Determination of Spontaneous Mutation Frequencies in Measles Virus under Nonselective Conditions

There is a paradox between the remarkable genetic stability of measles virus (MV) in the field and the high mutation rates implied by the frequency of the appearance of monoclonal antibody escape mutants generated when the virus is pressured to revert in vitro (S. J. Schrag, P. A. Rota, and W. J. Bellini, J. Virol. 73: 51-54, 1999). We established a highly sensitive assay to determine frequencies of various categories of mutations in large populations of wild-type and laboratory-adapted MVs using recombinant viruses containing an additional transcription unit (ATU) encoding enhanced green fluorescent protein (EGFP). Single and double mutations were made in the fluorophore of EGFP to ablate fluorescence. The frequencies of reversion mutants in the population were determined by measuring the appearance of fluorescence indicating a revertant virus. This allows mutation rates to be measured under nonselective conditions, as phenotypic reversion to fluorescence requires only either a single-or a double-nucleotide change and amino acid substitution, which does not affect the length of the nonessential reporter protein expressed from the ATU. Mutation rates in MV are the same for wild-type and laboratory-adapted viruses, and they are an order of magnitude lower than the previous measurement assessed under selective conditions. The actual mutation rate for MV is approximately 1.8 x 10(-6) per base per replication event. Copyright © 2013, American Society for Microbiology. All Rights Reserved.

Physical and numerical constraints in source modeling for finite difference simulation of room acoustics

In finite difference time domain simulation of room acoustics, source functions are subject to various constraints. These depend on the way sources are injected into the grid and on the chosen parameters of the numerical scheme being used. This paper addresses the issue of selecting and designing sources for finite difference simulation, by first reviewing associated aims and constraints, and evaluating existing source models against these criteria. The process of exciting a model is generalized by introducing a system of three cascaded filters, respectively, characterizing the driving pulse, the source mechanics, and the injection of the resulting source function into the grid. It is shown that hard, soft, and transparent sources can be seen as special cases within this unified approach. Starting from the mechanics of a small pulsating sphere, a parametric source model is formulated by specifying suitable filters. This physically constrained source model is numerically consistent, does not scatter incoming waves, and is free from zero- and low-frequency artifacts. Simulation results are employed for comparison with existing source formulations in terms of meeting the spectral and temporal requirements on the outward propagating wave.

Auditory gist: Recognition of very short sounds from timbre cues

Sounds such as the voice or musical instruments can be recognized on the basis of timbre alone. Here, sound recognition was investigated with severely reduced timbre cues. Short snippets of naturally recorded sounds were extracted from a large corpus. Listeners were asked to report a target category (e.g., sung voices) among other sounds (e.g., musical instruments). All sound categories covered the same pitch range, so the task had to be solved on timbre cues alone. The minimum duration for which performance was above chance was found to be short, on the order of a few milliseconds, with the best performance for voice targets. Performance was independent of pitch and was maintained when stimuli contained less than a full waveform cycle. Recognition was not generally better when the sound snippets were time-aligned with the sound onset compared to when they were extracted with a random starting time. Finally, performance did not depend on feedback or training, suggesting that the cues used by listeners in the artificial gating task were similar to those relevant for longer, more familiar sounds. The results show that timbre cues for sound recognition are available at a variety of time scales, including very short ones.

Deconstructing Victim and offender Identities in Discourses on Child Sexual Abuse: Hierarchies, Blame and the Good/Evil Dialectic

Contemporary social and political constructions of victimhood and offending behaviour lie at the heart of regulatory policies on child sexual abuse. Legislation is named after specific child victims of high profile cases, and a burgeoning range of pre-emptive measures are enacted to protect an amorphous class of ‘all potential victims’ from the risk sex offenders are seen as posing. Such policies are also heavily premised on the omnipresent predatory stranger. These constructed identities, however, are at odds with the actual identities of victims and offenders of such crimes. Drawing on a range of literatures, the core task of this article is to confront some of the complexities and tensions surrounding constructions of the victim/offender dyad within the specific context of sexual offending against children. In particular, the article argues that discourses on ‘blame’ – and the polarised notions of ‘innocence’ and ‘guilt’ – inform respective hierarchies of victimhood and offending concerning ‘legitimate’ victim and offender status. Based on these insights, the article argues for the need to move beyond such monochromatic understandings of victims and offenders of sexual crime and to reframe the politics of risk accordingly.

Temper outbursts in Prader-Willi syndrome: causes, behavioural and emotional sequence and responses by carers

Background: Temper outbursts are common in Prader-Willi syndrome but rarely described in detail. This study investigated the phenomenology of temper outbursts in terms of antecedents, sequence of behaviours and emotions and intervention strategies used.

Method: A semi-structured interview about temper outbursts was conducted with the main carers of seven children (9.5 to 16.7 years) and seven adults (24.7 to 47.10 years) with Prader-Willi syndrome (10 male, 4 female). Reliability and validity of the interview results was established.

Results: Various setting events increased and reduced the likelihood of temper outbursts. The most common antecedent was a change to routine or expectation. There were marked similarities in the sequence of behaviours and emotions during temper outbursts, with anger rising quickly followed by expressions of remorse and distress at the end of an outburst.

Discussion: The sequence of behaviours and emotions within outbursts was similar to that described in temper tantrums in typical development. Cognitive and emotional processes are likely to be important in the understanding of temper outbursts with implications for early intervention.

Attention-based modulation of tactile stimuli: A comparison between prefrontal lesion patients and healthy age-matched controls

Objectives: To investigate the role of the prefrontal cortex in attention-based modulation of cortical somatosensory processing.

Methods: Six prefrontal stroke patients were compared with eleven neurologically intact older adults during a vibrotactile discrimination task. All subjects attended to stimuli on one digit while ignoring distracter stimuli on a separate digit of the same hand. Subjects were required to report infrequent targets on the attended digit only. Throughout testing electroencephalography was used to measure event-related potentials for both task-relevant and irrelevant stimuli.

Results: Prefrontal patients demonstrated significant changes in cortical somatosensory processing based on attention compared to age-matched controls. This was evident both in early unimodal somatosensory processing (i.e. P100) and in later cortical processing stages (i.e. long-latency positivity). Moreover, there was a tendency towards a tonic loss of inhibition over early somatosensory cortical processing (i.e. P50).

Conclusions: The attention-based modulation noted for neurologically intact older adults was absent in prefrontal lesion patients.

Significance: The present study highlights the important role of prefrontal regions in sustaining inhibition over early sensory cortical processing stages and in modifying somatosensory transmission based on task-relevance. Notably these deficits extend beyond those previously shown to occur as a function of age.

Childhood trauma and the risk of violence in adulthood in a population with a psychotic illness.

There are strong links between childhood trauma and the risk of violence (Ford et al., 2007). Despite evidence that people with psychotic disorders are at a higher risk of violence than the general population (Witt et al., 2013) there have been few studies that have examined the trauma-violence link in this population (Spidel et al., 2010). This study explored the association between a history of childhood trauma (abuse, neglect and conflict-related trauma) and the risk of violence in adults with psychotic disorders. The strongest associations with the risk of violence were found for sexual abuse (r = .32, p < .05) and the impact of community conflict (r = .32, p < .05). An accumulative effect of trauma was found using a hierarchical regression (adjusted R2 = .14, F(2,37) = 4.23, p < .05). There are implications for applying models of violence to psychosis, risk assessment and treatment of people with psychotic disorders as well as informing trauma models and protective factors for children in conflict-affected regions.

Directional modulation transmitter radiation pattern considerations

A pattern synthesis approach is applied to a directional modulation (DM) system. A systematic synthesis procedure is suggested which ensures optimal constellation patterns production along pre-specified communication directions, whereas simultaneously conserving energy dispersal in other directions. In this study, the properties of DM systems synthesised from Gaussian magnitude far-field radiation pattern templates are used to illustrate performance benefits with regards to DM bit error rate response compared with those achieved by a conventional steered array.

Modelling lay-up automation and production rate interaction on the cost of large stiffened panel components

This paper presents an integrated design and costing method for large stiffened panels for the purpose of investigating the influence and interaction of lay-up technology and production rate on manufacturing cost. A series of wing cover panels (≈586kg, 19·9m2) have been sized with realistic requirements considering manual and automated lay-up routes. The integrated method has enabled the quantification of component unit cost sensitivity to changes in annual production rate and employed equipment maximum deposition rate. Moreover the results demonstrate the interconnected relationship between lay-up process and panel design, and unit cost. The optimum unit cost solution when using automated lay-up is a combination of the minimum deposition rate and minimum number of lay-up machines to meet the required production rate. However, the location of the optimum unit cost, at the boundaries between the number of lay-up machines required, can make unit cost very sensitive to small changes in component design, production rate, and equipment maximum deposition rate. - See more at: http://aerosociety.com/News/Publications/Aero-Journal/Online/1941/Modelling-layup-automation-and-production-rate-interaction-on-the-cost-of-large-stiffened-panel-components#sthash.0fLuu9iG.dpuf

Putrescine Reduces Antibiotic-Induced Oxidative Stress as a Mechanism of Modulation of Antibiotic Resistance in Burkholderia cenocepacia

Communication of antibiotic resistance among bacteria via small molecules is implicated in transient reduction of bacterial susceptibility to antibiotics, which could lead to therapeutic failures aggravating the problem of antibiotic resistance. Released putrescine from the extremely antibiotic resistant bacterium Burkholderia cenocepacia protects less resistant cells from different species against the antimicrobial peptide polymyxin B (PmB). Exposure of B. cenocepacia to sub-lethal concentrations of PmB and other bactericidal antibiotics induce reactive oxygen species (ROS) production and expression of the oxidative stress response regulator OxyR. We evaluated whether putrescine alleviates antibiotic-induced oxidative stress. The accumulation of intracellular ROS such as superoxide ion and hydrogen peroxide was assessed fluorometrically with dichlorofluorescein diacetate, while the expression of OxyR and putrescine synthesis enzymes was determined in luciferase assays using chromosomal promoter-lux reporter system fusions. We evaluated wild type and isogenic deletion mutant strains with defects in putrescine biosynthesis after exposure to sub-lethal concentrations of PmB and other bactericidal antibiotics. Exogenous putrescine protected against oxidative stress induced by PmB and other antibiotics, whereas reduced putrescine synthesis resulted in increased ROS generation, and a parallel increased sensitivity to PmB. Of the 3 B. cenocepacia putrescine synthesizing enzymes, PmB induced only BCAL2641, an ornithine decarboxylase. This study exposes BCAL2641 as a critical component of the putrescine-mediated communication of antibiotic resistance, and as a plausible target for designing inhibitors that would block the communication of such resistance among different bacteria, ultimately reducing the window of therapeutic failure in treating bacterial infections.

Propionibacterium acnes and Staphylococcus lugdunensis Cause Pyogenic Osteomyelitis in an Intramedullary Nail Model in Rabbits

Propionibacterium acnes and coagulase-negative staphylococci (CoNS) are opportunistic pathogens implicated in prosthetic joint and fracture fixation device-related infections. The purpose of this study was to determine whether P. acnes and the CoNS species Staphylococcus lugdunensis, isolated from an "aseptically failed" prosthetic hip joint and a united intramedullary nail-fixed tibial fracture, respectively, could cause osteomyelitis in an established implant-related osteomyelitis model in rabbits in the absence of wear debris from the implant material. The histological features of P. acnes infection in the in vivo rabbit model were consistent with localized pyogenic osteomyelitis, and a biofilm was present on all explanted intramedullary (IM) nails. The animals displayed no outward signs of infection, such as swelling, lameness, weight loss, or elevated white blood cell count. In contrast, infection with S. lugdunensis resulted in histological features consistent with both pyogenic osteomyelitis and septic arthritis, and all S. lugdunensis-infected animals displayed weight loss and an elevated white blood cell count despite biofilm detection in only two out of six rabbits. The differences in the histological and bacteriological profiles of the two species in this rabbit model of infection are reflective of their different clinical presentations: low-grade infection in the case of P. acnes and acute infection for S. lugdunensis. These results are especially important in light of the growing recognition of chronic P. acnes biofilm infections in prosthetic joint failure and nonunion of fracture fixations, which may be currently reported as "aseptic" failure. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Unpacking the Roma Participation Puzzle: Presence, Voice and Influence

The idea that Roma communities need to be included in public life is rather uncontroversial, widely accepted by Roma activists, academics and policy-makers in national and transnational political contexts. But, what do we mean by participation? Are we talking about formal political structures or do we refer to the capacity of ordinary Roma to have a presence in public life? The right to participation for minorities is specified by international norms but is interpreted differently in national contexts. Nevertheless, participation alone is not enough, thus minorities require 'effective' participation given that the utilitarian principles of liberal democracy means that groups such as Roma will always be outvoted. This article is based on the conviction that addressing the multiple and inter-connected issues facing Roma communities across Europe requires the participation of Roma in social, economic and political life. Whilst the article acknowledges the structural barriers which inhibit attempts to foster the integration of Roma communities, it does consider different conceptions of political participation including presence, voice and influence and how these are understood by the European Union and its member states with regards to Roma.