attenuates this link remains unknown. This study examined the associations between implicit attitudes and self-reported PA during leisure time among 150 highly active young adults and evaluated the extent to which effortful control (one aspect of self-regulation) moderated this relationship. Results indicated that implicit attitudes toward exercise were unrelated to average workout length among individuals with higher effortful control. However, those with lower effortful control and more negative implicit attitudes reported shorter average exercise sessions compared with those with more positive attitudes. Implicit and explicit attitudes were unrelated to total weekly PA. A combination of poorer self-regulation and negative implicit attitudes may leave individuals vulnerable to mental and physical health consequences of low PA.

Understanding the kinetics of ligand binding to globins with molecular dynamics simulations: the necessity of multiple state models.

PubMed

Estarellas Martin, Carolina; Seira Castan, Constantí; Luque Garriga, F Javier; Bidon-Chanal Badia, Axel

2015-10-01

Residue conformational changes and internal cavity migration processes play a key role in regulating the kinetics of ligand migration and binding events in globins. Molecular dynamics simulations have demonstrated their value in the study of these processes in different haemoglobins, but derivation of kinetic data demands the use of more complex techniques like enhanced sampling molecular dynamics methods. This review discusses the different methodologies that are currently applied to study the ligand migration process in globins and highlight those specially developed to derive kinetic data. Copyright © 2015 Elsevier Ltd. All rights reserved.

Prediction of Stereochemistry using Q2MM

PubMed Central

2016-01-01

Conspectus The standard method of screening ligands for selectivity in asymmetric, transition metal-catalyzed reactions requires experimental testing of hundreds of ligands from ligand libraries. This “trial and error” process is costly in terms of time as well as resources and, in general, is scientifically and intellectually unsatisfying as it reveals little about the underlying mechanism behind the selectivity. The accurate computational prediction of stereoselectivity in enantioselective catalysis requires adequate conformational sampling of the selectivity-determining transition state but has to be fast enough to compete with experimental screening techniques to be useful for the synthetic chemist. Although electronic structure calculations are accurate and general, they are too slow to allow for sampling or fast screening of ligand libraries. The combined requirements can be fulfilled by using appropriately fitted transition state force fields (TSFFs) that represent the transition state as a minimum and allow fast conformational sampling using Monte Carlo. Quantum-guided molecular mechanics (Q2MM) is an automated force field parametrization method that generates accurate, reaction-specific TSFFs by fitting the functional form of an arbitrary force field using only electronic structure calculations by minimization of an objective function. A key feature that distinguishes the Q2MM method from many other automated parametrization procedures is the use of the Hessian matrix in addition to geometric parameters and relative energies. This alleviates the known problems of overfitting of TSFFs. After validation of the TSFF by comparison to electronic structure results for a test set and available experimental data, the stereoselectivity of a reaction can be calculated by summation over the Boltzman-averaged relative energies of the conformations leading to the different stereoisomers. The Q2MM method has been applied successfully to perform virtual ligand screens on a range of transition metal-catalyzed reactions that are important from both an industrial and an academic perspective. In this Account, we provide an overview of the continued improvement of the prediction of stereochemistry using Q2MM-derived TSFFs using four examples from different stages of development: (i) Pd-catalyzed allylation, (ii) OsO4-catalyzed asymmetric dihydroxylation (AD) of alkenes, (iii) Rh-catalyzed hydrogenation of enamides, and (iv) Ru-catalyzed hydrogenation of ketones. In the current form, correlation coefficients of 0.8–0.9 between calculated and experimental ee values are typical for a wide range of substrate–ligand combinations, and suitable ligands can be predicted for a given substrate with ∼80% accuracy. Although the generation of a TSFF requires an initial effort and will therefore be most useful for widely used reactions that require frequent screening campaigns, the method allows for a rapid virtual screen of large ligand libraries to focus experimental efforts on the most promising substrate–ligand combinations. PMID:27064579

Mechanistic pathways of recognition of a solvent-inaccessible cavity of protein by a ligand

NASA Astrophysics Data System (ADS)

Mondal, Jagannath; Pandit, Subhendu; Dandekar, Bhupendra; Vallurupalli, Pramodh

One of the puzzling questions in the realm of protein-ligand recognition is how a solvent-inaccessible hydrophobic cavity of a protein gets recognized by a ligand. We address the topic by simulating, for the first time, the complete binding process of benzene from aqueous media to the well-known buried cavity of L99A T4 Lysozyme at an atomistic resolution. Our multiple unbiased microsecond-long trajectories, which were completely blind to the location of target binding site, are able to unequivocally identify the kinetic pathways along which benzene molecule meanders across the solvent and protein and ultimately spontaneously recognizes the deeply buried cavity of L99A T4 Lysozyme at an accurate precision. Our simulation, combined with analysis based on markov state model and free energy calculation, reveals that there are more than one distinct ligand binding pathways. Intriguingly, each of the identified pathways involves the transient opening of a channel of the protein prior to ligand binding. The work will also decipher rich mechanistic details on unbinding kinetics of the ligand as obtained from enhanced sampling techniques.

Using the Implicit Association Test and the Implicit Relational Assessment Procedure to Measure Attitudes toward Meat and Vegetables in Vegetarians and Meat-Eaters

ERIC Educational Resources Information Center

Barnes-Holmes, Dermot; Murtagh, Louise; Barnes-Holmes, Yvonne; Stewart, Ian

2010-01-01

The current study aimed to assess the implicit attitudes of vegetarians and non-vegetarians towards meat and vegetables, using the Implicit Association Test (IAT) and the Implicit Relational Assessment Procedure (IRAP). Both measures involved asking participants to respond, under time pressure, to pictures of meat or vegetables as either positive…

The Movable Type Method Applied to Protein-Ligand Binding.

PubMed

Zheng, Zheng; Ucisik, Melek N; Merz, Kenneth M

2013-12-10

Accurately computing the free energy for biological processes like protein folding or protein-ligand association remains a challenging problem. Both describing the complex intermolecular forces involved and sampling the requisite configuration space make understanding these processes innately difficult. Herein, we address the sampling problem using a novel methodology we term "movable type". Conceptually it can be understood by analogy with the evolution of printing and, hence, the name movable type. For example, a common approach to the study of protein-ligand complexation involves taking a database of intact drug-like molecules and exhaustively docking them into a binding pocket. This is reminiscent of early woodblock printing where each page had to be laboriously created prior to printing a book. However, printing evolved to an approach where a database of symbols (letters, numerals, etc.) was created and then assembled using a movable type system, which allowed for the creation of all possible combinations of symbols on a given page, thereby, revolutionizing the dissemination of knowledge. Our movable type (MT) method involves the identification of all atom pairs seen in protein-ligand complexes and then creating two databases: one with their associated pairwise distant dependent energies and another associated with the probability of how these pairs can combine in terms of bonds, angles, dihedrals and non-bonded interactions. Combining these two databases coupled with the principles of statistical mechanics allows us to accurately estimate binding free energies as well as the pose of a ligand in a receptor. This method, by its mathematical construction, samples all of configuration space of a selected region (the protein active site here) in one shot without resorting to brute force sampling schemes involving Monte Carlo, genetic algorithms or molecular dynamics simulations making the methodology extremely efficient. Importantly, this method explores the free energy surface eliminating the need to estimate the enthalpy and entropy components individually. Finally, low free energy structures can be obtained via a free energy minimization procedure yielding all low free energy poses on a given free energy surface. Besides revolutionizing the protein-ligand docking and scoring problem this approach can be utilized in a wide range of applications in computational biology which involve the computation of free energies for systems with extensive phase spaces including protein folding, protein-protein docking and protein design.

I trust it, but I don't know why: effects of implicit attitudes toward automation on trust in an automated system.

PubMed

Merritt, Stephanie M; Heimbaugh, Heather; LaChapell, Jennifer; Lee, Deborah

2013-06-01

This study is the first to examine the influence of implicit attitudes toward automation on users' trust in automation. Past empirical work has examined explicit (conscious) influences on user level of trust in automation but has not yet measured implicit influences. We examine concurrent effects of explicit propensity to trust machines and implicit attitudes toward automation on trust in an automated system. We examine differential impacts of each under varying automation performance conditions (clearly good, ambiguous, clearly poor). Participants completed both a self-report measure of propensity to trust and an Implicit Association Test measuring implicit attitude toward automation, then performed an X-ray screening task. Automation performance was manipulated within-subjects by varying the number and obviousness of errors. Explicit propensity to trust and implicit attitude toward automation did not significantly correlate. When the automation's performance was ambiguous, implicit attitude significantly affected automation trust, and its relationship with propensity to trust was additive: Increments in either were related to increases in trust. When errors were obvious, a significant interaction between the implicit and explicit measures was found, with those high in both having higher trust. Implicit attitudes have important implications for automation trust. Users may not be able to accurately report why they experience a given level of trust. To understand why users trust or fail to trust automation, measurements of implicit and explicit predictors may be necessary. Furthermore, implicit attitude toward automation might be used as a lever to effectively calibrate trust.

Using the Implicit Association Test to Assess Children's Implicit Attitudes toward Smoking.

PubMed

Andrews, Judy A; Hampson, Sarah E; Greenwald, Anthony G; Gordon, Judith; Widdop, Chris

2010-09-01

The development and psychometric properties of an Implicit Association Test (IAT) measuring implicit attitude toward smoking among fifth grade children were described. The IAT with "sweets" as the contrast category resulted in higher correlations with explicit attitudes than did the IAT with "healthy foods" as the contrast category. Children with family members who smoked (versus non-smoking) and children who were high in sensation seeking (versus low) had a significantly more favorable implicit attitude toward smoking. Further, implicit attitudes became less favorable after engaging in tobacco prevention activities targeting risk perceptions of addiction. Results support the reliability and validity of this version of the IAT and illustrate its usefulness in assessing young children's implicit attitude toward smoking.

Using the Implicit Association Test to Assess Children's Implicit Attitudes toward Smoking

PubMed Central

Andrews, Judy A.; Hampson, Sarah E.; Greenwald, Anthony G.; Gordon, Judith; Widdop, Chris

2009-01-01

The development and psychometric properties of an Implicit Association Test (IAT) measuring implicit attitude toward smoking among fifth grade children were described. The IAT with “sweets” as the contrast category resulted in higher correlations with explicit attitudes than did the IAT with “healthy foods” as the contrast category. Children with family members who smoked (versus non-smoking) and children who were high in sensation seeking (versus low) had a significantly more favorable implicit attitude toward smoking. Further, implicit attitudes became less favorable after engaging in tobacco prevention activities targeting risk perceptions of addiction. Results support the reliability and validity of this version of the IAT and illustrate its usefulness in assessing young children's implicit attitude toward smoking. PMID:21566676

Power effects on implicit prejudice and stereotyping: The role of intergroup face processing.

PubMed

Schmid, Petra C; Amodio, David M

2017-04-01

Power is thought to increase discrimination toward subordinate groups, yet its effect on different forms of implicit bias remains unclear. We tested whether power enhances implicit racial stereotyping, in addition to implicit prejudice (i.e., evaluative associations), and examined the effect of power on the automatic processing of faces during implicit tasks. Study 1 showed that manipulated high power increased both forms of implicit bias, relative to low power. Using a neural index of visual face processing (the N170 component of the ERP), Study 2 revealed that power affected the encoding of White ingroup vs. Black outgroup faces. Whereas high power increased the relative processing of outgroup faces during evaluative judgments in the prejudice task, it decreased the relative processing of outgroup faces during stereotype trait judgments. An indirect effect of power on implicit prejudice through enhanced processing of outgroup versus ingroup faces suggested a potential link between face processing and implicit bias. Together, these findings demonstrate that power can affect implicit prejudice and stereotyping as well as early processing of racial ingroup and outgroup faces.

Implicit Attitudes toward the Self Over Time in Chinese Undergraduates

PubMed Central

Yang, Qing; Zhao, Yufang; Guan, Lili; Huang, Xiting

2017-01-01

Although the explicit attitudes of Chinese people toward the self over time are known (i.e., past = present < future), little is known about their implicit attitudes. Two studies were conducted to measure the implicit subjective temporal trajectory (STT) of Chinese undergraduates. Study 1 used a Go/No-go association task to measure participants’ implicit attitudes toward their past, present, and future selves. The obtained implicit STT was different from the explicit pattern found in former research. It showed that the future self was viewed to be identical to the present self and participants implicitly evaluated their present self as better than the past self. Since this comparison of the past and present selves suggested a cultural difference, we aimed to replicate this finding in Study 2. Using an implicit association test, we again found that the present self was more easily associated with positive valence than the past self. Overall, both studies reveal an implicitly inclining-flat STT (i.e., past < present = future) for Chinese undergraduates. Implications of this difference in explicit-implicit measures and the cultural differences of temporal self appraisals are discussed. PMID:29163291

Implicit Motives and Men’s Perceived Constraint in Fatherhood

PubMed Central

Ruppen, Jessica; Waldvogel, Patricia; Ehlert, Ulrike

2016-01-01

Research shows that implicit motives influence social relationships. However, little is known about their role in fatherhood and, particularly, how men experience their paternal role. Therefore, this study examined the association of implicit motives and fathers’ perceived constraint due to fatherhood. Furthermore, we explored their relation to fathers’ life satisfaction. Participants were fathers with biological children (N = 276). They were asked to write picture stories, which were then coded for implicit affiliation and power motives. Perceived constraint and life satisfaction were assessed on a visual analog scale. A higher implicit need for affiliation was significantly associated with lower perceived constraint, whereas the implicit need for power had the opposite effect. Perceived constraint had a negative influence on life satisfaction. Structural equation modeling revealed significant indirect effects of implicit affiliation and power motives on life satisfaction mediated by perceived constraint. Our findings indicate that men with a higher implicit need for affiliation experience less constraint due to fatherhood, resulting in higher life satisfaction. The implicit need for power, however, results in more perceived constraint and is related to decreased life satisfaction. PMID:27933023

Development of a Charge-Implicit ReaxFF Potential for Hydrocarbon Systems.

PubMed

Kański, Michał; Maciążek, Dawid; Postawa, Zbigniew; Ashraf, Chowdhury M; van Duin, Adri C T; Garrison, Barbara J

2018-01-18

Molecular dynamics (MD) simulations continue to make important contributions to understanding chemical and physical processes. Concomitant with the growth of MD simulations is the need to have interaction potentials that both represent the chemistry of the system and are computationally efficient. We propose a modification to the ReaxFF potential for carbon and hydrogen that eliminates the time-consuming charge equilibration, eliminates the acknowledged flaws of the electronegativity equalization method, includes an expanded training set for condensed phases, has a repulsive wall for simulations of energetic particle bombardment, and is compatible with the LAMMPS code. This charge-implicit ReaxFF potential is five times faster than the conventional ReaxFF potential for a simulation of keV particle bombardment with a sample size of over 800 000 atoms.

Colloidal 3-Mercaptopropionic Acid Capped Lead Sulfide Quantum Dots in a Low Boiling Point Solvent.

PubMed

Reinhart, Chase C; Johansson, Erik

2017-04-26

Colloidal 3-mercaptopropionic acid (3-MPA) capped lead sulfide quantum dots were prepared in a variety of organic solvents stabilized with a quaternary ammonium halide salt. The stabilized colloids' optical properties were studied through optical absorption and emission spectroscopy and found to be dependent on both the concentration of a new ligand and stabilizer, and sample age. Nanocrystal ligand chemistry was studied through a combination of 1 H NMR and two-dimensional Nuclear Overhauser Effect Spectroscopy (NOESY) which revealed full displacement of the original oleate ligand to form a dynamically exchanging ligand shell. The colloids were studied optically and via NMR as they aged and revealed a quantitative conversion of monomeric 3-mercaptopropionic acid to its dimer, dithiodipropionic acid (dTdPA).

Implicit Depression and Hopelessness in Remitted Depressed Individuals

PubMed Central

Meites, Tiffany M.; Deveney, Christen M.; Steele, Katherine T.; Holmes, Avram J.; Pizzagalli, Diego A.

2008-01-01

Cognitive theories of depression posit that automatically activated cognitive schemas, including negative thoughts about the self and the future, predispose individuals to develop depressive disorders. However, prior research has largely examined these constructs using explicit tests in currently depressed individuals. Using the Implicit Association Test (IAT), the present study examined automatic associations between the self and mood state (“depression IAT”) and between the future and mood state (“hopelessness IAT”) before and after a negative mood induction in 19 remitted depressed individuals and 23 healthy controls. In the depression IAT, remitted depressed participants exhibited an overall lower tendency to associate themselves with happiness relative to the healthy controls before the mood induction. Control, but not remitted depressed, participants’ automatic associations between the self and happiness diminished following the mood induction. Contrary to our hypotheses, no significant findings emerged when considering the hopelessness IAT. Consistent with prior studies, no significant correlations emerged between implicit and explicit biases, suggesting that these measures probe different processes. Results extend prior IAT research by documenting the presence of a reduced tendency to associate the self with happiness in a sample at increased risk for depression. PMID:18692169

Incidental Learning of Melodic Structure of North Indian Music.

PubMed

Rohrmeier, Martin; Widdess, Richard

2017-07-01

Musical knowledge is largely implicit. It is acquired without awareness of its complex rules, through interaction with a large number of samples during musical enculturation. Whereas several studies explored implicit learning of mostly abstract and less ecologically valid features of Western music, very little work has been done with respect to ecologically valid stimuli as well as non-Western music. The present study investigated implicit learning of modal melodic features in North Indian classical music in a realistic and ecologically valid way. It employed a cross-grammar design, using melodic materials from two modes (rāgas) that use the same scale. Findings indicated that Western participants unfamiliar with Indian music incidentally learned to identify distinctive features of each mode. Confidence ratings suggest that participants' performance was consistently correlated with confidence, indicating that they became aware of whether they were right in their responses; that is, they possessed explicit judgment knowledge. Altogether our findings show incidental learning in a realistic ecologically valid context during only a very short exposure, they provide evidence that incidental learning constitutes a powerful mechanism that plays a fundamental role in musical acquisition. Copyright © 2016 Cognitive Science Society, Inc.

What changes in cognitive therapy for depression? An examination of cognitive therapy skills and maladaptive beliefs.

PubMed

Adler, Abby D; Strunk, Daniel R; Fazio, Russell H

2015-01-01

This study examined effortful cognitive skills and underlying maladaptive beliefs among patients treated with cognitive therapy (CT) for depression. Depressed patients (n=44) completed cognitive measures before and after 16 weeks of CT. Measures included an assessment of CT skills (Ways of Responding Scale; WOR), an implicit test of maladaptive beliefs (Implicit Association Test; IAT), and a self-report questionnaire of maladaptive beliefs (Dysfunctional Attitude Scale; DAS). A matched sample of never-depressed participants (n=44) also completed study measures. Prior to treatment, depressed patients endorsed significantly more undesirable cognitions on the WOR, IAT, and DAS compared with never-depressed participants. Patients displayed improvement on the WOR and DAS over the course of treatment, but showed no change on the IAT. Additionally, improvements on the WOR and DAS were each related to greater reductions in depressive symptoms. Results suggest that the degree of symptom reduction among patients participating in CT is related to changes in patients' acquisition of coping skills requiring deliberate efforts and reflective thought, but not related to reduced endorsement of implicitly assessed maladaptive beliefs. Copyright © 2014. Published by Elsevier Ltd.

A Paradigm to Assess Implicit Attitudes towards God: The Positive/Negative God Associations Task.

PubMed

Pirutinsky, Steven; Carp, Sean; Rosmarin, David H

2017-02-01

Psychological research on the relationship between spirituality/religion and mental health has grown considerably over the past several decades and now constitutes a sizable body of scholarship. Among dimensions of S/R, positive beliefs about God have been significantly related to better mental health outcomes, and conversely negative beliefs about God are generally associated with more distress. However, prior research on this topic has relied heavily upon self-report Likert-type scales, which are vulnerable to self-report biases and measure only explicit cognitive processes. In this study, we developed and validated an implicit social cognition task, the Positive/Negative God Go/No-go Association Task (PNG-GNAT), for use in psychological research on spirituality and religion (S/R). Preliminary evidence in a large sample (N = 381) suggests that the PNG-GNAT demonstrates internal consistency, test-retest and split-half reliability, and concurrent evidence of validity. Further, our results suggest that PNG-GNAT scores represent different underlying dimensions of S/R than explicit self-report measures, and incrementally predict mental health above and beyond self-report assessment. The PNG-GNAT appears to be an effective tool for measuring implicit positive/negative beliefs about God.

Messages promoting genetic modification of crops in the context of climate change: Evidence for psychological reactance.

PubMed

Lu, Hang; McComas, Katherine A; Besley, John C

2017-01-01

Genetic modification (GM) of crops and climate change are arguably two of today's most challenging science communication issues. Increasingly, these two issues are connected in messages proposing GM as a viable option for ensuring global food security threatened by climate change. This study examines the effects of messages promoting the benefits of GM in the context of climate change. Further, it examines whether explicit reference to "climate change," or "global warming" in a GM message results in different effects than each other, or an implicit climate reference. An online sample of U.S. participants (N = 1050) were randomly assigned to one of four conditions: "climate change" cue, "global warming" cue, implicit cue, or control (no message). Generally speaking, framing GM crops as a way to help ensure global food security proved to be an effective messaging strategy in increasing positive attitudes toward GM. In addition, the implicit cue condition led to liberals having more positive attitudes and behavioral intentions toward GM than the "climate change" cue condition, an effect mediated by message evaluations. Copyright © 2016 Elsevier Ltd. All rights reserved.

Influence of smoking cues in movies on children's beliefs about smoking.

PubMed

Lochbuehler, Kirsten; Sargent, James D; Scholte, Ron H J; Pieters, Sara; Engels, Rutger C M E

2012-08-01

Experimental research has revealed that short exposure to movie smoking affects beliefs about smoking in adolescents. In this study, we tested that association in children. In 2 experiments, participants were exposed to either a cartoon or family-oriented movie and randomly assigned to 20-minute segments with or without smoking characters. Data collection took place at elementary schools. A total of 101 children (8-10 years; 47.5% boys) were exposed to a cartoon, and in a second experiment, 105 children (8-11 years; 56.2% boys) were exposed to a family-oriented movie. Beliefs about smoking (assessed by questionnaire) and implicit associations toward smoking (single target implicit association task) were assessed after watching the movie. The majority of both samples of children viewed smoking unfavorably. Exposure to movie smoking had no effect on implicit associations toward smoking when experiments were analyzed separately or if the results were combined. For smoking beliefs, effects were again small and only statistically significant for social norms regarding smoking. Short-term exposure to smoking in cartoon and family-oriented movies had little immediate impact on beliefs about smoking in preadolescent children, but a significant cumulative impact on norms cannot be ruled out.

Towards Standardization in Terminal Ballistics Testing: Velocity Representation

DTIC Science & Technology

1976-01-01

d vd vr does not exist at vV, it is true that -. Also avs rd s t d v s approximates...29 3b. Sample of plotter output: v versus v s -r.. ....... .. 30s S 3c. Sample of plotter output: v /vs versus vr/avs. ...... 31 I ’ i Li- Preceding...implicit in sets of ( v s , v r) data. A form is proposed as being sufficiently simple and versatile to usefully and realistically model

Gaussian Accelerated Molecular Dynamics: Unconstrained Enhanced Sampling and Free Energy Calculation.

PubMed

Miao, Yinglong; Feher, Victoria A; McCammon, J Andrew

2015-08-11

A Gaussian accelerated molecular dynamics (GaMD) approach for simultaneous enhanced sampling and free energy calculation of biomolecules is presented. By constructing a boost potential that follows Gaussian distribution, accurate reweighting of the GaMD simulations is achieved using cumulant expansion to the second order. Here, GaMD is demonstrated on three biomolecular model systems: alanine dipeptide, chignolin folding, and ligand binding to the T4-lysozyme. Without the need to set predefined reaction coordinates, GaMD enables unconstrained enhanced sampling of these biomolecules. Furthermore, the free energy profiles obtained from reweighting of the GaMD simulations allow us to identify distinct low-energy states of the biomolecules and characterize the protein-folding and ligand-binding pathways quantitatively.

Gaussian Accelerated Molecular Dynamics: Unconstrained Enhanced Sampling and Free Energy Calculation

PubMed Central

2016-01-01

A Gaussian accelerated molecular dynamics (GaMD) approach for simultaneous enhanced sampling and free energy calculation of biomolecules is presented. By constructing a boost potential that follows Gaussian distribution, accurate reweighting of the GaMD simulations is achieved using cumulant expansion to the second order. Here, GaMD is demonstrated on three biomolecular model systems: alanine dipeptide, chignolin folding, and ligand binding to the T4-lysozyme. Without the need to set predefined reaction coordinates, GaMD enables unconstrained enhanced sampling of these biomolecules. Furthermore, the free energy profiles obtained from reweighting of the GaMD simulations allow us to identify distinct low-energy states of the biomolecules and characterize the protein-folding and ligand-binding pathways quantitatively. PMID:26300708

Implicit attitudes towards homosexuality: reliability, validity, and controllability of the IAT.

PubMed

Banse, R; Seise, J; Zerbes, N

2001-01-01

Two experiments were conducted to investigate the psychometric properties of an Implicit Association Test (IAT; Greenwald, McGhee, & Schwartz, 1998) that was adapted to measure implicit attitudes towards homosexuality. In a first experiment, the validity of the Homosexuality-IAT was tested using a known group approach. Implicit and explicit attitudes were assessed in heterosexual and homosexual men and women (N = 101). The results provided compelling evidence for the convergent and discriminant validity of the Homosexuality-IAT as a measure of implicit attitudes. No evidence was found for two alternative explanations of IAT effects (familiarity with stimulus material and stereotype knowledge). The internal consistency of IAT scores was satisfactory (alpha s > .80), but retest correlations were lower. In a second experiment (N = 79) it was shown that uninformed participants were able to fake positive explicit but not implicit attitudes. Discrepancies between implicit and explicit attitudes towards homosexuality could be partially accounted for by individual differences in the motivation to control prejudiced behavior, thus providing independent evidence for the validity of the implicit attitude measure. Neither explicit nor implicit attitudes could be changed by persuasive messages. The results of both experiments are interpreted as evidence for a single construct account of implicit and explicit attitudes towards homosexuality.

Effects of brief mindful acceptance induction on implicit dysfunctional attitudes and concordance between implicit and explicit dysfunctional attitudes.

PubMed

Keng, Shian-Ling; Seah, Stanley T H; Tong, Eddie M W; Smoski, Moria

2016-08-01

Mindfulness-based interventions have been shown to be effective in alleviating depressive symptoms. While much work has examined the effects of mindfulness training on subjective symptoms and experiences, and less is known regarding whether mindfulness training may alter relatively uncontrollable cognitive processes associated with depressed mood, particularly implicit dysfunctional attitudes. The present study examined the effects of a brief mindful acceptance induction on implicit dysfunctional attitudes and degree of concordance between implicit and explicit dysfunctional attitudes in the context of sad mood. A total of 79 adult participants with elevated depressive symptoms underwent an autobiographical mood induction procedure before being randomly assigned to mindful acceptance or thought wandering inductions. Results showed that the effect of mindful acceptance on implicit dysfunctional attitude was significantly moderated by trait mindfulness. Participants high on trait mindfulness demonstrated significant improvements in implicit dysfunctional attitudes following the mindful acceptance induction. Those low on trait mindfulness demonstrated significantly worse implicit dysfunctional attitudes following the induction. Significantly greater levels of concordance between implicit and explicit dysfunctional attitudes were observed in the mindful acceptance condition versus the thought wandering condition. The findings highlight changes in implicit dysfunctional attitudes and improvements in self-concordance as two potential mechanisms underlying the effects of mindfulness-based interventions. Copyright © 2016 Elsevier Ltd. All rights reserved.

Sex Differences in Arithmetical Performance Scores: Central Tendency and Variability

ERIC Educational Resources Information Center

Martens, R.; Hurks, P. P. M.; Meijs, C.; Wassenberg, R.; Jolles, J.

2011-01-01

The present study aimed to analyze sex differences in arithmetical performance in a large-scale sample of 390 children (193 boys) frequenting grades 1-9. Past research in this field has focused primarily on average performance, implicitly assuming homogeneity of variance, for which support is scarce. This article examined sex differences in…

The Gender Division of Labor in Two-Earner Marriages: Dimensions of Variability and Change.

ERIC Educational Resources Information Center

Ferree, Myra Marx

1991-01-01

Examined data drawn from representative sample survey of two-earner households (n=382 couples) on division of domestic labor. Concludes that implicitly and explicitly gendered expectations that both husbands and wives bring to thinking about housework play significant role in shaping degree of egalitarianism in practice. (Author/NB)

Developing Academic Identities: Persuasive Writing as a Tool to Strengthen Emergent Academic Identities

ERIC Educational Resources Information Center

Carbone, Paula M.; Orellana, Marjorie Faulstich

2010-01-01

This paper examines how writing samples produced by middle school students reveal their emerging academic identities through their rhetorical choices in writing. Analyses of two texts produced by each student revealed students' implicit understandings of the requirements of academic voice. Through comparisons of each student's texts, strategies…

Representations of Science within Children's Trade Books

ERIC Educational Resources Information Center

Ford, Danielle J.

2006-01-01

The use of trade books in science instruction, particularly in the elementary and middle school grades, invites scrutiny into the ways in which trade books represent science and its practitioners to learners. Forty-four trade books were examined for their explicit and implicit representations of science. The majority of the sample was comprised of…

Exposure to Violent Video Games Increases Automatic Aggressiveness

ERIC Educational Resources Information Center

Uhlmann, Eric; Swanson, Jane

2004-01-01

The effects of exposure to violent video games on automatic associations with the self were investigated in a sample of 121 students. Playing the violent video game Doom led participants to associate themselves with aggressive traits and actions on the Implicit Association Test. In addition, self-reported prior exposure to violent video games…

Cognitive Processes Underlying Women's Risk Judgments: Associations with Sexual Victimization History and Rape Myth Acceptance

ERIC Educational Resources Information Center

Yeater, Elizabeth A.; Treat, Teresa A.; Viken, Richard J.; McFall, Richard M.

2010-01-01

Objective: This study evaluated the effects of sexual victimization history, rape myth acceptance, implicit attention, and recent learning on the cognitive processes underlying undergraduate women's explicit risk judgments. Method: Participants were 194 undergraduate women between 18 and 24 years of age. The sample was ethnically diverse and…

Modeling the temperature-dependent peptide vibrational spectra based on implicit-solvent model and enhance sampling technique

NASA Astrophysics Data System (ADS)

Tianmin, Wu; Tianjun, Wang; Xian, Chen; Bin, Fang; Ruiting, Zhang; Wei, Zhuang

2016-01-01

We herein review our studies on simulating the thermal unfolding Fourier transform infrared and two-dimensional infrared spectra of peptides. The peptide-water configuration ensembles, required forspectrum modeling, aregenerated at a series of temperatures using the GBOBC implicit solvent model and the integrated tempering sampling technique. The fluctuating vibrational Hamiltonians of the amide I vibrational band are constructed using the Frenkel exciton model. The signals are calculated using nonlinear exciton propagation. The simulated spectral features such as the intensity and ellipticity are consistent with the experimental observations. Comparing the signals for two beta-hairpin polypeptides with similar structures suggests that this technique is sensitive to peptide folding landscapes. Project supported by the National Natural Science Foundation of China (Grant No. 21203178), the National Natural Science Foundation of China (Grant No. 21373201), the National Natural Science Foundation of China (Grant No. 21433014), the Science and Technological Ministry of China (Grant No. 2011YQ09000505), and “Strategic Priority Research Program” of the Chinese Academy of Sciences (Grant Nos. XDB10040304 and XDB100202002).

County-level racial prejudice and the black-white gap in infant health outcomes.

PubMed

Orchard, Jacob; Price, Joseph

2017-05-01

Black mothers are 60 percent more likely than white mothers to have preterm births and twice as likely to have a baby with low birth weight. We examine whether these black-white gaps in birth outcomes are larger in counties with higher levels of racial prejudice. We use data from the restricted-use natality files in the United States, which provide information on birth weight, gestation, and maternal characteristics for over 31 million births from 2002 to 2012, combined with county-level data measures of both explicit and implicit racial prejudice from Project Implicit from over a million individuals who took the Implicit Association Test during this same period. We compare counties that are one standard deviation above the mean (high prejudice) with those that are one standard deviation below the mean (low prejudice) in terms of their average level of racial prejudice. The black-white gap in low birth weight is 14 percent larger in counties with high implicit racial prejudice compared to counties with low prejudice. The black-white gap in preterm births is 29 percent larger in the high prejudice counties. The gaps are even larger when we use explicit measures of racial prejudice with high prejudice counties having a black-white gap that is 22 percent larger for low birth weight and 36 percent larger for preterm births. These relationships do not appear to be biased by the way the prejudice sample is constructed, since the racial gap in birth outcomes is unrelated to other county-level biases such as those based on gender or sexual orientation. The black-white gap in United States' birth outcomes is larger in those counties that have the highest levels of racial prejudice. This is true for both implicit and explicit racial prejudice, though the strength of the relationship is strongest for explicit racial prejudice. Copyright © 2017 Elsevier Ltd. All rights reserved.

The predictive effect of empathy and social norms on adolescents' implicit and explicit stigma responses.

PubMed

Silke, Charlotte; Swords, Lorraine; Heary, Caroline

2017-11-01

Research indicates that adolescents who experience mental health difficulties are frequently stigmatised by their peers. Stigmatisation is associated with a host of negative social and psychological effects, which impacts a young person's well-being. As a result, the development of effective anti-stigma strategies is considered a major research priority. However, in order to design effective stigma reduction strategies, researchers must be informed by an understanding of the factors that influence the expression of stigma. Although evidence suggests that empathy and social norms have a considerable effect on adolescents' social attitudes and behaviours, research has yet to examine whether these factors significantly influence adolescents' responses toward their peers with mental health difficulties. Thus, this study aims to examine whether empathy (cognitive and affective) and peer norms (descriptive and injunctive) influence adolescents' implicit and explicit stigmatising responses toward peers with mental health problems. A total of 570 (221 male and 348 female; 1 non-specified) adolescents, aged between 13 and 18 years (M = 15.51, SD = 1.13), participated in this research. Adolescents read vignettes describing male/female depressed and 'typically developing' peers. Adolescents answered questions assessing their stigmatising responses toward each target, as well as their empathic responding and normative perceptions. A sub-sample of participants (n=173) also completed an IAT assessing their implicit stigmatising responses. Results showed that descriptive norms exerted a substantial effect on adolescents' explicit responses. Cognitive empathy, affective empathy and injunctive norms exerted more limited effects on explicit responses. No significant effects were observed for implicit stigma. Overall, empathy was found to have limited effects on adolescents' explicit and implicit stigmatising responses, which may suggest that other contextual variables moderate the effects of dispositional empathy on responding. In conclusion, these findings suggest that tackling the perception of negative descriptive norms may be an effective strategy for reducing explicit stigmatising responses among adolescents. Copyright © 2017 Elsevier B.V. All rights reserved.

Implicit-explicit (IMEX) Runge-Kutta methods for non-hydrostatic atmospheric models

NASA Astrophysics Data System (ADS)

Gardner, David J.; Guerra, Jorge E.; Hamon, François P.; Reynolds, Daniel R.; Ullrich, Paul A.; Woodward, Carol S.

2018-04-01

The efficient simulation of non-hydrostatic atmospheric dynamics requires time integration methods capable of overcoming the explicit stability constraints on time step size arising from acoustic waves. In this work, we investigate various implicit-explicit (IMEX) additive Runge-Kutta (ARK) methods for evolving acoustic waves implicitly to enable larger time step sizes in a global non-hydrostatic atmospheric model. The IMEX formulations considered include horizontally explicit - vertically implicit (HEVI) approaches as well as splittings that treat some horizontal dynamics implicitly. In each case, the impact of solving nonlinear systems in each implicit ARK stage in a linearly implicit fashion is also explored. The accuracy and efficiency of the IMEX splittings, ARK methods, and solver options are evaluated on a gravity wave and baroclinic wave test case. HEVI splittings that treat some vertical dynamics explicitly do not show a benefit in solution quality or run time over the most implicit HEVI formulation. While splittings that implicitly evolve some horizontal dynamics increase the maximum stable step size of a method, the gains are insufficient to overcome the additional cost of solving a globally coupled system. Solving implicit stage systems in a linearly implicit manner limits the solver cost but this is offset by a reduction in step size to achieve the desired accuracy for some methods. Overall, the third-order ARS343 and ARK324 methods performed the best, followed by the second-order ARS232 and ARK232 methods.

Defensive function of persecutory delusion and discrepancy between explicit and implicit self-esteem in schizophrenia: study using the Brief Implicit Association Test

PubMed Central

Nakamura, Mitsuo; Hayakawa, Tomomi; Okamura, Aiko; Kohigashi, Mutsumi; Fukui, Kenji; Narumoto, Jin

2015-01-01

Background If delusions serve as a defense mechanism in schizophrenia patients with paranoia, then they should show normal or high explicit self-esteem and low implicit self-esteem. However, the results of previous studies are inconsistent. One possible explanation for this inconsistency is that there are two types of paranoia, “bad me” (self-blaming) paranoia and “poor me” (non-self-blaming) paranoia. We thus examined implicit and explicit self-esteem and self-blaming tendency in patients with schizophrenia and schizoaffective disorder. We hypothesized that patients with paranoia would show lower implicit self-esteem and only those with non-self-blaming paranoia would experience a discrepancy between explicit and implicit self-esteem. Methods Participants consisted of patients with schizophrenia and schizoaffective disorder recruited from a day hospital (N=71). Participants were assessed for psychotic symptoms, using the Brief Psychiatric Rating Scale (BPRS), and self-blaming tendency, using the brief COPE. We also assessed explicit self-esteem, using the Rosenberg Self-Esteem Scale (RSES), implicit self-esteem, using Brief Implicit Association Test (BIAT), and discrepancy between explicit and implicit self-esteem. Results Contrary to our hypothesis, implicit self-esteem in paranoia and nonparanoia showed no statistical difference. As expected, only patients with non-self-blaming paranoia experienced a discrepancy between explicit and implicit self-esteem; other groups showed no such discrepancy. Conclusion These results suggest that persecutory delusion plays a defensive role in non-self-blaming paranoia. PMID:25565849

Coupling Protein Side-Chain and Backbone Flexibility Improves the Re-design of Protein-Ligand Specificity.

PubMed

Ollikainen, Noah; de Jong, René M; Kortemme, Tanja

2015-01-01

Interactions between small molecules and proteins play critical roles in regulating and facilitating diverse biological functions, yet our ability to accurately re-engineer the specificity of these interactions using computational approaches has been limited. One main difficulty, in addition to inaccuracies in energy functions, is the exquisite sensitivity of protein-ligand interactions to subtle conformational changes, coupled with the computational problem of sampling the large conformational search space of degrees of freedom of ligands, amino acid side chains, and the protein backbone. Here, we describe two benchmarks for evaluating the accuracy of computational approaches for re-engineering protein-ligand interactions: (i) prediction of enzyme specificity altering mutations and (ii) prediction of sequence tolerance in ligand binding sites. After finding that current state-of-the-art "fixed backbone" design methods perform poorly on these tests, we develop a new "coupled moves" design method in the program Rosetta that couples changes to protein sequence with alterations in both protein side-chain and protein backbone conformations, and allows for changes in ligand rigid-body and torsion degrees of freedom. We show significantly increased accuracy in both predicting ligand specificity altering mutations and binding site sequences. These methodological improvements should be useful for many applications of protein-ligand design. The approach also provides insights into the role of subtle conformational adjustments that enable functional changes not only in engineering applications but also in natural protein evolution.

Not explicit but implicit memory is influenced by individual perception style

PubMed Central

Tsushima, Yoshiaki

2018-01-01

Not only explicit but also implicit memory has considerable influence on our daily life. However, it is still unclear whether explicit and implicit memories are sensitive to individual differences. Here, we investigated how individual perception style (global or local) correlates with implicit and explicit memory. As a result, we found that not explicit but implicit memory was affected by the perception style: local perception style people more greatly used implicit memory than global perception style people. These results help us to make the new effective application adapting to individual perception style and understand some clinical symptoms such as autistic spectrum disorder. Furthermore, this finding might give us new insight of memory involving consciousness and unconsciousness as well as relationship between implicit/explicit memory and individual perception style. PMID:29370212

Not explicit but implicit memory is influenced by individual perception style.

PubMed

Hine, Kyoko; Tsushima, Yoshiaki

2018-01-01

Not only explicit but also implicit memory has considerable influence on our daily life. However, it is still unclear whether explicit and implicit memories are sensitive to individual differences. Here, we investigated how individual perception style (global or local) correlates with implicit and explicit memory. As a result, we found that not explicit but implicit memory was affected by the perception style: local perception style people more greatly used implicit memory than global perception style people. These results help us to make the new effective application adapting to individual perception style and understand some clinical symptoms such as autistic spectrum disorder. Furthermore, this finding might give us new insight of memory involving consciousness and unconsciousness as well as relationship between implicit/explicit memory and individual perception style.

[Effects of an implicit internal working model on attachment in information processing assessed using Go/No-Go Association Task].

PubMed

Fujii, Tsutomu; Uebuchi, Hisashi; Yamada, Kotono; Saito, Masahiro; Ito, Eriko; Tonegawa, Akiko; Uebuchi, Marie

2015-06-01

The purposes of the present study were (a) to use both a relational-anxiety Go/No-Go Association Task (GNAT) and an avoidance-of-intimacy GNAT in order to assess an implicit Internal Working Model (IWM) of attachment; (b) to verify the effects of both measured implicit relational anxiety and implicit avoidance of intimacy on information processing. The implicit IWM measured by GNAT differed from the explicit IWM measured by questionnaires in terms of the effects on information processing. In particular, in subliminal priming tasks involving with others, implicit avoidance of intimacy predicted accelerated response times with negative stimulus words about attachment. Moreover, after subliminally priming stimulus words about self, implicit relational anxiety predicted delayed response times with negative stimulus words about attachment.

Changes of explicitly and implicitly measured self-esteem in the treatment of major depression: evidence for implicit self-esteem compensation.

PubMed

Wegener, Ingo; Geiser, Franziska; Alfter, Susanne; Mierke, Jan; Imbierowicz, Katrin; Kleiman, Alexandra; Koch, Anne Sarah; Conrad, Rupert

2015-04-01

Self-esteem has been claimed to be an important factor in the development and maintenance of depression. Whereas explicit self-esteem is usually reduced in depressed individuals, studies on implicitly measured self-esteem in depression exhibit a more heterogeneous pattern of results, and the role of implicit self-esteem in depression is still ambiguous. Previous research on implicit self-esteem compensation (ISEC) revealed that implicit self-esteem can mirror processes of self-esteem compensation under conditions that threaten self-esteem. We assume that depressed individuals experience a permanent threat to their selves resulting in enduring processes of ISEC. We hypothesize that ISEC as measured by implicit self-esteem will decrease when individuals recover from depression. 45 patients with major depression received an integrative in-patient treatment in the Psychosomatic University Hospital Bonn, Germany. Depression was measured by the depression score of the Hospital Anxiety and Depression Scale (HADS-D). Self-esteem was assessed explicitly using the Rosenberg Self-Esteem Scale (RSES) and implicitly by the Implicit Association Test (IAT) and the Name Letter Test (NLT). As expected for a successful treatment of depression, depression scores declined during the eight weeks of treatment and explicit self-esteem rose. In line with our hypothesis, both measures of implicit self-esteem decreased, indicating reduced processes of ISEC. It still remains unclear, under which conditions there is an overlap of measures of implicit and explicit self-esteem. The results lend support to the concept of ISEC and demonstrate the relevance of implicit self-esteem and self-esteem compensation for the understanding of depression. Copyright © 2014 Elsevier Inc. All rights reserved.

Primary motor and premotor cortex in implicit sequence learning--evidence for competition between implicit and explicit human motor memory systems.

PubMed

Kantak, Shailesh S; Mummidisetty, Chaithanya K; Stinear, James W

2012-09-01

Implicit and explicit memory systems for motor skills compete with each other during and after motor practice. Primary motor cortex (M1) is known to be engaged during implicit motor learning, while dorsal premotor cortex (PMd) is critical for explicit learning. To elucidate the neural substrates underlying the interaction between implicit and explicit memory systems, adults underwent a randomized crossover experiment of anodal transcranial direct current stimulation (AtDCS) applied over M1, PMd or sham stimulation during implicit motor sequence (serial reaction time task, SRTT) practice. We hypothesized that M1-AtDCS during practice will enhance online performance and offline learning of the implicit motor sequence. In contrast, we also hypothesized that PMd-AtDCS will attenuate performance and retention of the implicit motor sequence. Implicit sequence performance was assessed at baseline, at the end of acquisition (EoA), and 24 h after practice (retention test, RET). M1-AtDCS during practice significantly improved practice performance and supported offline stabilization compared with Sham tDCS. Performance change from EoA to RET revealed that PMd-AtDCS during practice attenuated offline stabilization compared with M1-AtDCS and sham stimulation. The results support the role of M1 in implementing online performance gains and offline stabilization for implicit motor sequence learning. In contrast, enhancing the activity within explicit motor memory network nodes such as the PMd during practice may be detrimental to offline stabilization of the learned implicit motor sequence. These results support the notion of competition between implicit and explicit motor memory systems and identify underlying neural substrates that are engaged in this competition. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Finding molecular dioxygen tunnels in homoprotocatechuate 2,3-dioxygenase: implications for different reactivity of identical subunits.

PubMed

Xu, Liang; Zhao, Weijie; Wang, Xicheng

2010-01-01

Extradiol dioxygenases facilitate microbial aerobic degradation of catechol and its derivatives by activating molecular dioxygen and incorporating both oxygen atoms into their substrates. Experimental and theoretical studies have focused on the mechanism of the reaction at the active site. However, whether the catalytic rate is limited by O(2) access to the active site has not yet been explored. Here, we choose a recently solved X-ray structure of homoprotocatechuate 2,3-dioxygenase as a typical example to determine potential pathways for O(2) migration from the solvent into the enzyme center. On the basis of the trajectories of two 10-ns molecular dynamics simulations, implicit ligand sampling was used to calculate the 3D free energy map for O(2) inside the protein. The energetically optimal routes for O(2) diffusion were identified for each subunit of the homotetrameric protein structure. The O(2) tunnels formed because of thermal fluctuations were also characterized by connecting elongated cavities inside the protein. By superimposing the favorable O(2) tunnels on to the free energy map, both energetically and geometrically preferred O(2) pathways were determined, as also were the amino acids that may be critical for O(2) passage along these paths. Our results demonstrate that identical subunits possess quite distinct O(2) tunnels. The order of O(2) affinity of these tunnels is generally consistent with the order of the catalytic rate of each subunit. As a consequence, the probability of finding the reaction product is highest in the subunit containing the highest O(2) affinity pathway.

Toward the accurate first-principles prediction of ionization equilibria in proteins.

PubMed

Khandogin, Jana; Brooks, Charles L

2006-08-08

The calculation of pK(a) values for ionizable sites in proteins has been traditionally based on numerical solutions of the Poisson-Boltzmann equation carried out using a high-resolution protein structure. In this paper, we present a method based on continuous constant pH molecular dynamics (CPHMD) simulations, which allows the first-principles description of protein ionization equilibria. Our method utilizes an improved generalized Born implicit solvent model with an approximate Debye-Hückel screening function to account for salt effects and the replica-exchange (REX) protocol for enhanced conformational and protonation state sampling. The accuracy and robustness of the present method are demonstrated by 1 ns REX-CPHMD titration simulations of 10 proteins, which exhibit anomalously large pK(a) shifts for the carboxylate and histidine side chains. The experimental pK(a) values of these proteins are reliably reproduced with a root-mean-square error ranging from 0.6 unit for proteins containing few buried ionizable side chains to 1.0 unit or slightly higher for proteins containing ionizable side chains deeply buried in the core and experiencing strong charge-charge interactions. This unprecedented level of agreement with experimental benchmarks for the de novo calculation of pK(a) values suggests that the CPHMD method is maturing into a practical tool for the quantitative prediction of protein ionization equilibria, and this, in turn, opens a door to atomistic simulations of a wide variety of pH-coupled conformational phenomena in biological macromolecules such as protein folding or misfolding, aggregation, ligand binding, membrane interaction, and catalysis.

Simultaneous optimization of biomolecular energy function on features from small molecules and macromolecules

PubMed Central

Park, Hahnbeom; Bradley, Philip; Greisen, Per; Liu, Yuan; Mulligan, Vikram Khipple; Kim, David E.; Baker, David; DiMaio, Frank

2017-01-01

Most biomolecular modeling energy functions for structure prediction, sequence design, and molecular docking, have been parameterized using existing macromolecular structural data; this contrasts molecular mechanics force fields which are largely optimized using small-molecule data. In this study, we describe an integrated method that enables optimization of a biomolecular modeling energy function simultaneously against small-molecule thermodynamic data and high-resolution macromolecular structural data. We use this approach to develop a next-generation Rosetta energy function that utilizes a new anisotropic implicit solvation model, and an improved electrostatics and Lennard-Jones model, illustrating how energy functions can be considerably improved in their ability to describe large-scale energy landscapes by incorporating both small-molecule and macromolecule data. The energy function improves performance in a wide range of protein structure prediction challenges, including monomeric structure prediction, protein-protein and protein-ligand docking, protein sequence design, and prediction of the free energy changes by mutation, while reasonably recapitulating small-molecule thermodynamic properties. PMID:27766851

Implicit Learning as an Ability

ERIC Educational Resources Information Center

Kaufman, Scott Barry; DeYoung, Caroline G.; Gray, Jeremy R.; Jimenez, Luis; Brown, Jamie; Mackintosh, Nicholas

2010-01-01

The ability to automatically and implicitly detect complex and noisy regularities in the environment is a fundamental aspect of human cognition. Despite considerable interest in implicit processes, few researchers have conceptualized implicit learning as an ability with meaningful individual differences. Instead, various researchers (e.g., Reber,…

Implicit attitudes, emotions, and helping intentions of mental health workers toward their clients.

PubMed

Brener, Loren; Rose, Grenville; von Hippel, Courtney; Wilson, Hannah

2013-06-01

The attitudes of mental health care workers toward their clients may influence the quality of care they provide. There is growing recognition of the role of implicit attitudes in behavior toward people with stigmatized illnesses, such as mental illness, and of the need to measure these separately from explicit attitudes. Seventy-four mental health workers completed implicit and explicit measure of attitudes toward people with mental illness. The participants were also asked about their intention to help people with mental illness and their emotional reactions toward people with a mental illness. The findings show that the implicit attitudes of the health workers toward clients with a mental illness are somewhat negative despite the fact that their explicit attitudes are somewhat positive. Although both implicit and explicit attitudes predicted negative emotions, only implicit attitudes were related to helping intentions. This study highlights the association between implicit attitudes and behavioral intentions and confirms the importance of addressing implicit attitudes in mental health research.

Cultural variation in implicit independence: An extension of Kitayama et al. ().

PubMed

Park, Jiyoung; Uchida, Yukiko; Kitayama, Shinobu

2016-08-01

Previous research shows that European Americans are consistently more independent (or less interdependent) than Japanese when implicit indices are used to assess independence (vs. interdependence). The present work extended this evidence by including a novel implicit association test (IAT), as an index of implicit attitude towards independence and interdependence. Consistent with the previous findings, as compared to Japanese, Americans were significantly higher in multiple indices of implicit independence (vs. interdependence) including personal (vs. social) self-definition, experience of disengaging (vs. engaging) emotions and personal (vs. social) form of happiness. Furthermore, as compared to Japanese, Americans had a significantly more positive implicit attitude towards independence assessed with the IAT. As also observed in the previous research, explicit measures showed inconsistent cross-cultural patterns. Lastly, we observed little statistical within-culture coherence among the implicit measures of independence (vs. interdependence), consistent with a view that the implicit indices capture alternative ways for individuals to achieve the cultural mandate of independence or interdependence. © 2015 International Union of Psychological Science.

Implicit motives, explicit traits, and task and contextual performance at work.

PubMed

Lang, Jonas W B; Zettler, Ingo; Ewen, Christian; Hülsheger, Ute R

2012-11-01

Personality psychologists have long argued that explicit traits (as measured by questionnaires) channel the expression of implicit motives (as measured by coding imaginative verbal behavior) such that both interact in the prediction of relevant life outcome variables. In the present research, we apply these ideas in the context of industrial and organizational psychology and propose that 2 explicit traits work as channels for the expression of 3 core implicit motives in task and contextual job performance (extraversion for implicit affiliation and implicit power; explicit achievement for implicit achievement). As a test of these theoretical ideas, we report a study in which employees (N = 241) filled out a questionnaire booklet and worked on an improved modern implicit motive measure, the operant motive test. Their supervisors rated their task and contextual performance. Results support 4 of the 6 theoretical predictions and show that interactions between implicit motives and explicit traits increase the explained criterion variance in both task and contextual performance. (c) 2012 APA, all rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Andersson, Gunther G., E-mail: gunther.andersson@flinders.edu.au, E-mail: vladimir.golovko@canterbury.ac.nz, E-mail: greg.metha@adelaide.edu.au; Al Qahtani, Hassan S.; Golovko, Vladimir B., E-mail: gunther.andersson@flinders.edu.au, E-mail: vladimir.golovko@canterbury.ac.nz, E-mail: greg.metha@adelaide.edu.au

Chemically made, atomically precise phosphine-stabilized clusters Au{sub 9}(PPh{sub 3}){sub 8}(NO{sub 3}){sub 3} were deposited on titania and silica from solutions at various concentrations and the samples heated under vacuum to remove the ligands. Metastable induced electron spectroscopy was used to determine the density of states at the surface, and X-ray photoelectron spectroscopy for analysing the composition of the surface. It was found for the Au{sub 9} cluster deposited on titania that the ligands react with the titania substrate. Based on analysis using the singular value decomposition algorithm, the series of MIE spectra can be described as a linear combination ofmore » 3 base spectra that are assigned to the spectra of the substrate, the phosphine ligands on the substrate, and the Au clusters anchored to titania after removal of the ligands. On silica, the Au clusters show significant agglomeration after heat treatment and no interaction of the ligands with the substrate can be identified.« less

Typical aqueous rare earth element behavior in co-produced Brines, Wyoming

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nye, Charles; Quillinan, Scott; McLing, Travis

Normalization of Rare Earth Elements (REEs) is important to remove the distracting effects of the Oddo–Harkins rule and provide a meaningful baseline. Normalizations for rocks are well developed and include chondritic meteorites, UCC, PM, PAAS, and NASC. However normalizations for aqueous REEs are limited to oceanic regions such as the North Pacific Deep Water or North Atlantic Surface Water. This leaves water in contact with continental lithologies without a suitable normalization. We present a preliminary continental aqueous REE normalization derived from 38 deep basin hydrocarbon brines in Wyoming. The REEs in these waters are seven orders of magnitude more dilutemore » than NASC but with significant europium enrichment. Gromet 1984 reports NASC Eu/Eu* is 0.2179, whereas in the normalization offered here, Eu/Eu* is 3.868. These waters also are free from the distracting reduction-oxidation cerium behavior found in ocean normalizations. Because these samples exhibit both the uniform behavior of NASC and the absolute concentration of seawater, a normalization based upon them offers a unique combination of the advantages of both. We used single-peak gaussian analysis to quantify the mean values for each REE and estimate the distribution variability. Additional sample collection during the last year revealed that the Powder River Basin (PRB) is atypical relative to the other sampled basins of Wyoming. Those other basins are the Wind River Basin (WRB) Green River Basin (GRB) and Wamsutter Area (WA). A pre-normalization gadolinium anomaly (Gd/Gd*) of between 4 and 23 with a mean of 11.5, defines the PRB samples. Other basins in this study range from 1 to 7 with a mean of 2.8. Finally, we present a preliminary model for ligand-based behavior of REEs in these samples. This model identifies bicarbonate, bromide, and chloride as forming significant complexes with REEs contributing to REE solubility. The ligand model explains observed REEs in the sampled Cretaceous and Paleocene clastic reservoirs. However, the presence of more REEs than predicted in six samples suggests that there is an additional, unconsidered ligand contributing to REE dissolution. Further work will identify this ligand, which appears to be confined to calcium-cemented and dolostone systems.« less

Metal isotope coded profiling of organic ligands by mass spectrometry in aquatic environments

NASA Astrophysics Data System (ADS)

Wichard, Thomas; Deicke, Michael; Frieder Mohr, Jan; Klein, Martin

2017-04-01

Metal isotope coded profiling (MICP) introduces a universal discovery platform for metal chelating natural products that act as metallophores, ion buffers or sequestering agents. The detection of cation and oxoanion complexing ligands is facilitated by the identification of unique isotopic signatures created by the application of isotopically pure metals. We present a targeted analysis of low-molecular-weight organic ligands based on fast UHPLC-ESI-MS measurements. Replacement of, for example, natural iron or molybdenum with isotopically pure 54Fe/58Fe (ratio 1:1) or 95Mo/98Mo (ratio 1:1) causes easily detectable unique isotopic signatures in the mass spectra of potential metal-complexing ligands. This can be achieved under laboratory conditions not only in growth media, but also by spiking directly aqueous samples or solid-phase extracts. Importantly, as the relative affinity of the metallophores for e.g., Mo or Fe is dependent on the pH, all experiments needs to be conducted under pH-controlled conditions. The improved ionization efficiency of some metal complexes helps to enhance the signal-to-noise ratio compared to the free ligand at the same chromatographic conditions. The methodology does not necessarily depend on HR-ESI-MS measurements (e.g., Q-Exactive Orbitrap) and can be applied to any mass spectrometer. With MICP, two birds can be killed with one stone: (i) the identification of metallophores (e.g., siderophores, molybdophores) for metal uptake by any organism and (ii) organic ligands which solely work as metal buffer in dissolved organic matter (DOM). We currently address following two main research lines: First, DOM has often been used as a proxy for bio-productivity in terms of a carbon source; however, the specific impact of DOM as a "metal buffer" for biological processes is still under-investigated. Upon the administration of individual isotopes or isotopic pairs, for example, 54Fe/58Fe, 63Cu/65Cu, 66Zn/68Zn, or 95Mo/98Mo and subsequent measurements by mass spectrometry, organic ligands can be identified that contribute potentially to the regulation of bioavailability and toxicity of metals in the water column. Secondly, metal acquisition by ligand exchange processes is vital for macroalgae-bacteria interactions. Both alga and bacteria contribute to the "soup of organic ligands" which potentially increases the bioavailability of metals due to various ligand exchanges with DOM. In particular, we will outline the analytical process resulting in the identification of ligands in the chemosphere of the marine macroalga Ulva (Chlorophyta) and its associated bacteria. In summary, the identification of metal organic ligands in natural samples will pave the way for understanding the organic ligand-mediated metal acquisition shuttled from DOM to alga. (References: Wichard T. (2016) Front. Mar. Sci. 3:131; Deicke M., Mohr J.M., Wichard T. (2014) Analyst, 139, 6096-6099)

Implicit and explicit attitudes towards conventional and complementary and alternative medicine treatments: Introduction of an Implicit Association Test.

PubMed

Green, James A; Hohmann, Cynthia; Lister, Kelsi; Albertyn, Riani; Bradshaw, Renee; Johnson, Christine

2016-06-01

This study examined associations between anticipated future health behaviour and participants' attitudes. Three Implicit Association Tests were developed to assess safety, efficacy and overall attitude. They were used to examine preference associations between conventional versus complementary and alternative medicine among 186 participants. A structural equation model suggested only a single implicit association, rather than three separate domains. However, this single implicit association predicted additional variance in anticipated future use of complementary and alternative medicine beyond explicit. Implicit measures should give further insight into motivation for complementary and alternative medicine use. © The Author(s) 2014.

Implicit cognitive processes in psychopathology: an introduction.

PubMed

Wiers, Reinout W; Teachman, Bethany A; De Houwer, Jan

2007-06-01

Implicit or automatic processes are important in understanding the etiology and maintenance of psychopathological problems. In order to study implicit processes in psychopathology, measures are needed that are valid and reliable when applied to clinical problems. One of the main topics in this special issue concerns the development and validation of new or modified implicit tests in different domains of psychopathology. The other main topic concerns the prediction of clinical outcomes and new ways to directly influence implicit processes in psychopathology. We summarize the contributions to this special issue and discuss how they further our knowledge of implicit processes in psychopathology and how to measure them.

Examining the Presence, Consequences, and Reduction of Implicit Bias in Health Care: A Narrative Review

PubMed Central

Zestcott, Colin A.; Blair, Irene V.; Stone, Jeff

2016-01-01

Recent evidence suggests that one possible cause of disparities in health outcomes for stigmatized groups is the implicit biases held by health care providers. In response, several health care organizations have called for, and developed, new training in implicit bias for their providers. This review examines current evidence on the role that provider implicit bias may play in health disparities, and whether training in implicit bias can effectively reduce the biases that providers exhibit. Directions for future research on the presence and consequences of provider implicit bias, and best practices for training to reduce such bias, will be discussed. PMID:27547105

Implicit and explicit preferences for physical attractiveness in a romantic partner: a double dissociation in predictive validity.

PubMed

Eastwick, Paul W; Eagly, Alice H; Finkel, Eli J; Johnson, Sarah E

2011-11-01

Five studies develop and examine the predictive validity of an implicit measure of the preference for physical attractiveness in a romantic partner. Three hypotheses were generally supported. First, 2 variants of the go/no-go association task revealed that participants, on average, demonstrate an implicit preference (i.e., a positive spontaneous affective reaction) for physical attractiveness in a romantic partner. Second, these implicit measures were not redundant with a traditional explicit measure: The correlation between these constructs was .00 on average, and the implicit measures revealed no reliable sex differences, unlike the explicit measure. Third, explicit and implicit measures exhibited a double dissociation in predictive validity. Specifically, explicit preferences predicted the extent to which attractiveness was associated with participants' romantic interest in opposite-sex photographs but not their romantic interest in real-life opposite-sex speed-daters or confederates. Implicit preferences showed the opposite pattern. This research extends prior work on implicit processes in romantic relationships and offers the first demonstration that any measure of a preference for a particular characteristic in a romantic partner (an implicit measure of physical attractiveness, in this case) predicts individuals' evaluation of live potential romantic partners.

Unfinished nursing care, missed care, and implicitly rationed care: State of the science review.

PubMed

Jones, Terry L; Hamilton, Patti; Murry, Nicole

2015-06-01

The purposes of this review of unfinished care were to: (1) compare conceptual definitions and frameworks associated with unfinished care and related synonyms (i.e. missed care, implicitly rationed care; and care left undone); (2) compare and contrast approaches to instrumentation; (3) describe prevalence and patterns; (4) identify antecedents and outcomes; and (5) describe mitigating interventions. A literature search in CINAHL and MEDLINE identified 1828 articles; 54 met inclusion criteria. Search terms included: implicit ration*, miss* care, ration* care, task* undone, and unfinish*care. Analysis was performed in three phases: initial screening and sorting, comprehensive review for data extraction (first author), and confirmatory review to validate groupings, major themes, and interpretations (second author). Reviewed literature included 42 quantitative reports; 7 qualitative reports; 1 mixed method report; and 4 scientific reviews. With one exception, quantitative studies involved observational cross-sectional survey designs. A total of 22 primary samples were identified; 5 involved systematic sampling. The response rate was >60% in over half of the samples. Unfinished care was measured with 14 self-report instruments. Most nursing personnel (55-98%) reported leaving at least 1 task undone. Estimates increased with survey length, recall period, scope of response referent, and scope of resource scarcity considered. Patterns of unfinished care were consistent with the subordination of teaching and emotional support activities to those related to physiologic needs and organizational audits. Predictors of unfinished care included perceived team interactions, adequacy of resources, safety climate, and nurse staffing. Unfinished care is a predictor of: decreased nurse-reported care quality, decreased patient satisfaction; increased adverse events; increased turnover; decreased job and occupational satisfaction; and increased intent to leave. Unfinished care is a significant problem in acute care hospitals internationally. Prioritization strategies of nurses leave patients vulnerable to unmet educational, emotional, and psychological needs. Key limitations of the science include the threat of common method/source bias, a lack of transparency regarding the use of combined samples and secondary analysis, inconsistency in the reporting format for unfinished care prevalence, and a paucity of intervention studies. Copyright © 2015 Elsevier Ltd. All rights reserved.

Implicit Statistical Learning and Language Skills in Bilingual Children

ERIC Educational Resources Information Center

Yim, Dongsun; Rudoy, John

2013-01-01

Purpose: Implicit statistical learning in 2 nonlinguistic domains (visual and auditory) was used to investigate (a) whether linguistic experience influences the underlying learning mechanism and (b) whether there are modality constraints in predicting implicit statistical learning with age and language skills. Method: Implicit statistical learning…

Structured implicit review: a new method for monitoring nursing care quality.

PubMed

Pearson, M L; Lee, J L; Chang, B L; Elliott, M; Kahn, K L; Rubenstein, L V

2000-11-01

Nurses' independent decisions about assessment, treatment, and nursing interventions for hospitalized patients are important determinants of quality of care. Physician peer implicit review of medical records has been central to Medicare quality management and is considered the gold standard for reviewing physician care, but peer implicit review of nursing processes of care has not received similar attention. The objective of this study was to develop and evaluate nurse structured implicit review (SIR) methods. We developed SIR instruments for rating the quality of inpatient nursing care for congestive heart failure (CHF) and cerebrovascular accident (CVA). Nurse reviewers used the SIR form to rate a nationally representative sample of randomly selected medical records for each disease from 297 acute care hospitals in 5 states (collected by the RAND-HCFA Prospective Payment System study). The study subjects were elderly Medicare inpatients with CHF (n = 291) or CVA (n = 283). We developed and tested scales reflecting domains of nursing process, evaluated interrater and interitem reliability, and assessed the extent to which items and scales predicted overall ratings of the quality of nursing care. Interrater reliability for 14 of 16 scales (CHF) or 10 of 16 scales (CVA) was > or = 0.40. Interitem reliability was > 0.80 for all but 1 scale (both diseases). Functional Assessment, Physical Assessment, and Medication Tracking ratings were the strongest predictors of overall nursing quality ratings (P < 0.001 for each). Nurse peer review with SIR has adequate interrater and excellent scale reliabilities and can be a valuable tool for assessing nurse performance.

Discrimination, Racial Bias, and Telomere Length in African-American Men

PubMed Central

Chae, David H.; Nuru-Jeter, Amani M.; Adler, Nancy E.; Brody, Gene H.; Lin, Jue; Blackburn, Elizabeth H.; Epel, Elissa S.

2013-01-01

Background Leukocyte telomere length (LTL) is an indicator of general systemic aging, with shorter LTL being associated with several chronic diseases of aging and earlier mortality. Identifying factors related to LTL among African Americans may yield insights into mechanisms underlying racial disparities in health. Purpose To test whether the combination of more frequent reports of racial discrimination and holding a greater implicit anti-black racial bias is associated with shorter LTL among African-American men. Methods Cross-sectional study of a community sample of 92 African-American men aged between 30 and 50 years. Participants were recruited from February to May 2010. Ordinary least squares regressions were used to examine LTL in kilobase pairs in relation to racial discrimination and implicit racial bias. Data analysis was completed in July 2013. Results After controlling for chronologic age, socioeconomic, and health-related characteristics, the interaction between racial discrimination and implicit racial bias was significantly associated with LTL (b= −0.10, SE=0.04, p=0.02). Those demonstrating a stronger implicit anti-black bias and reporting higher levels of racial discrimination had the shortest LTL. Household income-to-poverty threshold ratio was also associated with LTL (b=0.05, SE=0.02, p<0.01). Conclusions Results suggest that multiple levels of racism, including interpersonal experiences of racial discrimination and the internalization of negative racial bias, operate jointly to accelerate biological aging among African-American men. Societal efforts to address racial discrimination in concert with efforts to promote positive in-group racial attitudes may protect against premature biological aging in this population. PMID:24439343

Explicit and Implicit Components of the Emotional Processing in Non-organic Vision Loss: Behavioral Evidence About the Role of Fear in Functional Blindness

PubMed Central

Scarpina, Federica; Melzi, Lisa; Castelnuovo, Gianluca; Mauro, Alessandro; Marzoli, Stefania B.; Molinari, Enrico

2018-01-01

Non-organic vision loss (NOVL), a functional partial or global vision loss, might be considered a manifestation of conversion disorder. The few previous studies focused on investigating the relationship between cerebral activity and subjective symptoms in NOVL; however, the emotional processing is still neglected. In the present case-controls study, we investigated the capability of two individuals diagnosed with NOVL to recognize implicitly the emotions of fear and anger; this was assessed through a facial emotion recognition task based on the redundant target effect. In addition, the level of alexithymia was measured by asking them to judge explicitly their ability to identify and describe emotions. Both individuals showed selective difficulties in recognizing the emotion of fear when their performance was contrasted with a matched control sample; they also mislabeled other emotional stimuli, judging them as fearful, when they were not. However, they did not report alexithymia when measured using a standard questionnaire. This preliminary investigation reports a mismatch between the implicit (i.e., the behavior in the experimental paradigm) and the explicit (i.e., the subjective evaluation of one’s own emotional capability) components of the emotional processing in NOVL. Moreover, fear seems to represent a critical emotion in this condition, as has been reported in other psychiatric disorders. However, possible difficulties in the emotional processing of fear would emerge only when they are inferred from an implicit behavior, instead of a subjective evaluation of one’s own emotional processing capability. PMID:29692751

Implicit affectivity in patients with borderline personality disorder.

PubMed

Dukalski, Bibiana; Quirin, Markus; Kersting, Anette; Suslow, Thomas; Donges, Uta-Susan

2017-01-01

It has been argued that borderline personality disorder (BPD) is related to an enhanced affective reactivity. According to findings from research based on self-report, individuals with BPD develop and feel more negative and less positive affect than healthy individuals. Implicit affectivity, which can be measured using indirect assessment methods, relates to processes of the impulsive, intuitive system. In the present study, implicit and explicit affectivity was examined in patients suffering from BPD compared to healthy persons. Thirty-five women with BPD and 35 healthy women participated in the study. Implicit affectivity was assessed using the Implicit Positive and Negative Affect Test (IPANAT). Measures of explicit state and trait affectivity were also administered. BPD women had lower explicit positive state and trait affect scores and higher negative state and trait affect scores than healthy women. They had also lower implicit positive affect but they did not differ from healthy women regarding implicit negative affect. Total number of comorbid disorders was correlated with both implicit positive and implicit negative affect. According to our data, BPD patients exhibit reduced implicit positive affect as well as reduced explicit positive affect compared to healthy persons. According to our IPANAT data, BPD patients are characterized by a normal disposition to develop negative affective reactions which is in line with a number of findings from psycho-physiological research on BPD. Self-reports of negative affectivity in BPD could be biased by negative distortion.

Context Effects of Alcohol Availability at Home: Implicit Alcohol Associations and the Prediction of Adolescents' Drinking Behavior.

PubMed

Peeters, Margot; Koning, Ina; Monshouwer, Karin; Vollebergh, Wilma A M; Wiers, Reinout W

2016-09-01

Recent studies suggest that the predictive effect of implicit alcohol associations is context dependent. Findings indicate that implicit associations are more easily retrieved in an alcohol-associated setting or context (e.g., bar) compared with a neutral setting. In line with this reasoning, we hypothesized that alcohol availability at home might moderate the relationship between implicit alcohol associations and future drinking behavior of adolescents. Participants were 262 at-risk adolescents (235 boys, 27 girls, adolescents with externalizing behavioral problems) with a mean age of 14.11 years (SD = 0.86, age range: 12-16 years) at baseline. Adolescents completed a questionnaire and a modified version of the Implicit Association Test (i.e., Single Category Implicit Association Test; SC-IAT). Stronger implicit alcohol associations predicted increase in frequency of alcohol use, only in adolescents who indicated that alcohol was available at home. No moderating effects were found for increase in quantity of alcohol use and problematic alcohol use, suggesting that implicit alcohol associations particularly influence the decision of whether to drink in adolescence. The findings illustrate that the availability of alcohol in the home setting influences adolescents' implicit alcohol associations and consequently affects the frequency of alcohol use. In this way, alcohol availability at home may be an important contextual factor to consider when examining the effect of implicit alcohol associations on the future drinking behavior of adolescents.

Using implicit attitudes of exercise importance to predict explicit exercise dependence symptoms and exercise behaviors.

PubMed

Forrest, Lauren N; Smith, April R; Fussner, Lauren M; Dodd, Dorian R; Clerkin, Elise M

2016-01-01

"Fast" (i.e., implicit) processing is relatively automatic; "slow" (i.e., explicit) processing is relatively controlled and can override automatic processing. These different processing types often produce different responses that uniquely predict behaviors. In the present study, we tested if explicit, self-reported symptoms of exercise dependence and an implicit association of exercise as important predicted exercise behaviors and change in problematic exercise attitudes. We assessed implicit attitudes of exercise importance and self-reported symptoms of exercise dependence at Time 1. Participants reported daily exercise behaviors for approximately one month, and then completed a Time 2 assessment of self-reported exercise dependence symptoms. Undergraduate males and females (Time 1, N = 93; Time 2, N = 74) tracked daily exercise behaviors for one month and completed an Implicit Association Test assessing implicit exercise importance and subscales of the Exercise Dependence Questionnaire (EDQ) assessing exercise dependence symptoms. Implicit attitudes of exercise importance and Time 1 EDQ scores predicted Time 2 EDQ scores. Further, implicit exercise importance and Time 1 EDQ scores predicted daily exercise intensity while Time 1 EDQ scores predicted the amount of days exercised. Implicit and explicit processing appear to uniquely predict exercise behaviors and attitudes. Given that different implicit and explicit processes may drive certain exercise factors (e.g., intensity and frequency, respectively), these behaviors may contribute to different aspects of exercise dependence.

Dissociation between implicit and explicit expectancies of cannabis use in adolescence.

PubMed

Schmits, Emilie; Maurage, Pierre; Thirion, Romain; Quertemont, Etienne

2015-12-30

Cannabis is one of the most commonly drugs used by teenagers. Expectancies about its effects play a crucial role in cannabis consumption. Various tools have been used to assess expectancies, mainly self-report questionnaires measuring explicit expectancies, but implicit measures based on experimental tasks have also been developed, measuring implicit expectancies. The aim of this study was to simultaneously assess implicit/explicit expectancies related to cannabis among adolescent users and non-users. 130 teenagers attending school (55 girls) were enrolled (Age: M=16.40 years); 43.84% had never used cannabis ("non-users") and 56.16% had used cannabis ("users"). They completed self-report questionnaires evaluating cannabis use, cannabis-related problems, effect expectancies (explicit expectancies), alcohol use, social and trait anxiety, depression, as well as three Implicit Association Tests (IAT) assessing implicit expectancies. Adolescents manifested more implicit affective associations (relaxation, excitation, negative) than neutral ones regarding cannabis. These were not related to explicit expectancies. Cannabis users reported more implicit relaxation expectancies and less negative explicit expectancies than non-users. The frequency of use and related problems were positively associated with the explicit expectancies regarding relaxation and enhancement, and were negatively associated with negative explicit expectancies and negative implicit expectancies. Findings indicate that implicit and explicit expectancies play different roles in cannabis use by adolescents. The implications for experimentation and prevention are discussed. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Using implicit attitudes of exercise importance to predict explicit exercise dependence symptoms and exercise behaviors

PubMed Central

Forrest, Lauren N.; Smith, April R.; Fussner, Lauren M.; Dodd, Dorian R.; Clerkin, Elise M.

2015-01-01

Objectives ”Fast” (i.e., implicit) processing is relatively automatic; “slow” (i.e., explicit) processing is relatively controlled and can override automatic processing. These different processing types often produce different responses that uniquely predict behaviors. In the present study, we tested if explicit, self-reported symptoms of exercise dependence and an implicit association of exercise as important predicted exercise behaviors and change in problematic exercise attitudes. Design We assessed implicit attitudes of exercise importance and self-reported symptoms of exercise dependence at Time 1. Participants reported daily exercise behaviors for approximately one month, and then completed a Time 2 assessment of self-reported exercise dependence symptoms. Method Undergraduate males and females (Time 1, N = 93; Time 2, N = 74) tracked daily exercise behaviors for one month and completed an Implicit Association Test assessing implicit exercise importance and subscales of the Exercise Dependence Questionnaire (EDQ) assessing exercise dependence symptoms. Results Implicit attitudes of exercise importance and Time 1 EDQ scores predicted Time 2 EDQ scores. Further, implicit exercise importance and Time 1 EDQ scores predicted daily exercise intensity while Time 1 EDQ scores predicted the amount of days exercised. Conclusion Implicit and explicit processing appear to uniquely predict exercise behaviors and attitudes. Given that different implicit and explicit processes may drive certain exercise factors (e.g., intensity and frequency, respectively), these behaviors may contribute to different aspects of exercise dependence. PMID:26195916

Racial Categorization Predicts Implicit Racial Bias in Preschool Children.

PubMed

Setoh, Peipei; Lee, Kristy J J; Zhang, Lijun; Qian, Miao K; Quinn, Paul C; Heyman, Gail D; Lee, Kang

2017-06-12

This research investigated the relation between racial categorization and implicit racial bias in majority and minority children. Chinese and Indian 3- to 7-year-olds from Singapore (N = 158) categorized Chinese and Indian faces by race and had their implicit and explicit racial biases measured. Majority Chinese children, but not minority Indian children, showed implicit bias favoring own race. Regardless of ethnicity, children's racial categorization performance correlated positively with implicit racial bias. Also, Chinese children, but not Indian children, displayed explicit bias favoring own race. Furthermore, children's explicit bias was unrelated to racial categorization performance and implicit bias. The findings support a perceptual-social linkage in the emergence of implicit racial bias and have implications for designing programs to promote interracial harmony. © 2017 The Authors. Child Development © 2017 Society for Research in Child Development, Inc.

Implicit Bias and Mental Health Professionals: Priorities and Directions for Research.

PubMed

Merino, Yesenia; Adams, Leslie; Hall, William J

2018-06-01

This Open Forum explores the role of implicit bias along the mental health care continuum, which may contribute to mental health disparities among vulnerable populations. Emerging research shows that implicit bias is prevalent among service providers. These negative or stigmatizing attitudes toward population groups are held at a subconscious level and are automatically activated during practitioner-client encounters. The authors provide examples of how implicit bias may impede access to care, clinical screening and diagnosis, treatment processes, and crisis response. They also discuss how implicit attitudes may manifest at the intersection between mental health and criminal justice institutions. Finally, they discuss the need for more research on the impact of implicit bias on health practices throughout the mental health system, including the development of interventions to address implicit bias among mental health professionals.

Cooperative Allosteric Ligand Binding in Calmodulin

NASA Astrophysics Data System (ADS)

Nandigrami, Prithviraj

Conformational dynamics is often essential for a protein's function. For example, proteins are able to communicate the effect of binding at one site to a distal region of the molecule through changes in its conformational dynamics. This so called allosteric coupling fine tunes the sensitivity of ligand binding to changes in concentration. A conformational change between a "closed" (apo) and an "open" (holo) conformation upon ligation often produces this coupling between binding sites. Enhanced sensitivity between the unbound and bound ensembles leads to a sharper binding curve. There are two basic conceptual frameworks that guide our visualization about ligand binding mechanisms. First, a ligand can stabilize the unstable "open" state from a dynamic ensemble of conformations within the unbound basin. This binding mechanism is called conformational selection. Second, a ligand can weakly bind to the low-affinity "closed" state followed by a conformational transition to the "open" state. In this dissertation, I focus on molecular dynamics simulations to understand microscopic origins of ligand binding cooperativity. A minimal model of allosteric binding transitions must include ligand binding/unbinding events, while capturing the transition mechanism between two distinct meta-stable free energy basins. Due in part to computational timescales limitations, work in this dissertation describes large-scale conformational transitions through a simplified, coarse-grained model based on the energy basins defined by the open and closed conformations of the protein Calmodulin (CaM). CaM is a ubiquitous calcium-binding protein consisting of two structurally similar globular domains connected by a flexible linker. The two domains of CaM, N-terminal domain (nCaM) and C-terminal domain (cCaM) consists of two helix-loop-helix motifs (the EF-hands) connected by a flexible linker. Each domain of CaM consists of two binding loops and binds 2 calcium ions each. The intact domain binds up to 4 calcium ions. The simulations use a coupled molecular dynamics/monte carlo scheme where the protein dynamics is simulated explicitly, while ligand binding/unbinding are treated implicitly. In the model, ligand binding/unbinding events coupled with a conformational change of the protein within the grand canonical ensemble. Here, ligand concentration is controlled through the chemical potential (micro). This allows us to use a simple thermodynamic model to analyze the simulated data and quantify binding cooperativity. Simulated binding titration curves are calculated through equilibrium simulations at different values of micro. First, I study domain opening transitions of isolated nCaM and cCaM in the absence of calcium. This work is motivated by results from a recent analytic variational model that predicts distinct domain opening transition mechanism for the domains of CaM. This is a surprising result because the domains have the same folded state topology. In the simulations, I find the two domains of CaM have distinct transition mechanism over a broad range of temperature, in harmony with the analytic predictions. In particular, the simulated transition mechanism of nCaM follows a two-state behavior, while domain opening in cCaM involves global unfolding and refolding of the tertiary structure. The unfolded intermediate also appears in the landscape of nCaM, but at a higher temperature than it appears in cCaM's energy landscape. This is consistent with nCaM's higher thermal stability. Under approximate physiological conditions, majority of the sampled transitions in cCaM involves unfolding and refolding during conformational change. Kinetically, the transient unfolding and refolding in cCaM significantly slows the domain opening and closing rates in cCaM. Second, I investigate the structural origins of binding affinity and allosteric cooperativity of binding 2 calcium-ions to each domain of CaM. In my work, I predict the order of binding strength of CaM's loops. I analyze simulated binding curves within the framework of the classic Monod-Wyman-Changeux (MWC) model of allostery to extract the binding free energies to the closed and open ensembles. The simulations predict that cCaM binds calcium with higher affinity and greater cooperativity than nCaM. Where it is possible to compare, these predictions are in good agreement with experimental results. The analysis of the simulations offers a rationale for why the two domains differ in cooperativity: the higher cooperativity of cCaM is due to larger difference in affinity of its binding loops. Third, I extend the work to investigate structural origins of binding cooperativity of 4 calcium-ions to intact CaM. I characterize the microscopic cooperativities of each ligation state and provide a kinetic description of the binding mechanism. Due to the heterogeneous nature of CaM's loops, as predicted in our simulations of isolated domains, I focus on investigating the influence of this heterogeneity on the kinetic flux of binding pathways as a function of concentration. The formalism developed for Network Models of protein folding kinetics, is used to evaluate the directed flux of all possible pathways between unligated and fully loaded CaM. (Abstract shortened by ProQuest.).

A comparison of physician implicit racial bias towards adults versus children

PubMed Central

Johnson, Tiffani J.; Winger, Daniel G.; Hickey, Robert W.; Switzer, Galen E.; Miller, Elizabeth; Nguyen, Margaret B.; Saladino, Richard A.; Hausmann, Leslie R. M.

2016-01-01

Background and Objectives The general population and most physicians have implicit racial bias against black adults. Pediatricians also have implicit bias against black adults, albeit less than other specialties. There is no published research on the implicit racial attitudes of pediatricians or other physicians towards children. Our objectives were to compare implicit racial bias towards adults versus children among resident physicians working in a pediatric emergency department (ED), and to assess whether bias varied by specialty (pediatrics, emergency medicine, or other), gender, race, age, and year of training. Methods We measured implicit racial bias of residents before a pediatric ED shift using the Adult and Child Race Implicit Association Tests (IATs). Generalized linear models compared Adult and Child IAT scores and determined the association of participant demographics with Adult and Child IAT scores. Results Among 91 residents, we found moderate pro-white/anti-black bias on both the Adult (M=0.49, SD=0.34) and Child Race IAT (M=0.55, SD=0.37). There was no significant difference between Adult and Child Race IAT scores (difference=0.06, p=0.15). Implicit bias was not associated with resident demographic characteristics, including specialty. Conclusions This is the first study demonstrating that resident physicians have implicit racial bias against black children, similar to levels of bias against black adults. Bias in our study did not vary by resident demographic characteristics, including specialty, suggesting that pediatric residents are as susceptible as other physicians to implicit bias. Future studies are needed to explore how physicians’ implicit attitudes towards parents and children may impact inequities in pediatric healthcare. PMID:27620844

Examining the Implicit Relational Assessment Procedure: Four Preliminary Studies

ERIC Educational Resources Information Center

Drake, Chad E.; Kellum, Karen Kate; Wilson, Kelly G.; Luoma, Jason B.; Weinstein, Jonathan H.; Adams, Catherine H.

2010-01-01

The Implicit Relational Assessment Procedure (IRAP) is a relatively new measure of implicit cognition that tests cognition as relational behavior instead of an associative activity and thus may provide a more specific measure of cognitive repertoires, including those for social biases, than better known implicit measures such as the Implicit…

Explicit versus Implicit Stereotypes: "What Biases Do I Really Hold?"

ERIC Educational Resources Information Center

Morgan, Melanie

2008-01-01

This article presents an activity in which students explore the impact of implicit stereotypes in everyday interactions while examining issues of attitudinal measurement. Social cognitions that underlie stereotypes often operate implicitly and even unconsciously. Consequently, these implicit attitudes have the potential to affect the way people…

Implicit Referential Meaning with Reference to English Arabic Translation

ERIC Educational Resources Information Center

Al-Zughoul, Basem

2014-01-01

The purpose of this study is to investigate how English implicit referential meaning is translated into Arabic by analyzing sentences containing implicit referential meanings found in the novel "Harry Potter and the Prisoner of Azkaban". The analysis shows that the translation of English implicit referential meaning into Arabic can be…

Chinese Undergraduates' Explicit and Implicit Attitudes toward Persons with Disabilities

ERIC Educational Resources Information Center

Chen, Shuang; Ma, Li; Zhang, Jian-Xin

2011-01-01

The present study is aimed at examining implicit and explicit attitudes toward persons with disabilities among Chinese college students. The "Implicit Association Test" was used to measure their implicit attitudes, whereas their explicit attitudes toward persons with disabilities were measured by using a scale of three items.…

Integrating sampling techniques and inverse virtual screening: toward the discovery of artificial peptide-based receptors for ligands.

PubMed

Pérez, Germán M; Salomón, Luis A; Montero-Cabrera, Luis A; de la Vega, José M García; Mascini, Marcello

2016-05-01

A novel heuristic using an iterative select-and-purge strategy is proposed. It combines statistical techniques for sampling and classification by rigid molecular docking through an inverse virtual screening scheme. This approach aims to the de novo discovery of short peptides that may act as docking receptors for small target molecules when there are no data available about known association complexes between them. The algorithm performs an unbiased stochastic exploration of the sample space, acting as a binary classifier when analyzing the entire peptides population. It uses a novel and effective criterion for weighting the likelihood of a given peptide to form an association complex with a particular ligand molecule based on amino acid sequences. The exploratory analysis relies on chemical information of peptides composition, sequence patterns, and association free energies (docking scores) in order to converge to those peptides forming the association complexes with higher affinities. Statistical estimations support these results providing an association probability by improving predictions accuracy even in cases where only a fraction of all possible combinations are sampled. False positives/false negatives ratio was also improved with this method. A simple rigid-body docking approach together with the proper information about amino acid sequences was used. The methodology was applied in a retrospective docking study to all 8000 possible tripeptide combinations using the 20 natural amino acids, screened against a training set of 77 different ligands with diverse functional groups. Afterward, all tripeptides were screened against a test set of 82 ligands, also containing different functional groups. Results show that our integrated methodology is capable of finding a representative group of the top-scoring tripeptides. The associated probability of identifying the best receptor or a group of the top-ranked receptors is more than double and about 10 times higher, respectively, when compared to classical random sampling methods.

NUEN-618 Class Project: Actually Implicit Monte Carlo

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vega, R. M.; Brunner, T. A.

2017-12-14

This research describes a new method for the solution of the thermal radiative transfer (TRT) equations that is implicit in time which will be called Actually Implicit Monte Carlo (AIMC). This section aims to introduce the TRT equations, as well as the current workhorse method which is known as Implicit Monte Carlo (IMC). As the name of the method proposed here indicates, IMC is a misnomer in that it is only semi-implicit, which will be shown in this section as well.

Molecular Dynamics in Mixed Solvents Reveals Protein-Ligand Interactions, Improves Docking, and Allows Accurate Binding Free Energy Predictions.

PubMed

Arcon, Juan Pablo; Defelipe, Lucas A; Modenutti, Carlos P; López, Elias D; Alvarez-Garcia, Daniel; Barril, Xavier; Turjanski, Adrián G; Martí, Marcelo A

2017-04-24

One of the most important biological processes at the molecular level is the formation of protein-ligand complexes. Therefore, determining their structure and underlying key interactions is of paramount relevance and has direct applications in drug development. Because of its low cost relative to its experimental sibling, molecular dynamics (MD) simulations in the presence of different solvent probes mimicking specific types of interactions have been increasingly used to analyze protein binding sites and reveal protein-ligand interaction hot spots. However, a systematic comparison of different probes and their real predictive power from a quantitative and thermodynamic point of view is still missing. In the present work, we have performed MD simulations of 18 different proteins in pure water as well as water mixtures of ethanol, acetamide, acetonitrile and methylammonium acetate, leading to a total of 5.4 μs simulation time. For each system, we determined the corresponding solvent sites, defined as space regions adjacent to the protein surface where the probability of finding a probe atom is higher than that in the bulk solvent. Finally, we compared the identified solvent sites with 121 different protein-ligand complexes and used them to perform molecular docking and ligand binding free energy estimates. Our results show that combining solely water and ethanol sites allows sampling over 70% of all possible protein-ligand interactions, especially those that coincide with ligand-based pharmacophoric points. Most important, we also show how the solvent sites can be used to significantly improve ligand docking in terms of both accuracy and precision, and that accurate predictions of ligand binding free energies, along with relative ranking of ligand affinity, can be performed.

The influence of citrate and oxalate on 99TcVII, Cs, NpV and UVI sorption to a Savannah River Site soil.

PubMed

Montgomery, D; Barber, K; Edayilam, N; Oqujiuba, K; Young, S; Biotidara, T; Gathers, A; Danjaji, M; Tharayil, N; Martinez, N; Powell, B

2017-06-01

Batch sorption experiments were conducted with 0.5-50 ppb 99 Tc, 133 Cs, 237 Np and U in the presence and absence of citrate and/or oxalate in a 25 g/L Savannah River Site (SRS) soil suspension. Citrate and oxalate were the ligands of choice due to their relevancy to plant exudates, the nuclides were selected for their wide range of biogeochemical behavior, and the soil from SRS was selected as a model Department of Energy (DOE) site soil. Batch samples were continually mixed on a rotary shaker and maintained at a pH of approximately 5. Analysis via ICP-MS indicated that sorption of 237 Np increased with ligand concentration compared to baseline studies, as did sorption of 99 Tc although to a lesser extent. The increased sorption of 237 Np is proposed to be due to a combination of factors that are dependent on the ligand(s) present in the specific system including, ligand dissolution of the soil by citrate and formation of tertiary soil-oxalate-Np complexes. The increased 99 Tc sorption is attributed to the dissolution of the soil by the ligands, leading to an increase in the number of available sorption sites for 99 Tc. Uranium sorption decreased and dissolution of native uranium was also observed with increasing ligand concentration, thought to be a result of the formation of strong U-ligand complexes remaining in the aqueous phase. The majority of these effects were observed at the highest ligand concentrations of 50 mg C /L. No notable changes were observed for the 133 Cs system which is ascribed to the minimal interaction of Cs + with these organic ligands. Copyright © 2017 Elsevier Ltd. All rights reserved.

Efficient implementation of constant pH molecular dynamics on modern graphics processors.

PubMed

Arthur, Evan J; Brooks, Charles L

2016-09-15

The treatment of pH sensitive ionization states for titratable residues in proteins is often omitted from molecular dynamics (MD) simulations. While static charge models can answer many questions regarding protein conformational equilibrium and protein-ligand interactions, pH-sensitive phenomena such as acid-activated chaperones and amyloidogenic protein aggregation are inaccessible to such models. Constant pH molecular dynamics (CPHMD) coupled with the Generalized Born with a Simple sWitching function (GBSW) implicit solvent model provide an accurate framework for simulating pH sensitive processes in biological systems. Although this combination has demonstrated success in predicting pKa values of protein structures, and in exploring dynamics of ionizable side-chains, its speed has been an impediment to routine application. The recent availability of low-cost graphics processing unit (GPU) chipsets with thousands of processing cores, together with the implementation of the accurate GBSW implicit solvent model on those chipsets (Arthur and Brooks, J. Comput. Chem. 2016, 37, 927), provide an opportunity to improve the speed of CPHMD and ionization modeling greatly. Here, we present a first implementation of GPU-enabled CPHMD within the CHARMM-OpenMM simulation package interface. Depending on the system size and nonbonded force cutoff parameters, we find speed increases of between one and three orders of magnitude. Additionally, the algorithm scales better with system size than the CPU-based algorithm, thus allowing for larger systems to be modeled in a cost effective manner. We anticipate that the improved performance of this methodology will open the door for broad-spread application of CPHMD in its modeling pH-mediated biological processes. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Method of detecting luminescent target ions with modified magnetic microspheres

DOEpatents

Shkrob, Ilya A; Kaminski, Michael D

2014-05-13

This invention provides methods of using modified magnetic microspheres to extract target ions from a sample in order to detect their presence in a microfluidic environment. In one or more embodiments, the microspheres are modified with molecules on the surface that allow the target ions in the sample to form complexes with specific ligand molecules on the microsphere surface. In one or more embodiments, the microspheres are modified with molecules that sequester the target ions from the sample, but specific ligand molecules in solution subsequently re-extract the target ions from the microspheres into the solution, where the complexes form independent of the microsphere surface. Once the complexes form, they are exposed to an excitation wavelength light source suitable for exciting the target ion to emit a luminescent signal pattern. Detection of the luminescent signal pattern allows for determination of the presence of the target ions in the sample.

Implicit social cognition: From measures to mechanisms

PubMed Central

Nosek, Brian A.; Hawkins, Carlee Beth; Frazier, Rebecca S.

2011-01-01

Most of human cognition occurs outside of conscious awareness or conscious control. Some of these implicit processes influence social perception, judgment and action. The last fifteen years of research in implicit social cognition can be characterized as the Age of Measurement because of a proliferation of measurement methods and research evidence demonstrating their practical value for predicting human behavior. Implicit measures assess constructs that are distinct, but related, to self-report assessments, and predict variation in behavior that is not accounted for by those explicit measures. The present state of knowledge provides a foundation for the next age of implicit social cognition – clarification of the mechanisms underlying implicit measurement and how the measured constructs influence behavior. PMID:21376657

Implicit and semi-implicit schemes in the Versatile Advection Code: numerical tests

NASA Astrophysics Data System (ADS)

Toth, G.; Keppens, R.; Botchev, M. A.

1998-04-01

We describe and evaluate various implicit and semi-implicit time integration schemes applied to the numerical simulation of hydrodynamical and magnetohydrodynamical problems. The schemes were implemented recently in the software package Versatile Advection Code, which uses modern shock capturing methods to solve systems of conservation laws with optional source terms. The main advantage of implicit solution strategies over explicit time integration is that the restrictive constraint on the allowed time step can be (partially) eliminated, thus the computational cost is reduced. The test problems cover one and two dimensional, steady state and time accurate computations, and the solutions contain discontinuities. For each test, we confront explicit with implicit solution strategies.

Improving virtual screening of G protein-coupled receptors via ligand-directed modeling

PubMed Central

Simms, John; Christopoulos, Arthur; Wootten, Denise

2017-01-01

G protein-coupled receptors (GPCRs) play crucial roles in cell physiology and pathophysiology. There is increasing interest in using structural information for virtual screening (VS) of libraries and for structure-based drug design to identify novel agonist or antagonist leads. However, the sparse availability of experimentally determined GPCR/ligand complex structures with diverse ligands impedes the application of structure-based drug design (SBDD) programs directed to identifying new molecules with a select pharmacology. In this study, we apply ligand-directed modeling (LDM) to available GPCR X-ray structures to improve VS performance and selectivity towards molecules of specific pharmacological profile. The described method refines a GPCR binding pocket conformation using a single known ligand for that GPCR. The LDM method is a computationally efficient, iterative workflow consisting of protein sampling and ligand docking. We developed an extensive benchmark comparing LDM-refined binding pockets to GPCR X-ray crystal structures across seven different GPCRs bound to a range of ligands of different chemotypes and pharmacological profiles. LDM-refined models showed improvement in VS performance over origin X-ray crystal structures in 21 out of 24 cases. In all cases, the LDM-refined models had superior performance in enriching for the chemotype of the refinement ligand. This likely contributes to the LDM success in all cases of inhibitor-bound to agonist-bound binding pocket refinement, a key task for GPCR SBDD programs. Indeed, agonist ligands are required for a plethora of GPCRs for therapeutic intervention, however GPCR X-ray structures are mostly restricted to their inactive inhibitor-bound state. PMID:29131821

ITC-derived binding affinity may be biased due to titrant (nano)-aggregation. Binding of halogenated benzotriazoles to the catalytic domain of human protein kinase CK2

PubMed Central

Winiewska, Maria; Bugajska, Ewa

2017-01-01

The binding of four bromobenzotriazoles to the catalytic subunit of human protein kinase CK2 was assessed by two complementary methods: Microscale Thermophoresis (MST) and Isothermal Titration Calorimetry (ITC). New algorithm proposed for the global analysis of MST pseudo-titration data enabled reliable determination of binding affinities for two distinct sites, a relatively strong one with the Kd of the order of 100 nM and a substantially weaker one (Kd > 1 μM). The affinities for the strong binding site determined for the same protein-ligand systems using ITC were in most cases approximately 10-fold underestimated. The discrepancy was assigned directly to the kinetics of ligand nano-aggregates decay occurring upon injection of the concentrated ligand solution to the protein sample. The binding affinities determined in the reverse ITC experiment, in which ligands were titrated with a concentrated protein solution, agreed with the MST-derived data. Our analysis suggests that some ITC-derived Kd values, routinely reported together with PDB structures of protein-ligand complexes, may be biased due to the uncontrolled ligand (nano)-aggregation, which may occur even substantially below the solubility limit. PMID:28273138

Implicit memory. Retention without remembering.

PubMed

Roediger, H L

1990-09-01

Explicit measures of human memory, such as recall or recognition, reflect conscious recollection of the past. Implicit tests of retention measure transfer (or priming) from past experience on tasks that do not require conscious recollection of recent experiences for their performance. The article reviews research on the relation between explicit and implicit memory. The evidence points to substantial differences between standard explicit and implicit tests, because many variables create dissociations between these tests. For example, although pictures are remembered better than words on explicit tests, words produce more priming than do pictures on several implicit tests. These dissociations may implicate different memory systems that subserve distinct memorial functions, but the present argument is that many dissociations can be understood by appealing to general principles that apply to both explicit and implicit tests. Phenomena studied under the rubric of implicit memory may have important implications in many other fields, including social cognition, problem solving, and cognitive development.

Terror management theory and self-esteem revisited: the roles of implicit and explicit self-esteem in mortality salience effects.

PubMed

Schmeichel, Brandon J; Gailliot, Matthew T; Filardo, Emily-Ana; McGregor, Ian; Gitter, Seth; Baumeister, Roy F

2009-05-01

Three studies tested the roles of implicit and/or explicit self-esteem in reactions to mortality salience. In Study 1, writing about death versus a control topic increased worldview defense among participants low in implicit self-esteem but not among those high in implicit self-esteem. In Study 2, a manipulation to boost implicit self-esteem reduced the effect of mortality salience on worldview defense. In Study 3, mortality salience increased the endorsement of positive personality descriptions but only among participants with the combination of low implicit and high explicit self-esteem. These findings indicate that high implicit self-esteem confers resilience against the psychological threat of death, and therefore the findings provide direct support for a fundamental tenet of terror management theory regarding the anxiety-buffering role of self-esteem. Copyright (c) 2009 APA, all rights reserved.

Moderators of Implicit-Explicit Exercise Cognition Concordance.

PubMed

Berry, Tanya R; Rodgers, Wendy M; Markland, David; Hall, Craig R

2016-12-01

Investigating implicit-explicit concordance can aid in understanding underlying mechanisms and possible intervention effects. This research examined the concordance between implicit associations of exercise with health or appearance and related explicit motives. Variables considered as possible moderators were behavioral regulations, explicit attitudes, and social desirability. Participants (N = 454) completed measures of implicit associations of exercise with health and appearance and questionnaire measures of health and appearance motives, attitudes, social desirability, and behavioral regulations. Attitudes significantly moderated the relationship between implicit associations of exercise with health and health motives. Identified regulations significantly moderated implicit-explicit concordance with respect to associations with appearance. These results suggest that implicit and explicit exercise-related cognitions are not necessarily independent and their relationship to each other may be moderated by attitudes or some forms of behavioral regulation. Future research that takes a dual-processing approach to exercise behavior should consider potential theoretical moderators of concordance.

How Explicit and Implicit Test Instructions in an Implicit Learning Task Affect Performance

PubMed Central

Witt, Arnaud; Puspitawati, Ira; Vinter, Annie

2013-01-01

Typically developing children aged 5 to 8 years were exposed to artificial grammar learning. Following an implicit exposure phase, half of the participants received neutral instructions at test while the other half received instructions making a direct, explicit reference to the training phase. We first aimed to assess whether implicit learning operated in the two test conditions. We then evaluated the differential impact of age on learning performances as a function of test instructions. The results showed that performance did not vary as a function of age in the implicit instructions condition, while age effects emerged when explicit instructions were employed at test. However, performance was affected differently by age and the instructions given at test, depending on whether the implicit learning of short or long units was assessed. These results suggest that the claim that the implicit learning process is independent of age needs to be revised. PMID:23326409

Do Implicit Attitudes Predict Actual Voting Behavior Particularly for Undecided Voters?

PubMed Central

Friese, Malte; Smith, Colin Tucker; Plischke, Thomas; Bluemke, Matthias; Nosek, Brian A.

2012-01-01

The prediction of voting behavior of undecided voters poses a challenge to psychologists and pollsters. Recently, researchers argued that implicit attitudes would predict voting behavior particularly for undecided voters whereas explicit attitudes would predict voting behavior particularly for decided voters. We tested this assumption in two studies in two countries with distinct political systems in the context of real political elections. Results revealed that (a) explicit attitudes predicted voting behavior better than implicit attitudes for both decided and undecided voters, and (b) implicit attitudes predicted voting behavior better for decided than undecided voters. We propose that greater elaboration of attitudes produces stronger convergence between implicit and explicit attitudes resulting in better predictive validity of both, and less incremental validity of implicit over explicit attitudes for the prediction of voting behavior. However, greater incremental predictive validity of implicit over explicit attitudes may be associated with less elaboration. PMID:22952898

Fast, metadynamics-based method for prediction of the stereochemistry-dependent relative free energies of ligand-receptor interactions.

PubMed

Plazinska, Anita; Plazinski, Wojciech; Jozwiak, Krzysztof

2014-04-30

The computational approach applicable for the molecular dynamics (MD)-based techniques is proposed to predict the ligand-protein binding affinities dependent on the ligand stereochemistry. All possible stereoconfigurations are expressed in terms of one set of force-field parameters [stereoconfiguration-independent potential (SIP)], which allows for calculating all relative free energies by only single simulation. SIP can be used for studying diverse, stereoconfiguration-dependent phenomena by means of various computational techniques of enhanced sampling. The method has been successfully tested on the β2-adrenergic receptor (β2-AR) binding the four fenoterol stereoisomers by both metadynamics simulations and replica-exchange MD. Both the methods gave very similar results, fully confirming the presence of stereoselective effects in the fenoterol-β2-AR interactions. However, the metadynamics-based approach offered much better efficiency of sampling which allows for significant reduction of the unphysical region in SIP. Copyright © 2014 Wiley Periodicals, Inc.

Free energy landscape of protein folding in water: explicit vs. implicit solvent.

PubMed

Zhou, Ruhong

2003-11-01

The Generalized Born (GB) continuum solvent model is arguably the most widely used implicit solvent model in protein folding and protein structure prediction simulations; however, it still remains an open question on how well the model behaves in these large-scale simulations. The current study uses the beta-hairpin from C-terminus of protein G as an example to explore the folding free energy landscape with various GB models, and the results are compared to the explicit solvent simulations and experiments. All free energy landscapes are obtained from extensive conformation space sampling with a highly parallel replica exchange method. Because solvation model parameters are strongly coupled with force fields, five different force field/solvation model combinations are examined and compared in this study, namely the explicit solvent model: OPLSAA/SPC model, and the implicit solvent models: OPLSAA/SGB (Surface GB), AMBER94/GBSA (GB with Solvent Accessible Surface Area), AMBER96/GBSA, and AMBER99/GBSA. Surprisingly, we find that the free energy landscapes from implicit solvent models are quite different from that of the explicit solvent model. Except for AMBER96/GBSA, all other implicit solvent models find the lowest free energy state not the native state. All implicit solvent models show erroneous salt-bridge effects between charged residues, particularly in OPLSAA/SGB model, where the overly strong salt-bridge effect results in an overweighting of a non-native structure with one hydrophobic residue F52 expelled from the hydrophobic core in order to make better salt bridges. On the other hand, both AMBER94/GBSA and AMBER99/GBSA models turn the beta-hairpin in to an alpha-helix, and the alpha-helical content is much higher than the previously reported alpha-helices in an explicit solvent simulation with AMBER94 (AMBER94/TIP3P). Only AMBER96/GBSA shows a reasonable free energy landscape with the lowest free energy structure the native one despite an erroneous salt-bridge between D47 and K50. Detailed results on free energy contour maps, lowest free energy structures, distribution of native contacts, alpha-helical content during the folding process, NOE comparison with NMR, and temperature dependences are reported and discussed for all five models. Copyright 2003 Wiley-Liss, Inc.

The Implicit Relational Assessment Procedure (IRAP) as a Measure of Spider Fear

ERIC Educational Resources Information Center

Nicholson, Emma; Barnes-Holmes, Dermot

2012-01-01

A greater understanding of implicit cognition can provide important information regarding the etiology and maintenance of psychological disorders. The current study sought to determine the utility of the Implicit Relational Assessment Procedure (IRAP) as a measure of implicit aversive bias toward spiders in two groups of known variation, high fear…

Implicit and Explicit Memory for Affective Passages in Temporal Lobectomy Patients

ERIC Educational Resources Information Center

Burton, Leslie A.; Rabin, Laura; Vardy, Susan Bernstein; Frohlich, Jonathan; Porter, Gwinne Wyatt; Dimitri, Diana; Cofer, Lucas; Labar, Douglas

2008-01-01

Eighteen temporal lobectomy patients (9 left, LTL; 9 right, RTL) were administered four verbal tasks, an Affective Implicit Task, a Neutral Implicit Task, an Affective Explicit Task, and a Neutral Explicit Task. For the Affective and Neutral Implicit Tasks, participants were timed while reading aloud passages with affective or neutral content,…

The Pivotal Role of Effort Beliefs in Mediating Implicit Theories of Intelligence and Achievement Goals and Academic Motivations

ERIC Educational Resources Information Center

Tempelaar, Dirk T.; Rienties, Bart; Giesbers, Bas; Gijselaers, Wim H.

2015-01-01

Empirical studies into meaning systems surrounding implicit theories of intelligence typically entail two stringent assumptions: that different implicit theories and different effort beliefs represent opposite poles on a single scale, and that implicit theories directly impact the constructs as achievement goals and academic motivations. Through…

Friendships Influence Hispanic Students' Implicit Attitudes toward White Non-Hispanics Relative to African Americans

ERIC Educational Resources Information Center

Aberson, Christopher L.; Porter, Michael K.; Gaffney, Amber M.

2008-01-01

This study examined the role of Hispanic students' friendships with White non-Hispanics (n-Hs) and African Americans (AAs) in predicting implicit and explicit prejudices toward these groups. Participants (N = 73) completed implicit and explicit attitude measures and a friendship questionnaire. Friendships were associated with implicit attitudes…

Do College Instructors Have Implicit Bias toward Latino-Accented English Speakers?

ERIC Educational Resources Information Center

Na, Eunkyung

2016-01-01

The purpose of this study was to examine the implicit attitudes of college-level instructors toward Latino-accented English and the effects of gender, teaching experience, home language, race/ethnicity, and rank on those attitudes. The auditory Implicit Association Test (IAT) was used to measure the implicit accent preferences. Participants (N =…

The Effects of Mindfulness versus Thought Suppression on Implicit and Explicit Measures of Experiential Avoidance

ERIC Educational Resources Information Center

Hooper, Nic; Villatte, Matthieu; Neofotistou, Evi; McHugh, Louise

2010-01-01

The current study aimed to provide an implicit measure of experiential avoidance (EA). Fifty undergraduate participants were exposed to an implicit (Implicit Relational Assessment Procedure: IRAP) and an explicit (Acceptance and Action Questionnaire II: AAQ II) measure of EA. Subsequently participant's response latencies on viewing a negatively…

Explicit and Implicit Stigma of Mental Illness as Predictors of the Recovery Attitudes of Assertive Community Treatment Practitioners.

PubMed

Stull, Laura G; McConnell, Haley; McGrew, John; Salyers, Michelle P

2017-01-01

While explicit negative stereotypes of mental illness are well established as barriers to recovery, implicit attitudes also may negatively impact outcomes. The current study is unique in its focus on both explicit and implicit stigma as predictors of recovery attitudes of mental health practitioners. Assertive Community Treatment practitioners (n = 154) from 55 teams completed online measures of stigma, recovery attitudes, and an Implicit Association Test (IAT). Three of four explicit stigma variables (perceptions of blameworthiness, helplessness, and dangerousness) and all three implicit stigma variables were associated with lower recovery attitudes. In a multivariate, hierarchical model, however, implicit stigma did not explain additional variance in recovery attitudes. In the overall model, perceptions of dangerousness and implicitly associating mental illness with "bad" were significant individual predictors of lower recovery attitudes. The current study demonstrates a need for interventions to lower explicit stigma, particularly perceptions of dangerousness, to increase mental health providers' expectations for recovery. The extent to which implicit and explicit stigma differentially predict outcomes, including recovery attitudes, needs further research.

How "implicit" are implicit color effects in memory?

PubMed

Zimmer, Hubert D; Steiner, Astrid; Ecker, Ullrich K H

2002-01-01

Processing colored pictures of objects results in a preference to choose the former color for a specific object in a subsequent color choice test (Wippich & Mecklenbräuker, 1998). We tested whether this implicit memory effect is independent of performances in episodic color recollection (recognition). In the study phase of Experiment 1, the color of line drawings was either named or its appropriateness was judged. We found only weak implicit memory effects for categorical color information. In Experiment 2, silhouettes were colored by subjects during the study phase. Performances in both the implicit and the explicit test were good. Selections of "old" colors in the implicit test, though, were almost completely confined to items for which the color was also remembered explicitly. In Experiment 3, we applied the opposition technique in order to check whether we could find any implicit effects regarding items for which no explicit color recollection was possible. This was not the case. We therefore draw the conclusion that implicit color preference effects are not independent of explicit recollection, and that they are probably based on the same episodic memory traces that are used in explicit tests.

The moderating role of implicit alcohol-related cognitions in hazardous alcohol use

PubMed Central

Cavanagh, Lucia; Obasi, Ezemenari M.

2015-01-01

The present study applied the Go/No-Go Association Test (GNAT; Nosek & Banaji, 2001) to measure alcohol-related implicit cognitions. Additionally, it assessed the role of implicit cognitions as a potential moderator in the relationship between explicit predictors of alcohol use and hazardous drinking behavior. University undergraduate students (N = 214) completed self-report questionnaires assessing reasons for drinking and reported alcohol use. Participants also completed two GNATs assessing implicit-alcohol-related cognitions associated with attitude (good-bad) and perceived safety (safe-dangerous). As expected, participants held implicit appraisals of alcohol as ‘‘bad’’ and ‘‘dangerous’’ in the context of nonalcoholic drinks, and as ‘‘good’’ and ‘‘safe’’ in the context of licit and illicit drugs. Implicit alcohol-related cognitions moderated the relationship between drinking to cope with negative affect and hazardous drinking and drinking due to cues or craving and hazardous drinking. These findings highlight the multidimensional nature of implicit cognitions and the role of negative implicit alcohol-related associations in moderating relationships between explicit processes and subsequent alcohol use behaviors. PMID:26989352

Iterative refinement of implicit boundary models for improved geological feature reproduction

NASA Astrophysics Data System (ADS)

Martin, Ryan; Boisvert, Jeff B.

2017-12-01

Geological domains contain non-stationary features that cannot be described by a single direction of continuity. Non-stationary estimation frameworks generate more realistic curvilinear interpretations of subsurface geometries. A radial basis function (RBF) based implicit modeling framework using domain decomposition is developed that permits introduction of locally varying orientations and magnitudes of anisotropy for boundary models to better account for the local variability of complex geological deposits. The interpolation framework is paired with a method to automatically infer the locally predominant orientations, which results in a rapid and robust iterative non-stationary boundary modeling technique that can refine locally anisotropic geological shapes automatically from the sample data. The method also permits quantification of the volumetric uncertainty associated with the boundary modeling. The methodology is demonstrated on a porphyry dataset and shows improved local geological features.

Production Functions for Water Delivery Systems: Analysis and Estimation Using Dual Cost Function and Implicit Price Specifications

NASA Astrophysics Data System (ADS)

Teeples, Ronald; Glyer, David

1987-05-01

Both policy and technical analysis of water delivery systems have been based on cost functions that are inconsistent with or are incomplete representations of the neoclassical production functions of economics. We present a full-featured production function model of water delivery which can be estimated from a multiproduct, dual cost function. The model features implicit prices for own-water inputs and is implemented as a jointly estimated system of input share equations and a translog cost function. Likelihood ratio tests are performed showing that a minimally constrained, full-featured production function is a necessary specification of the water delivery operations in our sample. This, plus the model's highly efficient and economically correct parameter estimates, confirms the usefulness of a production function approach to modeling the economic activities of water delivery systems.

Cultural Variations in Mothers' Acceptance of and Intent to Use Behavioral Child Management Techniques

ERIC Educational Resources Information Center

Mah, Janet W. T.; Johnston, Charlotte

2012-01-01

We examined cultural differences in mothers' acceptance of and intent to use behavioral parenting techniques for managing disruptive child behavior, and the possible roles of parenting styles and implicit theories in explaining these cultural differences. A community sample of 117 Euro-Canadian and Chinese-immigrant mothers of boys aged 4- to…

Wealth, Income, and Price Effects in Local School Finance.

ERIC Educational Resources Information Center

Grubb, W. Norton

In this paper, the author attempts to clarify several implicit hypotheses about local school finance reform, set up tests whereby hypothesis validity can be affirmed or rejected, and outline the policy implications of the results. Two mathematical models of school district behavior are examined, and their implications are tested on a sample of 150…

Rethinking UK Small Employers' Skills Policies and the Role of Workplace Learning

ERIC Educational Resources Information Center

Kitching, John

2008-01-01

Small business employers in the UK are widely perceived as adopting a reactive, ad hoc approach to employee skill formation. Employer reliance on workplace learning is often treated, explicitly or implicitly, as evidence of such an approach. Small employers' approaches to skill creation are investigated using data from two employer samples. Three…

The Procedural Learning Deficit Hypothesis of Language Learning Disorders: We See Some Problems

ERIC Educational Resources Information Center

West, Gillian; Vadillo, Miguel A.; Shanks, David R.; Hulme, Charles

2018-01-01

Impaired procedural learning has been suggested as a possible cause of developmental dyslexia (DD) and specific language impairment (SLI). This study examined the relationship between measures of verbal and non-verbal implicit and explicit learning and measures of language, literacy and arithmetic attainment in a large sample of 7 to 8-year-old…

Factor Structure, Stability, and Congruence in the Functional Movement Screen

ERIC Educational Resources Information Center

Kelleher, Leila K.; Beach, Tyson A. C.; Frost, David M.; Johnson, Andrew M.; Dickey, James P.

2018-01-01

The scoring scheme for the functional movement screen implicitly assumes that the factor structure is consistent, stable, and congruent across different populations. To determine if this is the case, we compared principal components analyses of three samples: a healthy, general population (n = 100), a group of varsity athletes (n = 101), and a…

The Role of Education in Development of Wisdom

ERIC Educational Resources Information Center

Ambrosi-Randic, Neala; Plavšic, Marlena

2015-01-01

In order to explore the potential role of education in wisdom development two independent studies were done. The main goal of the first study was focused on exploring some aspects of implicit theories of wisdom. For the purpose of this research authors have constructed The "Questionnaire on Wisdom" and applied it on a sample of 259…

An Implicit Theories of Personality Intervention Reduces Adolescent Aggression in Response to Victimization and Exclusion

ERIC Educational Resources Information Center

Yeager, David Scott; Trzesniewski, Kali H.; Dweck, Carol S.

2013-01-01

Adolescents are often resistant to interventions that reduce aggression in children. At the same time, they are developing stronger beliefs in the fixed nature of personal characteristics, particularly aggression. The present intervention addressed these beliefs. A randomized field experiment with a diverse sample of Grades 9 and 10 students (ages…

Why Women Want to Work: A Look at Career Persistence.

ERIC Educational Resources Information Center

Mandelbaum, Dorothy Rosenthal

The notions of both work and persistence carry implicit assumptions that some obstacles have to be overcome through effort. Given the hurdles that women physicians must overcome in training, most research has assumed that work plays an important role in their lives. A sample of 71 women physicians from an earlier study was surveyed to learn why…

Alternative Factor Models and Heritability of the Short Leyton Obsessional Inventory--Children's Version

ERIC Educational Resources Information Center

Moore, Janette; Smith, Gillian W.; Shevlin, Mark; O'Neill, Francis A.

2010-01-01

An alternative models framework was used to test three confirmatory factor analytic models for the Short Leyton Obsessional Inventory-Children's Version (Short LOI-CV) in a general population sample of 517 young adolescent twins (11-16 years). A one-factor model as implicit in current classification systems of Obsessive-Compulsive Disorder (OCD),…

Ocean Data Assimilation: A Coastal Application

DTIC Science & Technology

2009-01-01

tcchnique with a semi-implicit formulation for the vertical acoustic modes (Ho- dur 1997; Hodur et al. 2002; Doyle et al. 2(08). A Robert time filter...r;,d i<l tion pyrometer was used to me<lsure SST with O. loe precision and O.SoC absolute ;Iccuracy. Sample ::l ircrllft p;Jths for J 3 August 2003

Controlled and implicit processes in evaluative conditioning on implicit and explicit attitudes toward alcohol and intentions to drink.

PubMed

Zerhouni, Oulmann; Bègue, Laurent; Comiran, Francisco; Wiers, Reinout W

2018-01-01

Since implicit attitudes (i.e. evaluations occurring outside of complete awareness) are highly predictive of alcohol consumption, we tested an evaluative learning procedure based on repeated pairing to a critical stimulus (i.e. alcohol, the CS) with a valenced stimulus (the US) in order to modify implicit attitudes (i.e. evaluative conditioning; EC). We hypothesized that manipulating the learning context to bolster implicit affect misattribution should strengthen EC effects on implicit attitudes toward alcohol, while encouraging deliberate processing of CS-US pairs, should strengthen EC effects on explicit attitudes. In our study (n=114 students) we manipulated whether CS-US pairs were presented simultaneously or sequentially. Recollective memory was estimated with a Process Dissociation Procedure. Both implicit and explicit attitudes were assessed immediately after the procedure. Behavioral intentions were measured directly after and one week after the EC-procedure. We found that EC with sequential presentation had a stronger impact on implicit and explicit measures and on purchase intentions immediately after the procedure and one week after. The present findings provide new evidence that (i) EC is an effective way to change implicit attitudes toward alcohol and (ii) evidence that EC may be better described by propositional rather than dual process accounts. Copyright © 2017 Elsevier Ltd. All rights reserved.

Implicit Weight Bias in Children Age 9 to 11 Years.

PubMed

Skinner, Asheley Cockrell; Payne, Keith; Perrin, Andrew J; Panter, Abigail T; Howard, Janna B; Bardone-Cone, Anna; Bulik, Cynthia M; Steiner, Michael J; Perrin, Eliana M

2017-07-01

Assess implicit weight bias in children 9 to 11 years old. Implicit weight bias was measured in children ages 9 to 11 ( N = 114) by using the Affect Misattribution Procedure. Participants were shown a test image of a child for 350 milliseconds followed by a meaningless fractal (200 milliseconds), and then they were asked to rate the fractal image as "good" or "bad." We used 9 image pairs matched on age, race, sex, and activity but differing by weight of the child. Implicit bias was the difference between positive ratings for fractals preceded by an image of a healthy-weight child and positive ratings for fractals preceded by an image of an overweight child. On average, 64% of abstract fractals shown after pictures of healthy-weight children were rated as "good," compared with 59% of those shown after pictures of overweight children, reflecting an overall implicit bias rate of 5.4% against overweight children ( P < .001). Healthy-weight participants showed greater implicit bias than over- and underweight participants (7.9%, 1.4%, and 0.3% respectively; P = .049). Implicit bias toward overweight individuals is evident in children aged 9 to 11 years with a magnitude of implicit bias (5.4%) similar to that in studies of implicit racial bias among adults. Copyright © 2017 by the American Academy of Pediatrics.

The influence of linguistic and cognitive factors on the time course of verb-based implicit causality.

PubMed

Koornneef, Arnout; Dotlačil, Jakub; van den Broek, Paul; Sanders, Ted

2016-01-01

In three eye-tracking experiments the influence of the Dutch causal connective "want" (because) and the working memory capacity of readers on the usage of verb-based implicit causality was examined. Experiments 1 and 2 showed that although a causal connective is not required to activate implicit causality information during reading, effects of implicit causality surfaced more rapidly and were more pronounced when a connective was present in the discourse than when it was absent. In addition, Experiment 3 revealed that-in contrast to previous claims-the activation of implicit causality is not a resource-consuming mental operation. Moreover, readers with higher and lower working memory capacities behaved differently in a dual-task situation. Higher span readers were more likely to use implicit causality when they had all their working memory resources at their disposal. Lower span readers showed the opposite pattern as they were more likely to use the implicit causality cue in the case of an additional working memory load. The results emphasize that both linguistic and cognitive factors mediate the impact of implicit causality on text comprehension. The implications of these results are discussed in terms of the ongoing controversies in the literature-that is, the focusing-integration debate and the debates on the source of implicit causality.

Implicit and explicit motor sequence learning in children born very preterm.

PubMed

Jongbloed-Pereboom, Marjolein; Janssen, Anjo J W M; Steiner, K; Steenbergen, Bert; Nijhuis-van der Sanden, Maria W G

2017-01-01

Motor skills can be learned explicitly (dependent on working memory (WM)) or implicitly (relatively independent of WM). Children born very preterm (VPT) often have working memory deficits. Explicit learning may be compromised in these children. This study investigated implicit and explicit motor learning and the role of working memory in VPT children and controls. Three groups (6-9 years) participated: 20 VPT children with motor problems, 20 VPT children without motor problems, and 20 controls. A nine button sequence was learned implicitly (pressing the lighted button as quickly as possible) and explicitly (discovering the sequence via trial-and-error). Children learned implicitly and explicitly, evidenced by decreased movement duration of the sequence over time. In the explicit condition, children also reduced the number of errors over time. Controls made more errors than VPT children without motor problems. Visual WM had positive effects on both explicit and implicit performance. VPT birth and low motor proficiency did not negatively affect implicit or explicit learning. Visual WM was positively related to both implicit and explicit performance, but did not influence learning curves. These findings question the theoretical difference between implicit and explicit learning and the proposed role of visual WM therein. Copyright © 2016 Elsevier Ltd. All rights reserved.

Assessment of implicit sexual associations in non-incarcerated pedophiles.

PubMed

van Leeuwen, Matthijs L; van Baaren, Rick B; Chakhssi, Farid; Loonen, Marijke G M; Lippman, Maarten; Dijksterhuis, Ap

2013-11-01

Offences committed by pedophiles are crimes that evoke serious public concern and outrage. Although recent research using implicit measures has shown promise in detecting deviant sexual associations, the discriminatory and predictive quality of implicit tasks has not yet surpassed traditional assessment methods such as questionnaires and phallometry. The current research extended previous findings by examining whether a combination of two implicit tasks, the Implicit Association Task (IAT) and the Picture Association Task (PAT), was capable of differentiating pedophiles from non-pedophiles, and whether the PAT, which allows separate analysis for male, female, boy and girl stimulus categories, was more sensitive to specific sexual associations in pedophiles than the IAT. A total of 20 male self-reported pedophiles (10 offender and 10 non-offenders) and 20 male self-reported heterosexual controls completed the two implicit measures. Results indicated that the combination of both tasks produced the strongest results to date in detecting implicit pedophilic preferences (AUC = .97). Additionally, the PAT showed promise in decomposing the sexual associations in pedophiles. Interestingly, as there was an equal distribution of offenders and non-offenders in the pedophile group, it was possible to test for implicit association differences between these groups. This comparison showed no clear link between having these implicit sexual associations and actual offending.

Implicit and explicit self-esteem as concurrent predictors of suicidal ideation, depressive symptoms, and loneliness.

PubMed

Creemers, Daan H M; Scholte, Ron H J; Engels, Rutger C M E; Prinstein, Mitchell J; Wiers, Reinout W

2012-03-01

The aim of the present study was to examine whether explicit and implicit self-esteem, the interaction between these two constructs, and their discrepancy are associated with depressive symptoms, suicidal ideation, and loneliness. Participants were 95 young female adults (M = 21.2 years, SD = 1.88) enrolled in higher education. We administered the Name Letter Task to measure implicit self-esteem, and the Rosenberg self-esteem scale to assess explicit self-esteem. The results indicated that explicit but not implicit self-esteem was negatively associated with depressive symptoms, suicidal ideation, and loneliness. The interaction of implicit and explicit self-esteem was associated with suicidal ideation, indicating that participants with high implicit self-esteem combined with a low explicit self-esteem showed more suicidal ideation. Furthermore, the size of the discrepancy between implicit and explicit self-esteem was positively associated with depressive symptoms, suicidal ideation, and loneliness. In addition, results showed that the direction of the discrepancy is an important: damaged self-esteem (high implicit self-esteem combined with low explicit self-esteem) was consistently associated with increased levels of depressive symptoms, suicidal ideation, and loneliness, while defensive or fragile self-esteem (high explicit and low implicit self-esteem) was not. Together, these findings provide new insights into the relationship of implicit and explicit self-esteem with depressive symptoms, suicidal ideation, and loneliness. Copyright © 2011 Elsevier Ltd. All rights reserved.

"Whether I like it or not, it's important": Implicit importance of means predicts self-regulatory persistence and success.

PubMed

Critcher, Clayton R; Ferguson, Melissa J

2016-06-01

To effectively self-regulate, people must persevere on tasks that they deem important, regardless of whether those tasks are enjoyable. Building on past work that has noted the fundamental role of implicit cognition in guiding effective self-regulation, the present paper tests whether an implicit association between goal means and importance predicts self-regulatory persistence and success. Implicit importance predicted markers of effective self-regulation-better grades, more studying and exercise, and stronger standardized testing performance-over and above, and often better than, explicit beliefs about the importance of that self-regulation, as well as implicit evaluations of those means. In particular, those for whom tasks were fairly taxing to complete (i.e., those for whom this self-regulation required effortful self-control) were those who most benefitted from the implicit association between means and importance. Moreover, when participants were reminded of recent self-regulatory failure that they believed could be overcome through hard work, implicit importance toward the means increased as if to prepare them to achieve self-regulatory persistence. A final study sought to reconcile the present findings with previous work showing the key role that implicit evaluations play in effective self-regulation. We reasoned that means are important precisely because they are associated with valued end-states. Consistent with this account, implicit evaluations of end-states predicted the implicit importance of means, which in turn predicted effective self-regulation. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Effects of pretesting implicit self-determined motivation on behavioral engagement: evidence for the mere measurement effect at the implicit level.

PubMed

Keatley, David A; Clarke, David D; Ferguson, Eamonn; Hagger, Martin S

2014-01-01

Research into individuals' intended behavior and performance has traditionally adopted explicitly measured, self-report constructs, and outcomes. More recently, research has shown that completing explicit self-report measures of constructs may effect subsequent behavior, termed the "mere measurement" effect. The aim of the present experiment was to investigate whether implicit measures of motivation showed a similar mere measurement effect on subsequent behavior. It may be the case that measuring the implicit systems affects subsequent implicit interventions (e.g., priming), observable on subsequent behavior. Priming manipulations were also given to participants in order to investigate the interaction between measurement and priming of motivation. Initially, a 2 [implicit association test (IAT: present vs. absent) ×2 (Prime: autonomous vs. absent) and a 2 (IAT: present vs. absent) × 2 (Prime: controlled vs. absent)] between participants designs were conducted, these were them combined into a 2 (IAT: present vs. absent) ×3 (Prime: autonomous vs. controlled vs. absent) between participants design, with attempts at a novel task taken as the outcome measure. Implicit measure completion significantly decreased behavioral engagement. Priming autonomous motivation significantly facilitated, and controlled motivation significantly inhibited performance. Finally, there was a significant implicit measurement × priming interaction, such that priming autonomous motivation only improved performance in the absence of the implicit measure. Overall, this research provides an insight into the effects of implicit measurement and priming of motivation and the combined effect of completing both tasks on behavior.

A specific implicit sequence learning deficit as an underlying cause of dyslexia? Investigating the role of attention in implicit learning tasks.

PubMed

Staels, Eva; Van den Broeck, Wim

2017-05-01

Recently, a general implicit sequence learning deficit was proposed as an underlying cause of dyslexia. This new hypothesis was investigated in the present study by including a number of methodological improvements, for example, the inclusion of appropriate control conditions. The second goal of the study was to explore the role of attentional functioning in implicit and explicit learning tasks. In a 2 × 2 within-subjects design 4 tasks were administered in 30 dyslexic and 38 control children: an implicit and explicit serial reaction time (RT) task and an implicit and explicit contextual cueing task. Attentional functioning was also administered. The entire learning curves of all tasks were analyzed using latent growth curve modeling in order to compare performances between groups and to examine the role of attentional functioning on the learning curves. The amount of implicit learning was similar for both groups. However, the dyslexic group showed slower RTs throughout the entire task. This group difference reduced and became nonsignificant after controlling for attentional functioning. Both implicit learning tasks, but none of the explicit learning tasks, were significantly affected by attentional functioning. Dyslexic children do not suffer from a specific implicit sequence learning deficit. The slower RTs of the dyslexic children throughout the entire implicit sequence learning process are caused by their comorbid attention problems and overall slowness. A key finding of the present study is that, in contrast to what was assumed for a long time, implicit learning relies on attentional resources, perhaps even more than explicit learning does. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

The Effects of Oncologist Implicit Racial Bias in Racially Discordant Oncology Interactions

PubMed Central

Dovidio, John F.; Gonzalez, Richard; Albrecht, Terrance L.; Chapman, Robert; Foster, Tanina; Harper, Felicity W.K.; Hagiwara, Nao; Hamel, Lauren M.; Shields, Anthony F.; Gadgeel, Shirish; Simon, Michael S.; Griggs, Jennifer J.; Eggly, Susan

2016-01-01

Purpose Health providers’ implicit racial bias negatively affects communication and patient reactions to many medical interactions. However, its effects on racially discordant oncology interactions are largely unknown. Thus, we examined whether oncologist implicit racial bias has similar effects in oncology interactions. We further investigated whether oncologist implicit bias negatively affects patients’ perceptions of recommended treatments (i.e., degree of confidence, expected difficulty). We predicted oncologist implicit bias would negatively affect communication, patient reactions to interactions, and, indirectly, patient perceptions of recommended treatments. Methods Participants were 18 non-black medical oncologists and 112 black patients. Oncologists completed an implicit racial bias measure several weeks before video-recorded treatment discussions with new patients. Observers rated oncologist communication and recorded interaction length of time and amount of time oncologists and patients spoke. Following interactions, patients answered questions about oncologists’ patient-centeredness and difficulty remembering contents of the interaction, distress, trust, and treatment perceptions. Results As predicted, oncologists higher in implicit racial bias had shorter interactions, and patients and observers rated these oncologists’ communication as less patient-centered and supportive. Higher implicit bias also was associated with more patient difficulty remembering contents of the interaction. In addition, oncologist implicit bias indirectly predicted less patient confidence in recommended treatments, and greater perceived difficulty completing them, through its impact on oncologists’ communication (as rated by both patients and observers). Conclusion Oncologist implicit racial bias is negatively associated with oncologist communication, patients’ reactions to racially discordant oncology interactions, and patient perceptions of recommended treatments. These perceptions could subsequently directly affect patient-treatment decisions. Thus, implicit racial bias is a likely source of racial treatment disparities and must be addressed in oncology training and practice. PMID:27325865

Comparison of Physician Implicit Racial Bias Toward Adults Versus Children.

PubMed

Johnson, Tiffani J; Winger, Daniel G; Hickey, Robert W; Switzer, Galen E; Miller, Elizabeth; Nguyen, Margaret B; Saladino, Richard A; Hausmann, Leslie R M

2017-03-01

The general population and most physicians have implicit racial bias against black adults. Pediatricians also have implicit bias against black adults, albeit less than other specialties. There is no published research on the implicit racial attitudes of pediatricians or other physicians toward children. Our objectives were to compare implicit racial bias toward adults versus children among resident physicians working in a pediatric emergency department, and to assess whether bias varied by specialty (pediatrics, emergency medicine, or other), gender, race, age, and year of training. We measured implicit racial bias of residents before a pediatric emergency department shift using the Adult and Child Race Implicit Association Tests (IATs). Generalized linear models compared Adult and Child IAT scores and determined the association of participant demographics with Adult and Child IAT scores. Among 91 residents, we found moderate pro-white/anti-black bias on both the Adult (mean = 0.49, standard deviation = 0.34) and Child Race IAT (mean = 0.55, standard deviation = 0.37). There was no significant difference between Adult and Child Race IAT scores (difference = 0.06, P = .15). Implicit bias was not associated with resident demographic characteristics, including specialty. This is the first study demonstrating that resident physicians have implicit racial bias against black children, similar to levels of bias against black adults. Bias in our study did not vary by resident demographic characteristics, including specialty, suggesting that pediatric residents are as susceptible as other physicians to implicit bias. Future studies are needed to explore how physicians' implicit attitudes toward parents and children may impact inequities in pediatric health care. Copyright © 2016 Academic Pediatric Association. All rights reserved.

The Effects of Oncologist Implicit Racial Bias in Racially Discordant Oncology Interactions.

PubMed

Penner, Louis A; Dovidio, John F; Gonzalez, Richard; Albrecht, Terrance L; Chapman, Robert; Foster, Tanina; Harper, Felicity W K; Hagiwara, Nao; Hamel, Lauren M; Shields, Anthony F; Gadgeel, Shirish; Simon, Michael S; Griggs, Jennifer J; Eggly, Susan

2016-08-20

Health providers' implicit racial bias negatively affects communication and patient reactions to many medical interactions. However, its effects on racially discordant oncology interactions are largely unknown. Thus, we examined whether oncologist implicit racial bias has similar effects in oncology interactions. We further investigated whether oncologist implicit bias negatively affects patients' perceptions of recommended treatments (i.e., degree of confidence, expected difficulty). We predicted oncologist implicit bias would negatively affect communication, patient reactions to interactions, and, indirectly, patient perceptions of recommended treatments. Participants were 18 non-black medical oncologists and 112 black patients. Oncologists completed an implicit racial bias measure several weeks before video-recorded treatment discussions with new patients. Observers rated oncologist communication and recorded interaction length of time and amount of time oncologists and patients spoke. Following interactions, patients answered questions about oncologists' patient-centeredness and difficulty remembering contents of the interaction, distress, trust, and treatment perceptions. As predicted, oncologists higher in implicit racial bias had shorter interactions, and patients and observers rated these oncologists' communication as less patient-centered and supportive. Higher implicit bias also was associated with more patient difficulty remembering contents of the interaction. In addition, oncologist implicit bias indirectly predicted less patient confidence in recommended treatments, and greater perceived difficulty completing them, through its impact on oncologists' communication (as rated by both patients and observers). Oncologist implicit racial bias is negatively associated with oncologist communication, patients' reactions to racially discordant oncology interactions, and patient perceptions of recommended treatments. These perceptions could subsequently directly affect patient-treatment decisions. Thus, implicit racial bias is a likely source of racial treatment disparities and must be addressed in oncology training and practice. © 2016 by American Society of Clinical Oncology.

Face puzzle—two new video-based tasks for measuring explicit and implicit aspects of facial emotion recognition

PubMed Central

Kliemann, Dorit; Rosenblau, Gabriela; Bölte, Sven; Heekeren, Hauke R.; Dziobek, Isabel

2013-01-01

Recognizing others' emotional states is crucial for effective social interaction. While most facial emotion recognition tasks use explicit prompts that trigger consciously controlled processing, emotional faces are almost exclusively processed implicitly in real life. Recent attempts in social cognition suggest a dual process perspective, whereby explicit and implicit processes largely operate independently. However, due to differences in methodology the direct comparison of implicit and explicit social cognition has remained a challenge. Here, we introduce a new tool to comparably measure implicit and explicit processing aspects comprising basic and complex emotions in facial expressions. We developed two video-based tasks with similar answer formats to assess performance in respective facial emotion recognition processes: Face Puzzle, implicit and explicit. To assess the tasks' sensitivity to atypical social cognition and to infer interrelationship patterns between explicit and implicit processes in typical and atypical development, we included healthy adults (NT, n = 24) and adults with autism spectrum disorder (ASD, n = 24). Item analyses yielded good reliability of the new tasks. Group-specific results indicated sensitivity to subtle social impairments in high-functioning ASD. Correlation analyses with established implicit and explicit socio-cognitive measures were further in favor of the tasks' external validity. Between group comparisons provide first hints of differential relations between implicit and explicit aspects of facial emotion recognition processes in healthy compared to ASD participants. In addition, an increased magnitude of between group differences in the implicit task was found for a speed-accuracy composite measure. The new Face Puzzle tool thus provides two new tasks to separately assess explicit and implicit social functioning, for instance, to measure subtle impairments as well as potential improvements due to social cognitive interventions. PMID:23805122

Unconscious Race and Class Biases among Registered Nurses: Vignette-Based Study Using Implicit Association Testing.

PubMed

Haider, Adil H; Schneider, Eric B; Sriram, N; Scott, Valerie K; Swoboda, Sandra M; Zogg, Cheryl K; Dhiman, Nitasha; Haut, Elliott R; Efron, David T; Pronovost, Peter J; Freischlag, Julie A; Lipsett, Pamela A; Cornwell, Edward E; MacKenzie, Ellen J; Cooper, Lisa A

2015-06-01

Implicit bias is an unconscious preference for a specific social group that can have adverse consequences for patient care. Acute care clinical vignettes were used to examine whether implicit race or class biases among registered nurses (RNs) impacted patient-management decisions. In a prospective study conducted among surgical RNs at the Johns Hopkins Hospital, participants were presented 8 multi-stage clinical vignettes in which patients' race or social class were randomly altered. Registered nurses were administered implicit association tests (IATs) for social class and race. Ordered logistic regression was then used to examine associations among treatment differences, race, or social class, and RN's IAT scores. Spearman's rank coefficients comparing RN's implicit (IAT) and explicit (stated) preferences were also investigated. Two hundred and forty-five RNs participated. The majority were female (n=217 [88.5%]) and white (n=203 [82.9%]). Most reported that they had no explicit race or class preferences (n=174 [71.0%] and n=108 [44.1%], respectively). However, only 36 nurses (14.7%) demonstrated no implicit race preference as measured by race IAT, and only 16 nurses (6.53%) displayed no implicit class preference on the class IAT. Implicit association tests scores did not statistically correlate with vignette-based clinical decision making. Spearman's rank coefficients comparing implicit (IAT) and explicit preferences also demonstrated no statistically significant correlation (r=-0.06; p=0.340 and r=-0.06; p=0.342, respectively). The majority of RNs displayed implicit preferences toward white race and upper social class patients on IAT assessment. However, unlike published data on physicians, implicit biases among RNs did not correlate with clinical decision making. Copyright © 2015 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Co-occurrence of social anxiety and depression symptoms in adolescence: differential links with implicit and explicit self-esteem?

PubMed

de Jong, P J; Sportel, B E; de Hullu, E; Nauta, M H

2012-03-01

Social anxiety and depression often co-occur. As low self-esteem has been identified as a risk factor for both types of symptoms, it may help to explain their co-morbidity. Current dual process models of psychopathology differentiate between explicit and implicit self-esteem. Explicit self-esteem would reflect deliberate self-evaluative processes whereas implicit self-esteem would reflect simple associations in memory. Previous research suggests that low explicit self-esteem is involved in both social anxiety and depression whereas low implicit self-esteem is only involved in social anxiety. We tested whether the association between symptoms of social phobia and depression can indeed be explained by low explicit self-esteem, whereas low implicit self-esteem is only involved in social anxiety. Adolescents during the first stage of secondary education (n=1806) completed the Revised Child Anxiety and Depression Scale (RCADS) to measure symptoms of social anxiety and depression, the Rosenberg Self-Esteem Scale (RSES) to index explicit self-esteem and the Implicit Association Test (IAT) to measure implicit self-esteem. There was a strong association between symptoms of depression and social anxiety that could be largely explained by participants' explicit self-esteem. Only for girls did implicit self-esteem and the interaction between implicit and explicit self-esteem show small cumulative predictive validity for social anxiety, indicating that the association between low implicit self-esteem and social anxiety was most evident for girls with relatively low explicit self-esteem. Implicit self-esteem showed no significant predictive validity for depressive symptoms. The findings support the view that both shared and differential self-evaluative processes are involved in depression and social anxiety.

Implicit Social Cognitive Processes Underlying Victim Self and Identity: Evidence With College-Aged Adults.

PubMed

Sachs, Nicole M; Veysey, Bonita M; Rivera, Luis M

2017-11-01

Past research on victimization has relied predominantly on individuals' awareness of and willingness to self-report a victimization experience and its effect on self and identity processes. The present research adopts theoretical and methodological innovations in implicit social cognition research to provide a new perspective on how a violent victimization experience might influence identity processes outside of conscious awareness. Our main goal was to test whether individuals who have victimization experience implicitly associate the self with victims (implicit victim identity) and their stereotypes (implicit victim self-stereotyping), and the relation of these associations to explicit victim identity and self-stereotyping. Two pretests with undergraduate student participants ( Ns = 122 and 72) identified victim-related word stimuli for two Single Category Implicit Association Test (SC-IAT) measures of implicit victim identity and self-stereotyping. In Pretest Study A, participants read crime vignettes and listed words that described a victim, then in Pretest Study B, participants rated these words on victim relatedness and valence. The Main Study recruited undergraduate student participants ( N = 101) who completed the SC-IATs, self-report measures of explicit victim identity and self-stereotyping, and victimization experiences. Three of our five hypotheses were supported. Individuals with past victimization experience exhibited strong explicit victim identity and self-stereotyping, but not implicit victim identity and self-stereotyping, relative to those with no victimization experience. Explicit and implicit victim identity and self-stereotyping were unrelated. Finally, among individuals with victimization experience, a strong implicit victim identity was associated with strong implicit victim self-stereotyping. This research has implications for understanding the processes underlying revictimization and for preventing further victimization.

Long Term Memory for Noise: Evidence of Robust Encoding of Very Short Temporal Acoustic Patterns.

PubMed

Viswanathan, Jayalakshmi; Rémy, Florence; Bacon-Macé, Nadège; Thorpe, Simon J

2016-01-01

Recent research has demonstrated that humans are able to implicitly encode and retain repeating patterns in meaningless auditory noise. Our study aimed at testing the robustness of long-term implicit recognition memory for these learned patterns. Participants performed a cyclic/non-cyclic discrimination task, during which they were presented with either 1-s cyclic noises (CNs) (the two halves of the noise were identical) or 1-s plain random noises (Ns). Among CNs and Ns presented once, target CNs were implicitly presented multiple times within a block, and implicit recognition of these target CNs was tested 4 weeks later using a similar cyclic/non-cyclic discrimination task. Furthermore, robustness of implicit recognition memory was tested by presenting participants with looped (shifting the origin) and scrambled (chopping sounds into 10- and 20-ms bits before shuffling) versions of the target CNs. We found that participants had robust implicit recognition memory for learned noise patterns after 4 weeks, right from the first presentation. Additionally, this memory was remarkably resistant to acoustic transformations, such as looping and scrambling of the sounds. Finally, implicit recognition of sounds was dependent on participant's discrimination performance during learning. Our findings suggest that meaningless temporal features as short as 10 ms can be implicitly stored in long-term auditory memory. Moreover, successful encoding and storage of such fine features may vary between participants, possibly depending on individual attention and auditory discrimination abilities. Significance Statement Meaningless auditory patterns could be implicitly encoded and stored in long-term memory.Acoustic transformations of learned meaningless patterns could be implicitly recognized after 4 weeks.Implicit long-term memories can be formed for meaningless auditory features as short as 10 ms.Successful encoding and long-term implicit recognition of meaningless patterns may strongly depend on individual attention and auditory discrimination abilities.

Long Term Memory for Noise: Evidence of Robust Encoding of Very Short Temporal Acoustic Patterns

PubMed Central

Viswanathan, Jayalakshmi; Rémy, Florence; Bacon-Macé, Nadège; Thorpe, Simon J.

2016-01-01

Recent research has demonstrated that humans are able to implicitly encode and retain repeating patterns in meaningless auditory noise. Our study aimed at testing the robustness of long-term implicit recognition memory for these learned patterns. Participants performed a cyclic/non-cyclic discrimination task, during which they were presented with either 1-s cyclic noises (CNs) (the two halves of the noise were identical) or 1-s plain random noises (Ns). Among CNs and Ns presented once, target CNs were implicitly presented multiple times within a block, and implicit recognition of these target CNs was tested 4 weeks later using a similar cyclic/non-cyclic discrimination task. Furthermore, robustness of implicit recognition memory was tested by presenting participants with looped (shifting the origin) and scrambled (chopping sounds into 10− and 20-ms bits before shuffling) versions of the target CNs. We found that participants had robust implicit recognition memory for learned noise patterns after 4 weeks, right from the first presentation. Additionally, this memory was remarkably resistant to acoustic transformations, such as looping and scrambling of the sounds. Finally, implicit recognition of sounds was dependent on participant's discrimination performance during learning. Our findings suggest that meaningless temporal features as short as 10 ms can be implicitly stored in long-term auditory memory. Moreover, successful encoding and storage of such fine features may vary between participants, possibly depending on individual attention and auditory discrimination abilities. Significance Statement Meaningless auditory patterns could be implicitly encoded and stored in long-term memory.Acoustic transformations of learned meaningless patterns could be implicitly recognized after 4 weeks.Implicit long-term memories can be formed for meaningless auditory features as short as 10 ms.Successful encoding and long-term implicit recognition of meaningless patterns may strongly depend on individual attention and auditory discrimination abilities. PMID:27932941

Binding of Estrogenic Compounds to Recombinant Estrogen Receptor-α: Application to Environmental Analysis

PubMed Central

Pillon, Arnaud; Boussioux, Anne-Marie; Escande, Aurélie; Aït-Aïssa, Sélim; Gomez, Elena; Fenet, Hélène; Ruff, Marc; Moras, Dino; Vignon, Françoise; Duchesne, Marie-Josèphe; Casellas, Claude; Nicolas, Jean-Claude; Balaguer, Patrick

2005-01-01

Estrogenic activity in environmental samples could be mediated through a wide variety of compounds and by various mechanisms. High-affinity compounds for estrogen receptors (ERs), such as natural or synthetic estrogens, as well as low-affinity compounds such as alkylphenols, phthalates, and polychlorinated biphenyls are present in water and sediment samples. Furthermore, compounds such as polycyclic aromatic hydrocarbons, which do not bind ERs, modulate estrogen activity by means of the aryl hydrocarbon receptor (AhR). In order to characterize compounds that mediate estrogenic activity in river water and sediment samples, we developed a tool based on the ER-αligand-binding domain, which permitted us to estimate contaminating estrogenic compound affinities. We designed a simple transactivation assay in which compounds of high affinity were captured by limited amounts of recombinant ER-αand whose capture led to a selective inhibition of transactivation. This approach allowed us to bring to light that water samples contain estrogenic compounds that display a high affinity for ERs but are present at low concentrations. In sediment samples, on the contrary, we showed that estrogenic compounds possess a low affinity and are present at high concentration. Finally, we used immobilized recombinant ER-αto separate ligands for ER and AhR that are present in river sediments. Immobilized ER-α, which does not retain dioxin-like compounds, enabled us to isolate and concentrate ER ligands to facilitate their further analysis. PMID:15743715

Implicit and explicit self-esteem discrepancies in people with psychogenic nonepileptic seizures.

PubMed

Dimaro, Lian V; Roberts, Nicole A; Moghaddam, Nima G; Dawson, David L; Brown, Ian; Reuber, Markus

2015-05-01

Self-esteem (SE), or one's sense of competence and worth, is reduced in many mental and physical disorders. Low SE is associated with perceived stigma and disability and poor treatment outcomes. The present study examined implicit and explicit SE (automatic and deliberate views about the self) in people with epilepsy and people with psychogenic nonepileptic seizures (PNESs). Discrepancies between implicit SE and explicit SE have been found to correlate with psychological distress in disorders often associated with PNESs but are relatively unexplored in PNESs. We hypothesized that, compared with epilepsy, PNESs would be associated with lower self-reported SE and greater discrepancies between implicit SE and explicit SE. Thirty adults with PNESs, 25 adults with epilepsy, and 31 controls without a history of seizures were asked to complete the Rosenberg Self-esteem Scale as a measure of explicit SE and an Implicit Relational Assessment Procedure as a measure of implicit SE. The State-Trait Anxiety Inventory and Patient Health Questionnaire-15 (a somatic symptom inventory) were also administered. We found significant group differences in explicit (p<0.001) but not implicit SE. Patients with PNESs reported lower SE than the other groups. No group differences were found in implicit SE. Implicit-explicit SE discrepancies were larger in the group with PNESs than in the other groups (p<0.001). Higher frequency of PNESs (but not epileptic seizures) was associated with lower explicit SE (rs=-.83, p<0.01) and greater SE discrepancies (i.e., lower explicit relative to implicit SE; rs=.65, p<0.01). These relationships remained significant when controlling for anxiety and somatization. Patients with PNESs had lower explicit SE than those with epilepsy or healthy controls. In keeping with our expectations, there were greater discrepancies between implicit SE and explicit SE among patients with PNESs than in the other groups. Our results, including the strong relationship between PNES frequency, anxiety, and explicit-implicit SE discrepancies, support the interpretation that PNESs serve to reduce cognitive dissonance, perhaps protecting patients' implicit SE. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

Ligand migration in the truncated hemoglobin of Mycobacterium tuberculosis.

PubMed

Heroux, Maxime S; Mohan, Anne D; Olsen, Kenneth W

2011-03-01

The truncated hemoglobin of Mycobacterium tuberculosis (Mt-trHbO) is a small heme protein belonging to the hemoglobin superfamily. Truncated hemoglobins (trHbs) are believed to have functional roles such as terminal oxidases and oxygen sensors involved in the response to oxidative and nitrosative stress, nitric oxide (NO) detoxification, O₂/NO chemistry, O₂ delivery under hypoxic conditions, and long-term ligand storage. Based on sequence similarities, they are classified into three groups. Experimental studies revealed that all trHbs display a 2-on-2 α-helical sandwich fold rather than the 3-on-3 α-helical sandwich fold of the classical hemoglobin fold. Using locally enhanced sampling (LESMD) molecular dynamics, the ligand-binding escape pathways from the distal heme binding cavity of Mt-trHbO were determined to better understand how this protein functions. The importance of specific residues, such as the group II and III invariant W(G8) residue, can be seen in terms of ligand diffusion pathways and ligand dynamics. LESMD simulations show that the wild-type Mt-trHbO has three diffusion pathways while the W(G8)F Mt-trHbO mutant has only two. The W(G8) residue plays a critical role in ligand binding and stabilization and helps regulate the rate of ligand escape from the distal heme pocket. Thus, this invariant residue is important in creating ligand diffusion pathways and possibly in the enzymatic functions of this protein. Copyright © 2011 Wiley Periodicals, Inc.

Preparation of a functional fluorescent human Fas ligand extracellular domain derivative using a three-dimensional structure guided site-specific fluorochrome conjugation.

PubMed

Muraki, Michiro

2016-01-01

Human Fas ligand extracellular domain has been investigated as an important target protein in the field of medical biotechnology. In a recent study, the author developed an effective method to produce biologically active human Fas ligand extracellular domain derivatives using site-specific chemical modifications. A human Fas ligand extracellular domain derivative containing a reactive cysteine residue within its N-terminal tag sequence, which locates not proximal to the binding interface between the ligand and the receptor in terms of the three-dimensional structure, was modified by Fluorescein-5-Maleimide without impairing the specific binding activity toward human Fas receptor extracellular domain. The purified protein sample free of low molecular-weight contaminants showed a characteristic fluorescence spectrum derived from the attached Fluorescein moieties, and formed a stable binding complex with human Fas receptor extracellular domain-human IgG1 Fc domain fusion protein in solution. The conjugation number of the fluorochrome was estimated to be 2.5 per a single human Fas ligand extracellular domain trimer from the ratio of the absorbance value at 280 nm to that at 495 nm. A functional fluorescent human Fas ligand extracellular domain derivative was prepared via a site-specific conjugation of fluorochrome, which was guided by the three-dimensional structure information on the ligand-receptor complex. Fluorescent derivatives created by this method may contribute to the development of an improved diagnosis system for the diseases related to Fas receptor.

A generic template for automated bioanalytical ligand-binding assays using modular robotic scripts in support of discovery biotherapeutic programs.

PubMed

Duo, Jia; Dong, Huijin; DeSilva, Binodh; Zhang, Yan J

2013-07-01

Sample dilution and reagent pipetting are time-consuming steps in ligand-binding assays (LBAs). Traditional automation-assisted LBAs use assay-specific scripts that require labor-intensive script writing and user training. Five major script modules were developed on Tecan Freedom EVO liquid handling software to facilitate the automated sample preparation and LBA procedure: sample dilution, sample minimum required dilution, standard/QC minimum required dilution, standard/QC/sample addition, and reagent addition. The modular design of automation scripts allowed the users to assemble an automated assay with minimal script modification. The application of the template was demonstrated in three LBAs to support discovery biotherapeutic programs. The results demonstrated that the modular scripts provided the flexibility in adapting to various LBA formats and the significant time saving in script writing and scientist training. Data generated by the automated process were comparable to those by manual process while the bioanalytical productivity was significantly improved using the modular robotic scripts.

Mainstream Teachers' Implicit Beliefs about English Language Learners: An Implicit Association Test Study of Teacher Beliefs

ERIC Educational Resources Information Center

Harrison, Jamie; Lakin, Joni

2018-01-01

Teacher attitudes toward inclusion of English Learners (ELs) in the mainstream classroom have primarily focused on explicit beliefs as accessed through observation, case studies, and self-report surveys. The authors explore implicit mainstream teacher beliefs about ELs using the newly created Implicit Association Test-EL, with correlations to…

A Review of Experimental Studies of Explicit and Implicit Bias among Counselors

ERIC Educational Resources Information Center

Boysen, Guy A.

2009-01-01

Bias is a central concept in multicultural competency, but counseling research has largely ignored implicit bias. A review of bias research in counseling indicates that increased focus on implicit bias is warranted because counselors tend not to report explicit bias and have implicit bias that diverges from their self-reported attitudes. (Contains…

The Implicit Relational Assessment Procedure (IRAP) as a Measure of Implicit Relative Preferences: A First Study

ERIC Educational Resources Information Center

Power, Patricia; Barnes-Holmes, Dermot; Barnes-Holmes, Yvonne; Stewart, Ian

2009-01-01

The Implicit Relational Assessment Procedure (IRAP) was designed to examine implicit beliefs or attitudes. In Experiment 1, response latencies obtained from Irish participants on the IRAP showed a strong preference for Irish over Scottish and American over African. In contrast, responses to explicit Likert measures diverged from the IRAP…

Corrective Feedback and Second Language Acquisition: Differential Contributions of Implicit and Explicit Knowledge

ERIC Educational Resources Information Center

Ebadi, Mandana Rohollahzadeh; Saad, Mohd Rashid Mohd; Abedalaziz, Nabil

2014-01-01

The issue of error correction remains controversial in recent years due to the different positions of interface toward implicit and explicit knowledge of ESL learners. This study looks at the impacts of implicit corrective feedback in the form of recast on implicit and explicit knowledge of adult ESL learners. In an experimental study,…

From American City to Japanese Village: A Cross-Cultural Investigation of Implicit Race Attitudes

ERIC Educational Resources Information Center

Dunham, Yarrow; Baron, Andrew Scott; Banaji, Mahzarin R.

2006-01-01

This study examined the development of implicit race attitudes in American and Japanese children and adults. Implicit ingroup bias was present early in both populations, and remained stable at each age tested (age 6, 10, and adult). Similarity in magnitude and developmental course across these 2 populations suggests that implicit intergroup bias…

Using the implicit relational assessment procedure to compare implicit pro-thin/anti-fat attitudes of patients with anorexia nervosa and non-clinical controls.

PubMed

Parling, Thomas; Cernvall, Martin; Stewart, Ian; Barnes-Holmes, Dermot; Ghaderi, Ata

2012-01-01

Implicit pro-thin/anti-fat attitudes were investigated among a mixed group of patients with full and sub-threshold Anorexia Nervosa (n = 17), and a matched-age control group (n = 17). The Implicit Relational Assessment Procedure (IRAP) was employed to measure implicit pro-thin and anti-fat attitudes towards Self and Others in addition to "striving for thinness" and "avoidance of fatness." The clinical group showed an implicit pro-fat attitude towards Others and stronger anti-fat attitudes towards Self and avoidance of fatness compared with controls. The findings are discussed in relation to the over-evaluation of weight and shape in the clinical group.

The time course of explicit and implicit categorization.

PubMed

Smith, J David; Zakrzewski, Alexandria C; Herberger, Eric R; Boomer, Joseph; Roeder, Jessica L; Ashby, F Gregory; Church, Barbara A

2015-10-01

Contemporary theory in cognitive neuroscience distinguishes, among the processes and utilities that serve categorization, explicit and implicit systems of category learning that learn, respectively, category rules by active hypothesis testing or adaptive behaviors by association and reinforcement. Little is known about the time course of categorization within these systems. Accordingly, the present experiments contrasted tasks that fostered explicit categorization (because they had a one-dimensional, rule-based solution) or implicit categorization (because they had a two-dimensional, information-integration solution). In Experiment 1, participants learned categories under unspeeded or speeded conditions. In Experiment 2, they applied previously trained category knowledge under unspeeded or speeded conditions. Speeded conditions selectively impaired implicit category learning and implicit mature categorization. These results illuminate the processing dynamics of explicit/implicit categorization.

The nature of declarative and nondeclarative knowledge for implicit and explicit learning.

PubMed

Kirkhart, M W

2001-10-01

Using traditional implicit and explicit artificial-grammar learning tasks, the author investigated the similarities and differences between the acquisition of declarative knowledge under implicit and explicit learning conditions and the functions of the declarative knowledge during testing. Results suggested that declarative knowledge was not predictive of or required for implicit learning but was related to consistency in implicit learning performance. In contrast, declarative knowledge was predictive of and required for explicit learning and was related to consistency in performance. For explicit learning, the declarative knowledge functioned as a guide for other behavior. In contrast, for implicit learning, the declarative knowledge did not serve as a guide for behavior but was instead a post hoc description of the most commonly seen stimuli.

Implicit Kalman filtering

NASA Technical Reports Server (NTRS)

Skliar, M.; Ramirez, W. F.

1997-01-01

For an implicitly defined discrete system, a new algorithm for Kalman filtering is developed and an efficient numerical implementation scheme is proposed. Unlike the traditional explicit approach, the implicit filter can be readily applied to ill-conditioned systems and allows for generalization to descriptor systems. The implementation of the implicit filter depends on the solution of the congruence matrix equation (A1)(Px)(AT1) = Py. We develop a general iterative method for the solution of this equation, and prove necessary and sufficient conditions for convergence. It is shown that when the system matrices of an implicit system are sparse, the implicit Kalman filter requires significantly less computer time and storage to implement as compared to the traditional explicit Kalman filter. Simulation results are presented to illustrate and substantiate the theoretical developments.

Adaptive Biasing Combined with Hamiltonian Replica Exchange to Improve Umbrella Sampling Free Energy Simulations.

PubMed

Zeller, Fabian; Zacharias, Martin

2014-02-11

The accurate calculation of potentials of mean force for ligand-receptor binding is one of the most important applications of molecular simulation techniques. Typically, the separation distance between ligand and receptor is chosen as a reaction coordinate along which a PMF can be calculated with the aid of umbrella sampling (US) techniques. In addition, restraints can be applied on the relative position and orientation of the partner molecules to reduce accessible phase space. An approach combining such phase space reduction with flattening of the free energy landscape and configurational exchanges has been developed, which significantly improves the convergence of PMF calculations in comparison with standard umbrella sampling. The free energy surface along the reaction coordinate is smoothened by iteratively adapting biasing potentials corresponding to previously calculated PMFs. Configurations are allowed to exchange between the umbrella simulation windows via the Hamiltonian replica exchange method. The application to a DNA molecule in complex with a minor groove binding ligand indicates significantly improved convergence and complete reversibility of the sampling along the pathway. The calculated binding free energy is in excellent agreement with experimental results. In contrast, the application of standard US resulted in large differences between PMFs calculated for association and dissociation pathways. The approach could be a useful alternative to standard US for computational studies on biomolecular recognition processes.

A machine learning approach to predicting protein-ligand binding affinity with applications to molecular docking.

PubMed

Ballester, Pedro J; Mitchell, John B O

2010-05-01

Accurately predicting the binding affinities of large sets of diverse protein-ligand complexes is an extremely challenging task. The scoring functions that attempt such computational prediction are essential for analysing the outputs of molecular docking, which in turn is an important technique for drug discovery, chemical biology and structural biology. Each scoring function assumes a predetermined theory-inspired functional form for the relationship between the variables that characterize the complex, which also include parameters fitted to experimental or simulation data and its predicted binding affinity. The inherent problem of this rigid approach is that it leads to poor predictivity for those complexes that do not conform to the modelling assumptions. Moreover, resampling strategies, such as cross-validation or bootstrapping, are still not systematically used to guard against the overfitting of calibration data in parameter estimation for scoring functions. We propose a novel scoring function (RF-Score) that circumvents the need for problematic modelling assumptions via non-parametric machine learning. In particular, Random Forest was used to implicitly capture binding effects that are hard to model explicitly. RF-Score is compared with the state of the art on the demanding PDBbind benchmark. Results show that RF-Score is a very competitive scoring function. Importantly, RF-Score's performance was shown to improve dramatically with training set size and hence the future availability of more high-quality structural and interaction data is expected to lead to improved versions of RF-Score. pedro.ballester@ebi.ac.uk; jbom@st-andrews.ac.uk Supplementary data are available at Bioinformatics online.

Why dissolved organic matter (DOM) enhances photodegradation of methylmercury

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qian, Yun; Yin, Xiangping Lisa; Brooks, Scott C

2014-01-01

Methylmercury (MeHg) is known to degrade photochemically, but it remains unclear what roles naturally dissolved organic matter (DOM) and complexing organic ligands play in MeHg photodegradation. Here we investigate the rates and mechanisms of MeHg photodegradation using DOM samples with varying oxidation states and origins as well as organic ligands with known molecular structures. All DOM and organic ligands increased MeHg photodegradation under solar irradiation, but the first-order rate constants varied depending on the oxidation state of DOM and the type and concentration of the ligands. Compounds containing both thiols and aromatics (e.g., thiosalicylate and reduced DOM) increased MeHg degradationmore » rates far greater than those containing only aromatic or thiol functional groups (e.g., salicylate or glutathione). Our results suggest that, among other factors, the synergistic effects of thiolate and aromatic moieties in DOM greatly enhance MeHg photodegradation.« less

Conformational free energy modeling of druglike molecules by metadynamics in the WHIM space.

PubMed

Spiwok, Vojtěch; Hlat-Glembová, Katarína; Tvaroška, Igor; Králová, Blanka

2012-03-26

Protein-ligand affinities can be significantly influenced not only by the interaction itself but also by conformational equilibrium of both binding partners, free ligand and free protein. Identification of important conformational families of a ligand and prediction of their thermodynamics is important for efficient ligand design. Here we report conformational free energy modeling of nine small-molecule drugs in explicitly modeled water by metadynamics with a bias potential applied in the space of weighted holistic invariant molecular (WHIM) descriptors. Application of metadynamics enhances conformational sampling compared to unbiased molecular dynamics simulation and allows to predict relative free energies of key conformations. Selected free energy minima and one example of transition state were tested by a series of unbiased molecular dynamics simulation. Comparison of free energy surfaces of free and target-bound Imatinib provides an estimate of free energy penalty of conformational change induced by its binding to the target. © 2012 American Chemical Society

Pd-bound functionalized mesoporous silica as active catalyst for Suzuki coupling reaction: Effect of OAcˉ, PPh3 and Clˉ ligands on catalytic activity

NASA Astrophysics Data System (ADS)

Das, Trisha; Uyama, Hiroshi; Nandi, Mahasweta

2018-04-01

Three new palladium catalysts, PdCat-I, PdCat-II and PdCat-III, immobilized over heterogeneous silica support have been synthesized using different ligands attached to the palladium precursor. The ligands that have been used in this study are acetate, triphenylphosphine and chloride in PdCat-I, PdCat-II and PdCat-III, respectively. The ligands have different effect on stability of the compounds and impart different oxidation states to the metal center. The materials have been characterized by powder X-ray diffraction, nitrogen adsorption-desorption studies, transmission electron microscopy, thermal analysis, and different spectroscopic techniques. The Pd-content of the samples have been determined by ICP-AES analysis. The materials have been used as catalysts for Suzuki coupling reaction of aryl halides with phenylboronic acid under mild conditions. A comparative study has been carried out to ascertain the effect of the nature of different ligands on the outcome of the catalytic reactions. Products have been identified and estimated by 1H NMR and gas chromatography. The results show that the best yields are obtained with the catalyst containing triphenylphosphine as the ligand in methanol. Such type of work to study the effect of ligand on Suzuki coupling reaction over functionalized mesoporous silica heterogeneous catalysts have not been carried out so far.

Investigation of the weak binding of a tetrahistidine-tagged peptide to quantum dots by using capillary electrophoresis with fluorescence detection.

PubMed

Qin, Haifang; Jiang, Xiyuan; Fan, Jie; Wang, Jianpeng; Liu, Li; Qiu, Lin; Wang, Jianhao; Jiang, Pengju

2017-01-01

Capillary electrophoresis with fluorescence detection was utilized to probe the self-assembly between cyanine group dye labeled tetrahistidine containing peptide and CdSe/ZnS quantum dots, inside the capillary. Quantum dots and cyanine group dye labeled tetrahistidine containing peptide were injected into the capillary one after the other and allowed to self-assemble. Their self-assembly resulted into a measurable Förster resonance energy transfer signal between quantum dots and cyanine group dye labeled tetrahistidine containing peptide. The Förster resonance energy transfer signal increased upon increasing the cyanine group dye labeled tetrahistidine containing peptide/quantum dot molar ratio and reached a plateau at the 32/1 molar ratio. Additionally, the Förster resonance energy transfer signal was also affected by the increment of the interval time of injection and the sampling time. Online ligand exchange experiments were used to assess, the potential of a monovalent ligand of imidazole and a hexavalent ligand peptide, to displace surface bound cyanine group dye labeled peptide ligands from the quantum dots surface. Under optimal conditions, a linear relationship between the integrated peak areas and hexavalent ligand peptide was obtained at a hexavalent ligand concentration range of 0-0.5 mM. Therefore, the present assay has the potential to be applied in the online ligands detection. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Applying the Quadruple Process Model to Evaluate Change in Implicit Attitudinal Responses During Therapy for Panic Disorder

PubMed Central

Clerkin, Elise M.; Fisher, Christopher R.; Sherman, Jeffrey W.; Teachman, Bethany A.

2013-01-01

Objective This study explored the automatic and controlled processes that may influence performance on an implicit measure across cognitive-behavioral group therapy for panic disorder. Method The Quadruple Process model was applied to error scores from an Implicit Association Test evaluating associations between the concepts Me (vs. Not Me) + Calm (vs. Panicked) to evaluate four distinct processes: Association Activation, Detection, Guessing, and Overcoming Bias. Parameter estimates were calculated in the panic group (n=28) across each treatment session where the IAT was administered, and at matched times when the IAT was completed in the healthy control group (n=31). Results Association Activation for Me + Calm became stronger over treatment for participants in the panic group, demonstrating that it is possible to change automatically activated associations in memory (vs. simply overriding those associations) in a clinical sample via therapy. As well, the Guessing bias toward the calm category increased over treatment for participants in the panic group. Conclusions This research evaluates key tenets about the role of automatic processing in cognitive models of anxiety, and emphasizes the viability of changing the actual activation of automatic associations in the context of treatment, versus only changing a person’s ability to use reflective processing to overcome biased automatic processing. PMID:24275066

Electro-cortical implicit race bias does not vary with participants’ race or sex

PubMed Central

Mallan, Kimberley M.; Martin, Frances H.; Terry, Deborah J.; Smith, Joanne R.

2011-01-01

Earlier research found evidence for electro-cortical race bias towards black target faces in white American participants irrespective of the task relevance of race. The present study investigated whether an implicit race bias generalizes across cultural contexts and racial in- and out-groups. An Australian sample of 56 Chinese and Caucasian males and females completed four oddball tasks that required sex judgements for pictures of male and female Chinese and Caucasian posers. The nature of the background (across task) and of the deviant stimuli (within task) was fully counterbalanced. Event-related potentials (ERPs) to deviant stimuli recorded from three midline sites were quantified in terms of mean amplitude for four components: N1, P2, N2 and a late positive complex (LPC; 350–700 ms). Deviants that differed from the backgrounds in sex or race elicited enhanced LPC activity. These differences were not modulated by participant race or sex. The current results replicate earlier reports of effects of poser race relative to background race on the LPC component of the ERP waveform. In addition, they indicate that an implicit race bias occurs regardless of participant’s or poser’s race and is not confined to a particular cultural context. PMID:21097957

Sampling and energy evaluation challenges in ligand binding protein design

PubMed Central

Dou, Jiayi; Doyle, Lindsey; Jr. Greisen, Per; Schena, Alberto; Park, Hahnbeom; Johnsson, Kai; Stoddard, Barry L.

2017-01-01

Abstract The steroid hormone 17α‐hydroxylprogesterone (17‐OHP) is a biomarker for congenital adrenal hyperplasia and hence there is considerable interest in development of sensors for this compound. We used computational protein design to generate protein models with binding sites for 17‐OHP containing an extended, nonpolar, shape‐complementary binding pocket for the four‐ring core of the compound, and hydrogen bonding residues at the base of the pocket to interact with carbonyl and hydroxyl groups at the more polar end of the ligand. Eight of 16 designed proteins experimentally tested bind 17‐OHP with micromolar affinity. A co‐crystal structure of one of the designs revealed that 17‐OHP is rotated 180° around a pseudo‐two‐fold axis in the compound and displays multiple binding modes within the pocket, while still interacting with all of the designed residues in the engineered site. Subsequent rounds of mutagenesis and binding selection improved the ligand affinity to nanomolar range, while appearing to constrain the ligand to a single bound conformation that maintains the same “flipped” orientation relative to the original design. We trace the discrepancy in the design calculations to two sources: first, a failure to model subtle backbone changes which alter the distribution of sidechain rotameric states and second, an underestimation of the energetic cost of desolvating the carbonyl and hydroxyl groups of the ligand. The difference between design model and crystal structure thus arises from both sampling limitations and energy function inaccuracies that are exacerbated by the near two‐fold symmetry of the molecule. PMID:28980354

A semisynthetic strategy leads to alteration of the backbone amidate ligand in the NiSOD active site

DOE PAGES

Campeciño, Julius O.; Dudycz, Lech W.; Tumelty, David; ...

2015-07-01

Computational investigations have implicated the amidate ligand in nickel superoxide dismutase (NiSOD) in stabilizing Ni-centered redox catalysis and in preventing cysteine thiolate ligand oxidation. To test these predictions, we have used an experimental approach utilizing a semisynthetic scheme that employs native chemical ligation of a pentapeptide (HCDLP) to recombinant S. coelicolor NiSOD lacking these N-terminal residues, NΔ5-NiSOD. Wild-type enzyme produced in this manner exhibits the characteristic spectral properties of recombinant WT-NiSOD and is as catalytically active. The semisynthetic scheme was also employed to construct a variant where the amidate ligand was converted to a secondary amine, H1*-NiSOD, a novel strategymore » that retains a backbone N-donor atom. The H1*-NiSOD variant was found to have only ~1% of the catalytic activity of the recombinant wild-type enzyme, and had altered spectroscopic properties. X-ray absorption spectroscopy reveals a four-coordinate planar site with N 2S 2-donor ligands, consistent with electronic absorption spectroscopic results indicating that the Ni center in H1*-NiSOD is mostly reduced in the as-isolated sample, as opposed to 50:50 Ni(II)/Ni(III) mixture that is typical for the recombinant wild-type enzyme. The EPR spectrum of as-isolated H1*-NiSOD accounts for ~11% of the Ni in the sample and is similar to WT-NiSOD, but more axial, with g z < g x,y. 14N-hyperfine is observed on g z« less

Macro-level implicit HIV prejudice and the health of community residents with HIV.

PubMed

Miller, Carol T; Varni, Susan E; Solomon, Sondra E; DeSarno, Michael J; Bunn, Janice Y

2016-08-01

This study examined how community levels of implicit HIV prejudice are associated with the psychological and physical well-being of people with HIV living in those same communities. It also examined whether community motivation to control prejudice and/or explicit HIV prejudice moderates the relationship of implicit prejudice and well-being. Participants were 206 people with HIV living in 42 different communities in New England who completed measures that assessed psychological distress, thriving, and physical well-being. Telephone surveys of 347 residents of these same communities (selected via random digit dialing) were used to assess community explicit HIV prejudice and motivation to control HIV prejudice. These community residents then completed an online measure of implicit prejudice toward people with HIV, the Implicit Association Test (IAT; Greenwald, McGhee, & Schwartz, 1998). Multilevel analyses showed that higher community implicit HIV prejudice was associated with greater psychological distress among residents with HIV living in that community. The physical well-being of participants with HIV was negatively related to community implicit HIV prejudice in communities in which residents were unmotivated to control HIV prejudice or had high levels of explicit HIV prejudice. These findings indicate that implicit prejudice of residents of real-world communities may create an environment that may impair the well-being of stigmatized people. Implicit prejudice can therefore be considered an element of macro-level or structural stigma. The discussion considered the possible role of implicit HIV prejudice on a community's social capital as a pathway by which it compromises the well-being of residents with HIV. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Macro-level Implicit HIV Prejudice and the Health of Community Residents with HIV

PubMed Central

Miller, Carol T.; Varni, Susan E.; Solomon, Sondra E.; DeSarno, Michael J.; Bunn, Janice Y.

2016-01-01

Objectives This study examined how community levels of implicit HIV prejudice are associated with the psychological and physical well-being of people with HIV living in those same communities. It also examined whether community motivation to control prejudice and/or explicit HIV prejudice moderates the relationship of implicit prejudice and well-being. Methods Participants were 206 people with HIV living in 42 different communities in New England who completed measures that assessed psychological distress, thriving, and physical well-being. Telephone surveys of 347 residents of these same communities (selected via random digit dialing) were used to assess community explicit HIV prejudice and motivation to control HIV prejudice. These community residents then completed an on-line measure of implicit prejudice toward people with HIV, the Implicit Association Test (IAT, Greenwald et al., 1998). Results Multilevel analyses showed that higher community implicit HIV prejudice was associated with greater psychological distress among residents with HIV living in that community. The physical well-being of participants with HIV was negatively related to community implicit HIV prejudice in communities in which residents were unmotivated to control HIV prejudice or had high levels of explicit HIV prejudice. Conclusions These findings indicate that implicit prejudice of residents of real-world communities may create an environment that may impair the well-being of stigmatized people. Implicit prejudice can therefore be considered an element of macro-level or structural stigma. The discussion considered the possible role of implicit HIV prejudice on a community’s social capital as one pathway by which it compromises the well-being of residents with HIV. PMID:27505199

Discrepancies between explicit and implicit self-esteem and their relationship to symptoms of depression and mania.

PubMed

Pavlickova, Hana; Turnbull, Oliver H; Bentall, Richard P

2014-09-01

Self-esteem is a key feature of bipolar symptomatology. However, so far no study has examined the interaction between explicit and implicit self-esteem in individuals vulnerable to bipolar disorder. Cross-sectional design was employed. Thirty children of parents with bipolar disorder and 30 offspring of control parents completed Hamilton Rating Scale for Depression, the Bech-Rafaelson Mania Scale, the Self-esteem Rating Scale and the Implicit Association Test. No differences between groups were revealed in levels of explicit or implicit self-esteem. However, bipolar offspring showed increased levels of symptoms of depression and mania. Furthermore, depressive symptoms were associated with low explicit self-esteem, whilst symptoms of mania were associated with low implicit self-esteem. When self-esteem discrepancies were examined, damaged self-esteem (i.e., low explicit but high implicit self-esteem) was associated with depression, whilst no associations between mania and self-esteem discrepancies were found. Not only explicit, but also implicit self-esteem, and the interactions between the two are of relevance in bipolar symptoms. Clinical implications and future research directions are discussed. Explicit as well as implicit SE, and particularly their relationship, are relevant for mental health. Fluctuations in implicit SE may serve as an early indicator for risk of bipolarity. Psychotherapeutic approaches may be more suitable for one kind of SE challenge than the other. © 2013 The British Psychological Society.

Implicit Racial Biases in Preschool Children and Adults from Asia and Africa

ERIC Educational Resources Information Center

Qian, Miao K.; Heyman, Gail D.; Quinn, Paul C.; Messi, Francoise A.; Fu, Genyue; Lee, Kang

2016-01-01

This research used an Implicit Racial Bias Test to investigate implicit racial biases among 3- to 5-year-olds and adult participants in China (N = 213) and Cameroon (N = 257). In both cultures, participants displayed high levels of racial biases that remained stable between 3 and 5 years of age. Unlike adults, young children's implicit racial…

An improved semi-implicit method for structural dynamics analysis

NASA Technical Reports Server (NTRS)

Park, K. C.

1982-01-01

A semi-implicit algorithm is presented for direct time integration of the structural dynamics equations. The algorithm avoids the factoring of the implicit difference solution matrix and mitigates the unacceptable accuracy losses which plagued previous semi-implicit algorithms. This substantial accuracy improvement is achieved by augmenting the solution matrix with two simple diagonal matrices of the order of the integration truncation error.

The Implicit Relational Assessment Procedure as a Measure of Implicit Depression and the Role of Psychological Flexibility

ERIC Educational Resources Information Center

Hussey, Ian; Barnes-Holmes, Dermot

2012-01-01

A broad implicit measure of depressive emotional reactions was created by mapping the content of the depression scale from the Depression Anxiety and Stress Scale (DASS) on to the Implicit Relational Assessment Procedure (IRAP). Participants were asked to relate pairings of antecedents and emotional reactions that followed the formula "When X…

What We "Say" and What We "Think" about Female Managers: Explicit versus Implicit Associations of Women with Success

ERIC Educational Resources Information Center

Latu, Ioana M.; Stewart, Tracie L.; Myers, Ashley C.; Lisco, Claire G.; Estes, Sarah Beth; Donahue, Dana K.

2011-01-01

In two studies, we investigated implicit gender stereotypes of successful managers. Using an adaptation of the Implicit Association Test (IAT) named the Successful Manager IAT (SM-IAT) in Study 1, we found that male participants were more likely to implicitly associate men with successful manager traits and women with unsuccessful manager traits…

Implicit negotiation beliefs and performance: experimental and longitudinal evidence.

PubMed

Kray, Laura J; Haselhuhn, Michael P

2007-07-01

The authors argue that implicit negotiation beliefs, which speak to the expected malleability of negotiating ability, affect performance in dyadic negotiations. They expected negotiators who believe negotiating attributes are malleable (incremental theorists) to outperform negotiators who believe negotiating attributes are fixed (entity theorists). In Study 1, they gathered evidence of convergent and discriminant validity for the implicit negotiation belief construct. In Study 2, they examined the impact of implicit beliefs on the achievement goals that negotiators pursue. In Study 3, they explored the causal role of implicit beliefs on negotiation performance by manipulating negotiators' implicit beliefs within dyads. They also identified perceived ability as a moderator of the link between implicit negotiation beliefs and performance. In Study 4, they measured negotiators' beliefs in a classroom setting and examined how these beliefs affected negotiation performance and overall performance in the course 15 weeks later. Across all performance measures, incremental theorists outperformed entity theorists. Consistent with the authors' hypotheses, incremental theorists captured more of the bargaining surplus and were more integrative than their entity theorist counterparts, suggesting implicit theories are important determinants of how negotiators perform. Implications and future directions are discussed. Copyright 2007 APA, all rights reserved.

Adult age differences in perceptually based, but not conceptually based implicit tests of memory.

PubMed

Small, B J; Hultsch, D F; Masson, M E

1995-05-01

Implicit tests of memory assess the influence of recent experience without requiring awareness of remembering. Evidence concerning age differences on implicit tests of memory suggests small age differences in favor of younger adults. However, the majority of research examining this issue has relied upon perceptually based implicit tests. Recently, a second type of implicit test, one that relies upon conceptually based processes, has been identified. The pattern of age differences on this second type of implicit test is less clear. In the present study, we examined the pattern of age differences on one conceptually based (fact completion) and one perceptually based (stem completion) implicit test of memory, as well as two explicit tests of memory (fact and word recall). Tasks were administered to 403 adults from three age groups (19-34 years, 58-73 years, 74-89 years). Significant age differences in favor of the young were found on stem completion but not fact completion. Age differences were present for both word and fast recall. Correlational analyses examining the relationship of memory performance to other cognitive variables indicated that the implicit tests were supported by different components than the explicit tests, as well as being different from each other.

Implicit and Explicit Associations with Erotic Stimuli in Women with and Without Sexual Problems.

PubMed

van Lankveld, Jacques J D M; Bandell, Myrthe; Bastin-Hurek, Eva; van Beurden, Myra; Araz, Suzan

2018-02-20

Conceptual models of sexual functioning have suggested a major role for implicit cognitive processing in sexual functioning. The present study aimed to investigate implicit and explicit cognition in sexual functioning in women. Gynecological patients with (N = 38) and without self-reported sexual problems (N = 41) were compared. Participants performed two Single-Target Implicit Association Tests (ST-IAT), measuring the implicit association of visual erotic stimuli with attributes representing, respectively, valence and motivation. Participants also rated the erotic pictures that were shown in the ST-IATs on the dimensions of valence, attractiveness, and sexual excitement, to assess their explicit associations with these erotic stimuli. Participants completed the Female Sexual Functioning Index and the Female Sexual Distress Scale for continuous measures of sexual functioning, and the Hospital Anxiety and Depression Scale to assess depressive symptoms. Compared to nonsymptomatic women, women with sexual problems were found to show more negative implicit associations of erotic stimuli with wanting (implicit sexual motivation). Across both groups, stronger implicit associations of erotic stimuli with wanting predicted higher level of sexual functioning. More positive explicit ratings of erotic stimuli predicted lower level of sexual distress across both groups.

Investigating the predictive validity of implicit and explicit measures of motivation in problem-solving behavioural tasks.

PubMed

Keatley, David; Clarke, David D; Hagger, Martin S

2013-09-01

Research into the effects of individuals'autonomous motivation on behaviour has traditionally adopted explicit measures and self-reported outcome assessment. Recently, there has been increased interest in the effects of implicit motivational processes underlying behaviour from a self-determination theory (SDT) perspective. The aim of the present research was to provide support for the predictive validity of an implicit measure of autonomous motivation on behavioural persistence on two objectively measurable tasks. SDT and a dual-systems model were adopted as frameworks to explain the unique effects offered by explicit and implicit autonomous motivational constructs on behavioural persistence. In both studies, implicit autonomous motivation significantly predicted unique variance in time spent on each task. Several explicit measures of autonomous motivation also significantly predicted persistence. Results provide support for the proposed model and the inclusion of implicit measures in research on motivated behaviour. In addition, implicit measures of autonomous motivation appear to be better suited to explaining variance in behaviours that are more spontaneous or unplanned. Future implications for research examining implicit motivation from dual-systems models and SDT approaches are outlined. © 2012 The British Psychological Society.

Automatic affective-motivational regulation processes underlying supportive dyadic coping: the role of increased implicit positive attitudes toward communal goals in response to a stressed relationship partner.

PubMed

Koranyi, Nicolas; Hilpert, Peter; Job, Veronika; Bodenmann, Guy

2017-09-01

We examined the implicit affective mechanisms underlying provision of support in intimate dyads. Specifically, we hypothesized that in individuals with high relationship satisfaction, the perception that one's partner is stressed leads to increased implicit positive attitudes toward communal goals. In turn, this change in implicit attitudes facilitates supportive behavior. In two studies, we induced partner stress by instructing participants to either recall a situation where their partner was highly stressed (Study 1; N = 47 university students) or imagine a specific stressful event (excessive workload; Study 2; N = 85 university students). Subsequently, implicit attitudes toward communal goals were assessed with an Implicit Association Test. In both studies, we found that among participants with high relationship satisfaction partner stress increases preferences for communal goals. In addition, implicit preferences for communal goals predicted stronger inclinations to engage in supportive dyadic coping (Study 2). The current findings provide important insights into the implicit cognitive-affective mechanics of dyadic coping. Moreover, they can explain how people manage to avoid experiencing motivational conflicts between partner-oriented and self-oriented goals in situations characterized by high partner stress.

Examining Implicit Attitudes towards Exercisers with a Physical Disability

PubMed Central

Dionne, Cassandra D.; Gainforth, Heather L.; O'Malley, Deborah A.; Latimer-Cheung, Amy E.

2013-01-01

Background. Using measures of explicit attitudes, physical activity status has been established as a factor that reduces the stigma able-bodied people hold towards people with physical disabilities. This phenomenon is called the exerciser stereotype. However, whether the exerciser stereotype exists when using measures of implicit attitudes remains unknown. Objective. The aims of this study were to evaluate the prevalence of negative implicit attitudes towards people with physical disabilities and determine whether implicit attitudes towards people with physical disabilities were influenced by the exerciser stereotype. Methods. One hundred able-bodied participants (82 females, 18 males) completed two implicit association tests (IATs): the Disability-Attitudes IAT and the Disability-Activity IAT. The Disability-Attitudes IAT measured implicit attitudes towards people who were not disabled relative to disabled; the Disability-Activity IAT measured attitudes towards people with a physical disability who were active relative to inactive. Results. Results revealed that 83.8% of participants had negative implicit attitudes towards people with a disability. Participants held more positive attitudes towards active versus inactive people with a physical disability. Conclusions. The study findings indicate that the exerciser stereotype exists implicitly and may undermine negative attitudes towards people with physical disabilities. PMID:23710142

Cross-cultural evidence that the nonverbal expression of pride is an automatic status signal.

PubMed

Tracy, Jessica L; Shariff, Azim F; Zhao, Wanying; Henrich, Joseph

2013-02-01

To test whether the pride expression is an implicit, reliably developing signal of high social status in humans, the authors conducted a series of experiments that measured implicit and explicit cognitive associations between pride displays and high-status concepts in two culturally disparate populations--North American undergraduates and Fijian villagers living in a traditional, small-scale society. In both groups, pride displays produced strong implicit associations with high status, despite Fijian social norms discouraging overt displays of pride. Also in both groups, implicit and explicit associations between emotion expressions and status were dissociated; despite the cross-cultural implicit association between pride displays and high status, happy displays were, cross-culturally, the more powerful status indicator at an explicit level, and among Fijians, happy and pride displays were equally strongly implicitly associated with status. Finally, a cultural difference emerged: Fijians viewed happy displays as more deserving of high status than did North Americans, both implicitly and explicitly. Together, these findings suggest that the display and recognition of pride may be part of a suite of adaptations for negotiating status relationships, but that the high-status message of pride is largely communicated through implicit cognitive processes. 2013 APA, all rights reserved

Haptics-based dynamic implicit solid modeling.

PubMed

Hua, Jing; Qin, Hong

2004-01-01

This paper systematically presents a novel, interactive solid modeling framework, Haptics-based Dynamic Implicit Solid Modeling, which is founded upon volumetric implicit functions and powerful physics-based modeling. In particular, we augment our modeling framework with a haptic mechanism in order to take advantage of additional realism associated with a 3D haptic interface. Our dynamic implicit solids are semi-algebraic sets of volumetric implicit functions and are governed by the principles of dynamics, hence responding to sculpting forces in a natural and predictable manner. In order to directly manipulate existing volumetric data sets as well as point clouds, we develop a hierarchical fitting algorithm to reconstruct and represent discrete data sets using our continuous implicit functions, which permit users to further design and edit those existing 3D models in real-time using a large variety of haptic and geometric toolkits, and visualize their interactive deformation at arbitrary resolution. The additional geometric and physical constraints afford more sophisticated control of the dynamic implicit solids. The versatility of our dynamic implicit modeling enables the user to easily modify both the geometry and the topology of modeled objects, while the inherent physical properties can offer an intuitive haptic interface for direct manipulation with force feedback.

Implicit but not explicit self-esteem predicts future depressive symptomatology.

PubMed

Franck, Erik; De Raedt, Rudi; De Houwer, Jan

2007-10-01

To date, research on the predictive validity of implicit self-esteem for depressive relapse is very sparse. In the present study, we assessed implicit self-esteem using the Name Letter Preference Task and explicit self-esteem using the Rosenberg self-esteem scale in a group of currently depressed patients, formerly depressed individuals, and never depressed controls. In addition, we examined the predictive validity of explicit, implicit, and the interaction of explicit and implicit self-esteem in predicting future symptoms of depression in formerly depressed individuals and never depressed controls. The results showed that currently depressed individuals reported a lower explicit self-esteem as compared to formerly depressed individuals and never depressed controls. In line with previous research, all groups showed a positive implicit self-esteem not different from each other. Furthermore, after controlling for initial depressive symptomatology, implicit but not explicit self-esteem significantly predicted depressive symptoms at six months follow-up. Although implicit self-esteem assessed with the Name Letter Preference Test was not different between formerly depressed individuals and never depressed controls, the findings suggest it is an interesting variable in the study of vulnerability for depression relapse.

Using behavior-analytic implicit tests to assess sexual interests among normal and sex-offender populations

PubMed Central

Roche, Bryan; O’Reilly, Anthony; Gavin, Amanda; Ruiz, Maria R.; Arancibia, Gabriela

2012-01-01

Background The development of implicit tests for measuring biases and behavioral predispositions is a recent development within psychology. While such tests are usually researched within a social-cognitive paradigm, behavioral researchers have also begun to view these tests as potential tests of conditioning histories, including in the sexual domain. Objective The objective of this paper is to illustrate the utility of a behavioral approach to implicit testing and means by which implicit tests can be built to the standards of behavioral psychologists. Design Research findings illustrating the short history of implicit testing within the experimental analysis of behavior are reviewed. Relevant parallel and overlapping research findings from the field of social cognition and on the Implicit Association Test are also outlined. Results New preliminary data obtained with both normal and sex offender populations are described in order to illustrate how behavior-analytically conceived implicit tests may have potential as investigative tools for assessing histories of sexual arousal conditioning and derived stimulus associations. Conclusion It is concluded that popular implicit tests are likely sensitive to conditioned and derived stimulus associations in the history of the test-taker rather than ‘unconscious cognitions’, per se. PMID:24693346

Evaluating bis(2-ethylhexyl) methanediphosphonic acid (H 2DEH[MDP]) based polymer ligand film (PLF) for plutonium and uranium extraction

DOE PAGES

Rim, Jung H.; Armenta, Claudine E.; Gonzales, Edward R.; ...

2015-09-12

This paper describes a new analyte extraction medium called polymer ligand film (PLF) that was developed to rapidly extract radionuclides. PLF is a polymer medium with ligands incorporated in its matrix that selectively and quickly extracts analytes. The main focus of the new technique is to shorten and simplify the procedure for chemically isolating radionuclides for determination through alpha spectroscopy. The PLF system was effective for plutonium and uranium extraction. The PLF was capable of co-extracting or selectively extracting plutonium over uranium depending on the PLF composition. As a result, the PLF and electrodeposited samples had similar alpha spectra resolutions.

Framing (implicitly) matters: the role of religion in attitudes toward immigrants and Muslims in Denmark.

PubMed

Anderson, Joel; Antalíková, Radka

2014-12-01

Denmark is currently experiencing the highest immigration rate in its modern history. Population surveys indicate that negative public attitudes toward immigrants actually stem from attitudes toward their (perceived) Islamic affiliation. We used a framing paradigm to investigate the explicit and implicit attitudes of Christian and Atheist Danes toward targets framed as Muslims or as immigrants. The results showed that explicit and implicit attitudes were more negative when the target was framed as a Muslim, rather than as an immigrant. Interestingly, implicit attitudes were qualified by the participants' religion. Specifically, analyses revealed that Christians demonstrated more negative implicit attitudes toward immigrants than Muslims. Conversely, Atheists demonstrated more negative implicit attitudes toward Muslims than Atheists. These results suggest a complex relationship between religion, and implicit and explicit prejudice. Both the religious affiliation of the perceiver and the perceived religious affiliation of the target are key factors in social perception. © 2014 Scandinavian Psychological Associations and John Wiley & Sons Ltd.

Stability of and Changes in Implicit Motives. A Narrative Review of Empirical Studies

PubMed Central

Denzinger, Ferdinand; Brandstätter, Veronika

2018-01-01

Although growing research indicates that certain personality traits change over the lifespan, implicit motives are often deemed to be rather stable personality characteristics. Researchers have been interested in implicit motives for several decades, but our understanding of how these dispositions change still lacks clarity. This article gives an overview and a discussion of the current evidence for the stability of and the changes in implicit motives. After elaborating on the theoretical background of the motive construct and its measurement, we present an overview of studies that have investigated the trainability of implicit motives and their dispositional stability and changes using cross-sectional and longitudinal methods. Although the results are inconclusive concerning the direction of change, the reviewed studies suggest that implicit motives adapt to life circumstances much like other personality traits. This review sets out to contribute to a better understanding of the functioning of implicit motives and to present a roadmap for further research. PMID:29887818

White and Black American Children’s Implicit Intergroup Bias

PubMed Central

Newheiser, Anna-Kaisa; Olson, Kristina R.

2011-01-01

Despite a decline in explicit prejudice, adults and children from majority groups (e.g., White Americans) often express bias implicitly, as assessed by the Implicit Association Test. In contrast, minority-group (e.g., Black American) adults on average show no bias on the IAT. In the present research, representing the first empirical investigation of whether Black children’s IAT responses parallel those of Black adults, we examined implicit bias in 7–11-year-old White and Black American children. Replicating previous findings with adults, whereas White children showed a robust ingroup bias, Black children showed no bias. Additionally, we investigated the role of valuing status in the development of implicit bias. For Black children, explicit preference for high status predicted implicit outgroup bias: Black children who explicitly expressed high preference for rich (vs. poor) people showed an implicit preference for Whites comparable in magnitude to White children’s ingroup bias. Implications for research on intergroup bias are discussed. PMID:22184478

Motivated independence? Implicit party identity predicts political judgments among self-proclaimed Independents.

PubMed

Hawkins, Carlee Beth; Nosek, Brian A

2012-11-01

Reporting an Independent political identity does not guarantee the absence of partisanship. Independents demonstrated considerable variability in relative identification with Republicans versus Democrats as measured by an Implicit Association Test (IAT; M = 0.10, SD = 0.47). To test whether this variation predicted political judgment, participants read a newspaper article describing two competing welfare (Study 1) or special education (Study 2) policies. The authors manipulated which policy was proposed by which party. Among self-proclaimed Independents, those who were implicitly Democratic preferred the liberal welfare plan, and those who were implicitly Republican preferred the conservative welfare plan. Regardless of the policy details, these implicit partisans preferred the policy proposed by "their" party, and this effect occurred more strongly for implicit than explicit plan preference. The authors suggest that implicitly partisan Independents may consciously override some partisan influence when making explicit political judgments, and Independents may identify as such to appear objective even when they are not.

Mirrors, masks, and motivation: implicit and explicit self-focused attention influence effort-related cardiovascular reactivity.

PubMed

Silvia, Paul J

2012-07-01

Using motivational intensity theory as a framework, three experiments examined how implicit self-focus (manipulated with masked first-name priming) and explicit self-focus (manipulated with a large mirror) influence effort-related cardiovascular activity, particularly systolic blood pressure reactivity. Theories of self-focused attention suggest that both implicit and explicit self-focus bring about self-evaluation and thus make meeting a goal more important. For a "do your best" task of unfixed difficulty, implicit and explicit self-focus both increased effort (Experiment 1) compared to a control condition. For a task that varied in difficulty, implicit and explicit self-focus promoted more effort as the task became increasingly hard (Experiments 2 and 3). Taken together, the findings suggest that implicit and explicit self-processes share a similar motivational architecture. The discussion explores the value of integrating motivational intensity theory with self-awareness theory and considers the emerging interest in implicit aspects of effort regulation. Copyright © 2012 Elsevier B.V. All rights reserved.

The Role of Generalized Explicit and Implicit Guilt and Shame in Interpersonal Traumatization and Posttraumatic Stress Disorder.

PubMed

Bockers, Estelle; Roepke, Stefan; Michael, Lars; Renneberg, Babette; Knaevelsrud, Christine

2016-02-01

Posttraumatic stress disorder (PTSD) and interpersonal traumatization are frequently associated with trauma-related guilt and shame. However, research on generalized guilt and shame in PTSD is lacking. The aim of this study was to investigate generalized explicit and implicit guilt and shame in interpersonal traumatization and PTSD. Interpersonally traumatized women either with PTSD (n = 28) or without PTSD (n = 32) and 32 nontraumatized women completed the Test of Self-Conscious Affect-3 and the Implicit Association Test to measure explicit and implicit guilt and shame. Explicit guilt and shame were significantly higher in women with PTSD than in traumatized women without PTSD. Traumatized women without PTSD showed significantly higher levels of explicit guilt and shame than nontraumatized women did. PTSD was associated with implicit guilt but not implicit shame. In addition to trauma-related guilt and shame, generalized explicit guilt and shame and implicit guilt seem to play a crucial role in PTSD.