A Novel Scoring Based Distributed Protein Docking Application to Improve Enrichment

Molecular docking is a computational technique which predicts the binding energy and the preferred binding mode of a ligand to a protein target. Virtual screening is a tool which uses docking to investigate large chemical libraries to identify ligands that bind favorably to a protein target. We have developed a novel scoring based distributed protein docking application to improve enrichment in virtual screening. The application addresses the issue of time and cost of screening in contrast to conventional systematic parallel virtual screening methods in two ways. Firstly, it automates the process of creating and launching multiple independent dockings on a high performance computing cluster. Secondly, it uses a N˙ aive Bayes scoring function to calculate binding energy of un-docked ligands to identify and preferentially dock (Autodock predicted) better binders. The application was tested on four proteins using a library of 10,573 ligands. In all the experiments, (i). 200 of the 1000 best binders are identified after docking only 14% of the chemical library, (ii). 9 or 10 best-binders are identified after docking only 19% of the chemical library, and (iii). no significant enrichment is observed after docking 70% of the chemical library. The results show significant increase in enrichment of potential drug leads in early rounds of virtual screening

Associations between psychopathy and the trait meta-mood scale in incarcerated males:A combined latent variable- and person-centered approach

The present study sought to replicate and extend current knowledge on the relevance of emotion regulation (ER) for psychopathy. In a large sample of incarcerated adult males (N = 578), latent profile analysis (LPA) and structural equation modeling (SEM) were employed to examine person- and variable-centered associations between self-reported ER and both self-report and clinical ratings of psychopathy. With LPA, participants were classified into three profiles corresponding to low, medium, and high ER. The low-ER profile displayed higher affective traits across psychopathy assessments compared with the other profiles. The same pattern of findings was evident for overt behavioral features of psychopathy, but not for interpersonal traits. SEM results were consistent with LPA findings: interpersonal (positively), affective, and lifestyle (negatively) facets had unique associations with a superordinate ER latent variable. Findings replicate and extend prior associations between psychopathy and ER and suggest differential links between ER and affective and interpersonal traits of psychopathy

Factor Structure of the Psychopathic Personality Inventory (PPI): Findings From a Large Incarcerated Sample

Exploratory factor analysis (EFA) of the Psychopathic Personality Inventory (PPI; S. O. Lilienfeld, 1990; S. O. Lilienfeld & B. P. Andrews, 1996) with a community sample has suggested that the PPI subscales may comprise 2 higher order factors (S. D. Benning, C. J. Patrick, B. M. Hicks, D. M. Blonigen, & R. F. Krueger, 2003). However, substantive and structural evidence raises concerns about the viability of this 2-factor model, particularly in offender populations. The authors attempted to replicate the S. D. Benning et al. 2-factor solution using a large (N= 1,224) incarcerated male sample. Confirmatory factor analysis of this model resulted in poor model fit. Similarly, using the same EFA procedures as did S. D. Benning et al., the authors found little evidence for a 2-factor model. When they followed the recommendations of J.-W. van Prooijen and W. A. van der Kloot (2001) for recovering EFA solutions, model fit results provided some evidence that a 3-factor EFA solution could be recovered via confirmatory factor analysis

Social Reward Questionnaire – Adolescent Version and its association with callous-unemotional traits

This article describes a study in which the adult Social Reward Questionnaire is adapted for use with adolescents

Happiness, environmental protection and market economy

The manufacturing sector is leaving the West for Asia’s low wages and good working culture. Europe would be better off keeping these manufacturing activities, slowing down wage inflation and what is more, letting a young, cheaper workforce from the East settle down within their borders. This would aid in preserving the diverse economic structure which has been characteristic for Europe.Beside the economic growth there are two more concepts which have turned into the “holy cows” of economics during the last fifty years. One is the need to constantly improve labor productivity and the other is increasing competitiveness of nations. The high labor productivity of some countries, induces severe unemployment in the globalized world. In the other hand it is high time we understood that it is not competition, but cooperation that brings more happiness to humanity.Should we still opt for “happiness” and “sanity”, it is quite obvious that we all should, in economists’ terms, define our individual welfare functions corresponding to our own set of values, staying free from the influence of media, advertisements and fashion. The cornerstone to all this is the intelligent citizen who prefers local goods and services

Pursuing Antiracist Public Policy Education: An Example Connecting the Racist History of Housing Policy to Contemporary Inequity

We review the antiracism concept and contextualize it in Extension public policy education and the Extension system itself. Despite public policy education having a long history in Extension on a wide variety of issues, missing from this programming is the pursuit of antiracism. As a programmatic example, we review some historical causes of present-day housing inequities and an associated example approach for pursuing antiracism in housing policy education. Finally, we conclude by noting additional opportunities to pursue antiracism in Extension public policy education. In doing so, we emphasize that public policy education cannot be “nonracist” if it is not antiracist

The construct of psychopathy in a Chilean prison population

Objective: To test the four-factor model of the Hare Psychopathy Checklist-Revised (PCL-R) empirical construct of psychopathy in a Chilean prison population by using instruments that supply different types of data. Methods: Two hundred and nine male inmates of the Prison of Los Andes, Chile, were evaluated. Confirmatory factor analysis was carried out with the PCL-R and the Self-Report of Psychopathy-III-Short Form (SRP-III-SF). Results: The distributions of total PCL-R and SRP-III-SF scores were normal (Kolmorogov-Smirnov [K-S] = 1.04, p = 0.230; K-S = 0.812, p = 0.525, respectively), with means of 20.9±6.8 for the former and 61.6±15.2 for the latter. Model fit was good for the PCL-R (Tucker Lewis index [TLI] = 0.96; root mean square error of approximation [RMSEA] = 0.04) and for the SRP-SF (TLI = 0.94, RMSEA = 0.04). Conclusions: The results obtained with the PCL-R and the SRP-SF showed adequate fit to the empirical four-factor model of psychopathy and support this model. As foreseeable, fit was better for the PCL-R, which combines several sources of information.Facultad de Ciencias Médica

Psychopathy as a clinical and empirical construct.

Abstract In this review, we focus on two major influences on current conceptualizations of psychopathy: one clinical, with its origins largely in the early case studies of Cleckley, and the other empirical, the result of widespread use of the Hare Psychopathy Checklist-Revised (PCL-R) for assessment purposes. Some investigators assert that the PCL-R, ostensibly based on Cleckley's work, has "drifted" from the construct described in his Clinical Profile. We evaluate this profile, note its basis in an unrepresentative sample of patients, and suggest that its literal and uncritical acceptance by the research community has become problematical. We also argue that the idea of construct "drift" is irrelevant to current conceptualizations of psychopathy, which are better informed by the extensive empirical research on the integration of structural, genetic, developmental, personality, and neurobiological research findings than by rigid adherence to early clinical formulations. We offer some suggestions for future research on psychopathy

Neural origins of human sickness in interoceptive responses to inflammation

BACKGROUND: Inflammation is associated with psychological, emotional, and behavioral disturbance, known as sickness behavior. Inflammatory cytokines are implicated in coordinating this central motivational reorientation accompanying peripheral immunologic responses to pathogens. Studies in rodents suggest an afferent interoceptive neural mechanism, although comparable data in humans are lacking. METHODS: In a double-blind, randomized crossover study, 16 healthy male volunteers received typhoid vaccination or saline (placebo) injection in two experimental sessions. Profile of Mood State questionnaires were completed at baseline and at 2 and 3 hours. Two hours after injection, participants performed a high-demand color word Stroop task during functional magnetic resonance imaging. Blood samples were performed at baseline and immediately after scanning. RESULTS: Typhoid but not placebo injection produced a robust inflammatory response indexed by increased circulating interleukin-6 accompanied by a significant increase in fatigue, confusion, and impaired concentration at 3 hours. Performance of the Stroop task under inflammation activated brain regions encoding representations of internal bodily state. Spatial and temporal characteristics of this response are consistent with interoceptive information flow via afferent autonomic fibers. During performance of this task, activity within interoceptive brain regions also predicted individual differences in inflammation-associated but not placebo-associated fatigue and confusion. Maintenance of cognitive performance, despite inflammation-associated fatigue, led to recruitment of additional prefrontal cortical regions. CONCLUSIONS: These findings suggest that peripheral infection selectively influences central nervous system function to generate core symptoms of sickness and reorient basic motivational states. PMID:19409533[PubMed - indexed for MEDLINE] PMCID: PMC2885492Free PMC Articl