Computer simulation in low-temperature plasma physics: future challenges

Computer simulations can be carried out with various aims. Perhaps the most challenging is prediction under conditions where experiments are difficult or inaccessible, especially when failure to predict adequately may have unhappy consequences. There is, probably, not much confidence at present in the capability of low-temperature plasma physics simulations in such a context. Other fields have attempted to meet this challenge using a collection of techniques collectively known as Verification and Validation, or V&V. These are methods for enhancing confidence in the correctness and fidelity of computer simulations. This paper surveys these techniques and discusses their application to improvements of simulation capability in low-temperature plasma physics

(Re)Moralizing the suicide debate

Contemporary approaches to the study of suicide tend to examine suicide as a medical or public health problem rather than a moral problem, avoiding the kinds of judgements that have historically characterised discussions of the phenomenon. But morality entails more than judgement about action or behaviour, and our understanding of suicide can be enhanced by attending to its cultural, social, and linguistic connotations. In this work, I offer a theoretical reconstruction of suicide as a form of moral experience that delineates five distinct, yet interrelated domains of understanding – the temporal, the relational, the existential, the ontological, and the linguistic. Attention to each of these domains, I argue, not only enriches our understanding of the moral realm, but provides a heuristic for examining the moral traditions and practices which constitute contemporary understandings of suicide. Keywords: Suicide; philosophy; social values; humanitie

Regulation of conditional gene expression by coupled transcription repression and RNA degradation

Gene expression is determined by a combination of transcriptional and post-transcriptional regulatory events that were thought to occur independently. This report demonstrates that the genes associated with the Snf3p–Rgt2p glucose-sensing pathway are regulated by interconnected transcription repression and RNA degradation. Deletion of the dsRNA-specific ribonuclease III Rnt1p increased the expression of Snf3p–Rgt2p-associated transcription factors in vivo and the recombinant enzyme degraded their messenger RNA in vitro. Surprisingly, Rnt1ps effect on gene expression in vivo was both RNA and promoter dependent, thus linking RNA degradation to transcription. Strikingly, deletion of RNT1-induced promoter-specific transcription of the glucose sensing genes even in the absence of RNA cleavage signals. Together, the results presented here support a model in which co-transcriptional RNA degradation increases the efficiency of gene repression, thereby allowing an effective cellular response to the continuous changes in nutrient concentrations

The enhancement of stress-related memory by glucocorticoids depends on synapsin-Ia/Ib

The activation of glucocorticoid receptors (GR) by glucocorticoids increases stress-related memory through the activation of the MAPK signaling pathway and the downstream transcription factor Egr-1. Here, using converging in vitro and in vivo approaches, respectively, GR-expressing cell lines, culture of hippocampal neurons, and GR genetically modified mice (GRNesCre), we identified synapsin-Ia/Ib as one of the effectors of the glucocorticoid signaling cascade. Stress and glucocorticoid-induced activation of the GR modulate synapsin-Ia/Ib through two complementary mechanisms. First, glucocorticoids driving Egr-1 expression increase the expression of synapsin-Ia/Ib, and second, glucocorticoids driving MAPK activation increase its phosphorylation. Finally, we showed that blocking fucosylation of synapsin-Ia/Ib in the hippocampus inhibits its expression and prevents the glucocorticoid-mediated increase in stress-related memory. In conclusion, our data provide a complete molecular pathway (GR/Egr-1/MAPK/Syn-Ia/Ib) through which stress and glucocorticoids enhance the memory of stress-related events and highlight the function of synapsin-Ia/Ib as molecular effector of the behavioral effects of stress

BRITAIN, THE TWO WORLD WARS, AND THE PROBLEM OF NARRATIVE

AbstractThe concept of coming to terms with the past originated in post-1945 West Germany but such historical therapy is evident in all the belligerent countries. In that process, the two world wars are intricately connected, each seen refractively through the prism of the other. This article focuses on Britain whose national obsession with the two world wars is particularly acute. The first and second sections suggest that British public discourse has been able to construct a satisfying narrative of 1939–45 but not of 1914–18, meaning a narrative that has both a clear beginning, middle, and end and also a stark moral meaning. Viable narratives draw on the events themselves, the words used to conceptualize them, and the interpretations of 'instant' histories and memoirs. The third section argues that the elevation of 1939–45 in national discourse as our ‘finest hour’ (Churchill) has aggravated the problematic nature of 1914–18 for the British. In the wake of Brexit, the last section argues that Britain – unlike France and Germany – has found it difficult to move on from the era of the two world wars by locating these conflicts in a more positive narrative of the twentieth century as the eventual triumph of European integration.</jats:p

Physicians’ views and experiences of discussing weight management within routine clinical consultations: A thematic synthesis

Objective To systematically search and synthesise qualitative studies of physicians’ views and experiences of discussing weight management within a routine consultation. Methods A systematic search of four electronic databases identified 11,169 articles of which 16 studies met inclusion criteria. Quality was appraised using the Critical Appraisal Skills Programme tool and a thematic synthesis conducted of extracted data. Results Four analytical themes were found: (1) physicians’ pessimism about patients’ weight loss success (2) physicians’ feel hopeless and frustrated (3) the dual nature of the physician-patient relationship (4) who should take responsibility for weight management. Conclusion Despite clinical recommendations barriers remain during consultations between physicians and patients about weight management. Many of these barriers are potentially modifiable