High Temperature Deformation Mechanisms in a DLD Nickel Superalloy

The realisation of employing Additive Layer Manufacturing (ALM) technologies to produce components in the aerospace industry is significantly increasing. This can be attributed to their ability to offer the near-net shape fabrication of fully dense components with a high potential for geometrical optimisation, all of which contribute to subsequent reductions in material wastage and component weight. However, the influence of this manufacturing route on the properties of aerospace alloys must first be fully understood before being actively applied in-service. Specimens from the nickel superalloy C263 have been manufactured using Powder Bed Direct Laser Deposition (PB-DLD), each with unique post-processing conditions. These variables include two build orientations, vertical and horizontal, and two different heat treatments. The effects of build orientation and post-process heat treatments on the materials’ mechanical properties have been assessed with the Small Punch Tensile (SPT) test technique, a practical test method given the limited availability of PB-DLD consolidated material. SPT testing was also conducted on a cast C263 variant to compare with PB-DLD derivatives. At both room and elevated temperature conditions, differences in mechanical performances arose between each material variant. This was found to be instigated by microstructural variations exposed through microscopic and Energy Dispersive X-ray Spectroscopy (EDS) analysis. SPT results were also compared with available uniaxial tensile data in terms of SPT peak and yield load against uniaxial ultimate tensile and yield strength

Proposed revision of the higher tier testing requirements for EPPO Standard PP1/170: Test methods for evaluating the side-effects of plant protection products on honeybees

contribution to session I  Regulatory issues Background: Regulatory evaluations for the effects of pesticides on honeybees in the EU are based on the honeybee test guidelines and risk assessment scheme of the European Plant Protection Organisation (EPPO). While this is considered to be robust and effective, it is also recognised that a continuous process of review and appropriate development is necessary. A working group of the International Commission for Plant-Bee Relationships (ICPBR) had been set up to review the current guidance set out in the EPPO PP1/170 standard for higher tier testing i.e. semi-field (cage) test and full field studies. The aim of this group was to utilise the considerable experience obtained with honey bee testing. This paper presents the working group’s proposed revision to the EPPO standard PP1/170, taking into account feedback received from the 10th ICPBR Symposium in Bucharest.Results: The primary aim of the group has been to produce guidance that is sufficiently detailed yet suitably flexible so that it enables tests to be conducted and evaluated without being too prescriptive. In particular, it recognises that higher tier testing may arise as a result of various initial concerns e.g. adult toxicity, brood effects and systemic toxicity. The guidance is designed to provide the different emphasis that is required to meet the specific requirements of individual studies. Conclusion: The revision of higher tier testing for honeybees presented in this paper is proposed as an update to the current EPPO PP1/170 standard.Keywords: honey bees, test guidelines, higher tier, semi-field (cage) tests, field tests

Explanting Is an Ex Vivo Model of Renal Epithelial-Mesenchymal Transition

Recognised by their de novo expression of alpha-smooth muscle actin (SMA), recruitment of myofibroblasts is key to the pathogenesis of fibrosis in chronic kidney disease. Increasingly, we realise that epithelial-mesenchymal transition (EMT) may be an important source of these cells. In this study we describe a novel model of renal EMT. Rat kidney explants were finely diced on gelatin-coated Petri dishes and cultured in serum-supplemented media. Morphology and immunocytochemistry were used to identify mesenchymal (vimentin+, α-smooth muscle actin (SMA)+, desmin+), epithelial (cytokeratin+), and endothelial (RECA+) cells at various time points. Cell outgrowths were all epithelial in origin (cytokeratin+) at day 3. By day 10, 50 ± 12% (mean ± SE) of cytokeratin+ cells double-labelled for SMA, indicating EMT. Lectin staining established a proximal tubule origin. By day 17, cultures consisted only of myofibroblasts (SMA+/cytokeratin−). Explanting is a reproducible ex vivo model of EMT. The ability to modify this change in phenotype provides a useful tool to study the regulation and mechanisms of renal tubulointerstitial fibrosis

Exploring the therapeutic affordances of self-harm online support communities: an online survey of members

Background: A growing number of online communities have been established to support those who self-harm. However, little is known about the therapeutic affordances arising from engagement with these communities and resulting outcomes. Objective: The aim of this study was to explore the presence of therapeutic affordances as reported by members of self-harm online support communities. Methods: In total, 94 respondents (aged 13-63 years, mean=23.5 years; 94% female) completed an online survey exploring their experiences of engaging with a self-harm online support community. Respondents varied in terms of how long they had been accessing an online community, with 22% (21/94) accessing less than 1 year, 39% (37/94) 1 to 2 years, 14% (13/94) 2 to 3 years, and 24.5% (23/94) more than 3 years. Responses were analyzed using deductive thematic analysis. Results: The results of our analysis describe each of the five therapeutic affordances that were present in the data, namely (1) connection, the ability to make contact with others who self-harm for the purposes of mutual support and in so doing reduce feelings of loneliness and isolation; (2) adaptation, that is, how use of online support varies in relation to the personal circumstances of the individual user; (3) exploration, that is, the ability to learn about self-harm and learn about strategies to reduce or stop self-harming behavior; (4) narration, that is, the ability to share experiences, as well as read about the experiences of others; and (5) self-presentation, that is, how and what users present about themselves to others in the online community. Conclusions: Our findings suggest that engagement with self-harm online support communities may confer a range of therapeutic benefits for some users, which may serve to minimize the psychosocial burden of self-harm and promote positive coping strategies. In addition, the online nature of the support available may be helpful to those who are unable to access face-to-face support

The Snf2 Homolog Fun30 acts as a homodimeric ATP-dependent chromatin-remodeling enzyme

The Saccharomyces cerevisiae Fun30 (Function unknown now 30) protein shares homology with an extended family of Snf2-related ATPases. Here we report the purification of Fun30 principally as a homodimer with a molecular mass of about 250 kDa. Biochemical characterization of this complex reveals that it has ATPase activity stimulated by both DNA and chromatin. Consistent with this, it also binds to both DNA and chromatin. The Fun30 complex also exhibits activity in ATP-dependent chromatin remodeling assays. Interestingly, its activity in histone dimer exchange is high relative to the ability to reposition nucleosomes. Fun30 also possesses a weakly conserved CUE motif suggesting that it may interact specifically with ubiquitinylated proteins. However, in vitro Fun30 was found to have no specificity in its interaction with ubiquitinylated histones

Comparison of Different Phenotypic Approaches to Screen and Detect mecC-Harboring Methicillin-Resistant Staphylococcus aureus

Similar to mecA, mecC confers resistance against beta-lactams, leading to the phenotype of methicillin-resistant Staphylococcus aureus (MRSA). However, mecC-harboring MRSA strains pose special difficulties in their detection. The aim of this study was to assess and compare different phenotypic systems for screening, identification, and susceptibility testing of mecC-positive MRSA isolates. A well-characterized collection of mecC-positive S. aureus isolates (n 111) was used for evaluation. Routinely used approaches were studied to determine their suitability to correctly identify mecC-harboring MRSA, including three (semi)automated antimicrobial susceptibility testing (AST) systems and five selective chromogenic agar plates. Additionally, a cefoxitin disk diffusion test and an oxacillin broth microdilution assay were examined. All mecC-harboring MRSA isolates were able to grow on all chromogenic MRSA screening plates tested. Detection of these isolates in AST systems based on cefoxitin and/or oxacillin testing yielded overall positive agreements with the mecC genotype of 97.3% (MicroScan WalkAway; Siemens), 91.9% (Vitek 2; bioMérieux), and 64.9% (Phoenix, BD). The phenotypic resistance pattern most frequently observed by AST devices was “cefoxitin resistance/oxacillin susceptibility,” ranging from 54.1% (Phoenix) and 83.8% (Vitek 2) to 92.8% (WalkAway). The cefoxitin disk diffusion and oxacillin broth microdilution assays categorized 100% and 61.3% of isolates to be MRSA, respectively. The chromogenic media tested confirmed their suitability to reliably screen for mecC-harboring MRSA. The AST systems showed false-negative results with varying numbers, misidentifying mecC-harboring MRSA as methicillin-susceptible S. aureus. This study underlines cefoxitin’s status as the superior surrogate mecC-positive MRSA marker.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Giant planet formation in radially structured protoplanetary discs

This article has been accepted for publication in MNRAS ©: 2016: The authors. Published by Oxford University Press on behalf of the Royal Astronomical Society. All rights reserved.We acknowledge the comments received from an anonymous referee, which helped to improve the quality of this paper. GALC acknowledges the support of an STFC PhD studentship. This research utilised Queen Mary’s MidPlus computational facilities, supported by QMUL Research-IT and funded by EPSRC grant EP/K000128/

Biallelic Variants in TTLL5, Encoding a Tubulin Glutamylase, Cause Retinal Dystrophy

In a subset of inherited retinal degenerations (including cone, cone-rod, and macular dystrophies), cone photoreceptors are more severely affected than rods; ABCA4 mutations are the most common cause of this heterogeneous class of disorders. To identify retinal-disease-associated genes, we performed exome sequencing in 28 individuals with “cone-first” retinal disease and clinical features atypical for ABCA4 retinopathy. We then conducted a gene-based case-control association study with an internal exome data set as the control group. TTLL5, encoding a tubulin glutamylase, was highlighted as the most likely disease-associated gene; 2 of 28 affected subjects harbored presumed loss-of-function variants: c.[1586_1589delAGAG];[1586_1589delAGAG], p.[Glu529Valfs∗2];[Glu529Valfs∗2], and c.[401delT(;)3354G>A], p.[Leu134Argfs∗45(;)Trp1118∗]. We then inspected previously collected exome sequence data from individuals with related phenotypes and found two siblings with homozygous nonsense variant c.1627G>T (p.Glu543∗) in TTLL5. Subsequently, we tested a panel of 55 probands with retinal dystrophy for TTLL5 mutations; one proband had a homozygous missense change (c.1627G>A [p.Glu543Lys]). The retinal phenotype was highly similar in three of four families; the sibling pair had a more severe, early-onset disease. In human and murine retinae, TTLL5 localized to the centrioles at the base of the connecting cilium. TTLL5 has been previously reported to be essential for the correct function of sperm flagella in mice and play a role in polyglutamylation of primary cilia in vitro. Notably, genes involved in the polyglutamylation and deglutamylation of tubulin have been associated with photoreceptor degeneration in mice. The electrophysiological and fundus autofluorescence imaging presented here should facilitate the molecular diagnosis in further families

Weekend admission to hospital has a higher risk of death in the elective setting than in the emergency setting: a retrospective database study of national health service hospitals in England

<p>Abstract</p> <p>Background</p> <p>Although acute hospitals offer a twenty-four hour seven day a week service levels of staffing are lower over the weekends and some health care processes may be less readily available over the weekend. Whilst it is thought that emergency admission to hospital on the weekend is associated with an increased risk of death, the extent to which this applies to elective admissions is less well known. We investigated the risk of death in elective and elective patients admitted over the weekend versus the weekdays.</p> <p>Methods</p> <p>Retrospective statistical analysis of routinely collected acute hospital admissions in England, involving all patient discharges from all acute hospitals in England over a year (April 2008-March 2009), using a logistic regression model which adjusted for a range of patient case-mix variables, seasonality and admission over a weekend separately for elective and emergency (but excluding zero day stay emergency admissions discharged alive) admissions.</p> <p>Results</p> <p>Of the 1,535,267 elective admissions, 91.7% (1,407,705) were admitted on the weekday and 8.3% (127,562) were admitted on the weekend. The mortality following weekday admission was 0.52% (7,276/1,407,705) compared with 0.77% (986/127,562) following weekend admission. Of the 3,105,249 emergency admissions, 76.3% (2,369,316) were admitted on the weekday and 23.7% (735,933) were admitted on the weekend. The mortality following emergency weekday admission was 6.53% (154,761/2,369,316) compared to 7.06% (51,922/735,933) following weekend admission. After case-mix adjustment, weekend admissions were associated with an increased risk of death, especially in the elective setting (elective Odds Ratio: 1.32, 95% Confidence Interval 1.23 to 1.41); vs emergency Odds Ratio: 1.09, 95% Confidence Interval 1.05 to 1.13).</p> <p>Conclusions</p> <p>Weekend admission appears to be an independent risk factor for dying in hospital and this risk is more pronounced in the elective setting. Given the planned nature of elective admissions, as opposed to the unplanned nature of emergency admissions, it would seem less likely that this increased risk in the elective setting is attributable to unobserved patient risk factors. Further work to understand the relationship between weekend processes of care and mortality, especially in the elective setting, is required.</p