Knowledge Questions from Knowledge Graphs

We address the novel problem of automatically generating quiz-style knowledge questions from a knowledge graph such as DBpedia. Questions of this kind have ample applications, for instance, to educate users about or to evaluate their knowledge in a specific domain. To solve the problem, we propose an end-to-end approach. The approach first selects a named entity from the knowledge graph as an answer. It then generates a structured triple-pattern query, which yields the answer as its sole result. If a multiple-choice question is desired, the approach selects alternative answer options. Finally, our approach uses a template-based method to verbalize the structured query and yield a natural language question. A key challenge is estimating how difficult the generated question is to human users. To do this, we make use of historical data from the Jeopardy! quiz show and a semantically annotated Web-scale document collection, engineer suitable features, and train a logistic regression classifier to predict question difficulty. Experiments demonstrate the viability of our overall approach

Ribosomal oxygenases are structurally conserved from prokaryotes to humans

2-Oxoglutarate (2OG)-dependent oxygenases have important roles in the regulation of gene expression via demethylation of N-methylated chromatin components1,2 and in the hydroxylation of transcription factors3 and splicing factor proteins4. Recently, 2OG-dependent oxygenases that catalyse hydroxylation of transfer RNA5,6,7 and ribosomal proteins8 have been shown to be important in translation relating to cellular growth, TH17-cell differentiation and translational accuracy9,10,11,12. The finding that ribosomal oxygenases (ROXs) occur in organisms ranging from prokaryotes to humans8 raises questions as to their structural and evolutionary relationships. In Escherichia coli, YcfD catalyses arginine hydroxylation in the ribosomal protein L16; in humans, MYC-induced nuclear antigen (MINA53; also known as MINA) and nucleolar protein 66 (NO66) catalyse histidine hydroxylation in the ribosomal proteins RPL27A and RPL8, respectively. The functional assignments of ROXs open therapeutic possibilities via either ROX inhibition or targeting of differentially modified ribosomes. Despite differences in the residue and protein selectivities of prokaryotic and eukaryotic ROXs, comparison of the crystal structures of E. coli YcfD and Rhodothermus marinus YcfD with those of human MINA53 and NO66 reveals highly conserved folds and novel dimerization modes defining a new structural subfamily of 2OG-dependent oxygenases. ROX structures with and without their substrates support their functional assignments as hydroxylases but not demethylases, and reveal how the subfamily has evolved to catalyse the hydroxylation of different residue side chains of ribosomal proteins. Comparison of ROX crystal structures with those of other JmjC-domain-containing hydroxylases, including the hypoxia-inducible factor asparaginyl hydroxylase FIH and histone Nε-methyl lysine demethylases, identifies branch points in 2OG-dependent oxygenase evolution and distinguishes between JmjC-containing hydroxylases and demethylases catalysing modifications of translational and transcriptional machinery. The structures reveal that new protein hydroxylation activities can evolve by changing the coordination position from which the iron-bound substrate-oxidizing species reacts. This coordination flexibility has probably contributed to the evolution of the wide range of reactions catalysed by oxygenases

Stringency of the 2-His–1-Asp Active-Site Motif in Prolyl 4-Hydroxylase

The non-heme iron(II) dioxygenase family of enzymes contain a common 2-His–1-carboxylate iron-binding motif. These enzymes catalyze a wide variety of oxidative reactions, such as the hydroxylation of aliphatic C–H bonds. Prolyl 4-hydroxylase (P4H) is an α-ketoglutarate-dependent iron(II) dioxygenase that catalyzes the post-translational hydroxylation of proline residues in protocollagen strands, stabilizing the ensuing triple helix. Human P4H residues His412, Asp414, and His483 have been identified as an iron-coordinating 2-His–1-carboxylate motif. Enzymes that catalyze oxidative halogenation do so by a mechanism similar to that of P4H. These halogenases retain the active-site histidine residues, but the carboxylate ligand is replaced with a halide ion. We replaced Asp414 of P4H with alanine (to mimic the active site of a halogenase) and with glycine. These substitutions do not, however, convert P4H into a halogenase. Moreover, the hydroxylase activity of D414A P4H cannot be rescued with small molecules. In addition, rearranging the two His and one Asp residues in the active site eliminates hydroxylase activity. Our results demonstrate a high stringency for the iron-binding residues in the P4H active site. We conclude that P4H, which catalyzes an especially demanding chemical transformation, is recalcitrant to change

Protocol: Personality assessment as a support for referral and case-work in treatment for substance use disorders (PASRC-study)

<p>Abstract</p> <p>Background</p> <p>Assessment of co-morbid personality disorders in substance use disorders may lead to important insights concerning individual patients. However, little is known about the potential value of routine personality disorder assessment in a clinical context.</p> <p>Methods</p> <p>Patients are adults with past-year substance dependence seeking treatment at a centralized intake unit for substance abusers in the City of Copenhagen. A randomized controlled trial of assessment of personality disorders and individual feedback vs. a general life situation interview. Patients are followed at 3 and 6 months post-treatment</p> <p>Discussion</p> <p>If routine personality assessment improves outcomes of substance abuse treatment, the clinical implication is to increase the use of personality disorder assessment in substance abuse treatment settings.</p> <p>Trial registration</p> <p>Current controlled trials ISRCTN39851689</p

A three-year cohort study of the relationships between coping, job stress and burnout after a counselling intervention for help-seeking physicians

<p>Abstract</p> <p>Background</p> <p>Knowledge about important factors in reduction of burnout is needed, but there is a dearth of burnout intervention program studies and their effects among physicians. The present three-year follow-up study aimed to investigate the roles of coping strategies, job stress and personality traits in burnout reduction after a counselling intervention for distressed physicians.</p> <p>Methods</p> <p>227 physicians who attended a counselling intervention for burnout at the Resource Centre Villa Sana, Norway in 2003-2005, were followed with self-report assessments at baseline, one-year, and three-year follow-up. Main outcome measures were emotional exhaustion (one dimension of burnout), job stress, coping strategies and neuroticism. Changes in these measures were analyzed with repeated measures ANOVA. Temporal relationships between changes were examined using structural modelling with cross-lagged and synchronous panel models.</p> <p>Results</p> <p>184 physicians (81%, 83 men, 101 women) completed the three-year follow-up assessment. Significantly reduced levels of emotional exhaustion, job stress, and emotion-focused coping strategies from baseline to one year after the intervention, were maintained at three-year follow-up.</p> <p>Panel modelling indicated that changes in emotion-focused coping (z = 4.05, p < 0.001) and job stress (z = 3.16, p < 0.01) preceded changes in emotional exhaustion from baseline to three-year follow-up. A similar pattern was found from baseline to one-year follow-up.</p> <p>Conclusion</p> <p>A sequential relationship indicated that reduction in emotion-focused coping and in job stress preceded reduction in emotional exhaustion. As a consequence, coping strategies and job stress could be important foci in intervention programs that aim to reduce or prevent burnout in help-seeking physicians.</p

The development of compassionate engagement and action scales for self and others

Background Studies of the value of compassion on physical and mental health and social relationships have proliferated in the last 25 years. Although, there are several conceptualisations and measures of compassion, this study develops three new measures of compassion competencies derived from an evolutionary, motivational approach. The scales assess 1. the compassion we experience for others, 2. the compassion we experience from others, and 3. self-compassion based on a standard definition of compassion as a ‘sensitivity to suffering in self and others with a commitment to try to alleviate and prevent it’. We explored these in relationship to other compassion scales, self-criticism, depression, anxiety, stress and well-being. Methods Participants from three different countries (UK, Portugal and USA) completed a range of scales including compassion for others, self-compassion, self-criticism, shame, depression, anxiety and stress with the newly developed ‘The Compassionate Engagement and Actions’ scale. Results All three scales have good validity. Interestingly, we found that the three orientations of compassion are only moderately correlated to one another (r < .5). We also found that some elements of self-compassion (e.g., being sensitive to, and moved by one’s suffering) have a complex relationship with other attributes of compassion (e.g., empathy), and with depression, anxiety and stress. A path-analysis showed that self-compassion is a significant mediator of the association between self-reassurance and well-being, while self-criticism has a direct effect on depressive symptoms, not mediated by self-compassion. Discussion Compassion evolved from caring motivation and in humans is associated with a range of different socially intelligent competencies. Understanding how these competencies can be inhibited and facilitated is an important research endeavour. These new scales were designed to assess these competencies. Conclusions This is the first study to measure the three orientations of compassion derived from an evolutionary model of caring motivation with specified competencies. Our three new measures of compassion further indicate important complex relationships between different potentiation’s of compassion, well-being, and vulnerability to psychopathologies.N/