A failure management prototype: DR/Rx

This failure management prototype performs failure diagnosis and recovery management of hierarchical, distributed systems. The prototype, which evolved from a series of previous prototypes following a spiral model for development, focuses on two functions: (1) the diagnostic reasoner (DR) performs integrated failure diagnosis in distributed systems; and (2) the recovery expert (Rx) develops plans to recover from the failure. Issues related to expert system prototype design and the previous history of this prototype are discussed. The architecture of the current prototype is described in terms of the knowledge representation and functionality of its components

Interaction of short modified peptides deriving from glycoprotein gp36 of feline immunodeficiency virus with phospholipid membranes

A tryptophan-rich octapeptide, C8 (Ac-Trp-Glu-Asp-Trp-Val-Gly-Trp-Ile-NH2), modelled on the membrane-proximal external region of the feline immunodeficiency virus (FIV) gp36 glycoprotein ectodomain, exhibits potent antiviral activity against FIV. A mechanism has been proposed by which the peptide, being positioned on the surface of the cell membrane, inhibits its fusion with the virus. In the present work, peptide–lipid interactions of C8 with dimyristoyl phosphatidylcholine liposomes are investigated using electron spin resonance spectroscopy of spin-labelled lipids. Three other peptides, obtained from modifications of C8, have also been investigated, in an attempt to clarify the essential molecular features of the interactions involving the tryptophan residues. The results show that C8 adsorbs strongly on the bilayer surface. Membrane binding requires not only the presence of the Trp residues in the sequence, but also their common orientation on one side of the peptide that is engendered by the WX2 WX2 W motif. Membrane interaction correlates closely with peptide antiviral activity, indicating that the membrane is essential in stabilizing the peptide conformation that will be able to inhibit viral infection

Family coordination in families who have a child with autism spectrum disorder

Little is known about the interactions of families where there is a child with autism spectrum disorder (ASD). The present study applies the Lausanne Trilogue Play (LTP) to explore both its applicability to this population as well as to assess resources and areas of deficit in these families. The sample consisted of 68 families with a child with ASD, and 43 families with a typically developing (TD) child. With respect to the global score for family coordination there were several negative correlations: the more severe the symptoms (based on the child’s ADOS score), the more family coordination was dysfunctional. This correlation was particularly high when parents had to play together with the child. In the parts in which only one of the parents played actively with the child, while the other was simply present, some families did achieve scores in the functional range, despite the child’s symptom severity. The outcomes are discussed in terms of their clinical implications both for assessment and for interventio

A conceptual classification of parents’ attributions of the role of food advertising in children’s diets

Background: High levels of child obesity are triggering growing concerns about the prevalence and effects of food advertising targeted at children. Efforts to address this advertising are confounded by the expanding repertoire of media and promotional techniques used to reach and attract children. The present study explored parents’ views on food marketing and the strategies parents employ when attempting to ameliorate its effects. As part of an online survey of Australian parents’ attitudes towards a range of food advertisements, respondents were invited to provide additional comment in an open-ended question. The question was optional and asked “Are there any other comments you would like to make?”. One in five of the survey respondents (18%; n = 235) elected to answer this question by discussing their views on food advertising and children’s diets. The responses were imported into NVivo10 for coding and analysis. A grounded approach was used to draw meaning from the data and develop a proposed conceptual classification of parents’ attributions relating to food advertising and its consequences.Results: The majority of responses related to the negative perceived effects of unhealthy food advertising on children’s diets, with few respondents considering such advertisements to be innocuous. The responses were classified into four conceptual categories reflecting differing attitudes to advertising (negative to neutral) and varying levels of locus of control (low to high). The typical characteristics of parents allocated to the four categories exhibited variation according to weight status, television viewing habits, education level, and family size. The largest number of responses was coded to the category characterized by a negative attitude toward food advertising and a low locus of control. Parents in this category were more likely than others to be overweight/obese and heavy television viewers. Parents in the negative attitude to advertising and high locus of control category nominated a variety of parenting practices that could form the basis of parent education interventions. Conclusions: The results suggest that many Australian parents may feel disempowered in the face of high levels of advertising for unhealthy foods. The current voluntary regulatory code appears to be inadequate in scope and coverage to address this situation

Interaction between PPARA genotype and β-blocker treatment influences clinical outcomes following acute coronary syndromes

β-blockers (BB) are strongly recommended after an acute coronary syndrome (ACS), although all patients may not benefit. Causes for variable patient responses to BB are unknown. Given that myocardial ischemia and BB influence metabolic processes regulated by peroxisome proliferator-activated receptor α (PPARα), we hypothesized that interactions between polymorphisms of the PPARα gene (PPARA) and BB treatment would influence clinical outcome following ACS

Subjective well-being and engagement in arts, culture and sport

This paper explores the relationship between engagement in arts, culture and sport, and subjective well-being, contributing to our understanding of the leisure experience, and cultural value, of these activities. Ordered probit analysis of UK data from wave 2 (2010-11) of Understanding Society , provides evidence in support of a wide range of cultural goods generating positive leisure experience, reflected in overall (life, general happiness) and domain (leisure) satisfaction. Frequency of engagement is central to certain activities: only regular participation in arts activities and sport generates positive effects. In contrast, arts events are positive irrespective of frequency. The findings also indicate even less frequent engagement in activities exhibiting cultural characteristics, e.g. museums/historical sites, has positive association with satisfaction. Finally, although employment has a negative association with leisure satisfaction, engagement in leisure activities is not found to spillover into job satisfaction (with the exception of certain sports). This suggests individuals consider work and leisure (including quality of leisure time) separately

<i>ABCB1</i> (MDR1) induction defines a common resistance mechanism in paclitaxel- and olaparib-resistant ovarian cancer cells

BACKGROUND: Clinical response to chemotherapy for ovarian cancer is frequently compromised by the development of drug-resistant disease. The underlying molecular mechanisms and implications for prescription of routinely prescribed chemotherapy drugs are poorly understood. METHODS: We created novel A2780-derived ovarian cancer cell lines resistant to paclitaxel and olaparib following continuous incremental drug selection. MTT assays were used to assess chemosensitivity to paclitaxel and olaparib in drug-sensitive and drug-resistant cells±the ABCB1 inhibitors verapamil and elacridar and cross-resistance to cisplatin, carboplatin, doxorubicin, rucaparib, veliparib and AZD2461. ABCB1 expression was assessed by qRT-PCR, copy number, western blotting and immunohistochemical analysis and ABCB1 activity assessed by the Vybrant and P-glycoprotein-Glo assays. RESULTS: Paclitaxel-resistant cells were cross-resistant to olaparib, doxorubicin and rucaparib but not to veliparib or AZD2461. Resistance correlated with increased ABCB1 expression and was reversible following treatment with the ABCB1 inhibitors verapamil and elacridar. Active efflux of paclitaxel, olaparib, doxorubicin and rucaparib was confirmed in drug-resistant cells and in ABCB1-expressing bacterial membranes. CONCLUSIONS: We describe a common ABCB1-mediated mechanism of paclitaxel and olaparib resistance in ovarian cancer cells. Optimal choice of PARP inhibitor may therefore limit the progression of drug-resistant disease, while routine prescription of first-line paclitaxel may significantly limit subsequent chemotherapy options in ovarian cancer patients

Temporal evolution of solar energetic particle spectra

During solar flares and coronal mass ejections, solar energetic par- ticles (SEPs) may be released into the interplanetary medium and near-Earth locations. The energy spectra of SEP events at 1 AU are typically averaged over the entire event or studied in a few snapshots. In this paper we analyze the time evolution of the energy spectra of four large selected SEP events using a large number of snapshots. We use a multi-spacecraft and multi-instrument approach for the observations, obtained over a wide SEP energy range. We find large differences in the spectra at the beginning of the events as measured by different instruments. We show that over time, a wave-like structure is observed traveling through the spectra from the highest energies to the lowest energies, creating an “arch” shape which then straightens into a power law later in the event, after times of the order of 10 hours. We discuss the processes that determine SEP intensities and their role in shaping the spectral time evolution