2,765 research outputs found

    Synchrotron x-ray measurement and finite element analysis of residual strain in TIG welded aluminium alloy 2024

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    Residual strains have been measured in a tungsten inert gas (TIG) butt-welded 2024 aluminum alloy plate using synchrotron X-ray diffraction. Novel two-dimensional strain maps spanning the entire plate reveal steep gradients in residual stress and provide detailed validation data for finite element (FE) analysis. Two variants of a FE model have been used to predict the residual strain distributions, incorporating different levels of plate constraint. The model uses decoupled thermal and elastic- plastic mechanical analyses and successfully predicts the longitudinal and transverse residual strain field over the entire weld. For butt weld geometries, the degree of transverse constraint is shown to be a significant boundary condition, compared to simpler bead-on-plate analyses. The importance of transverse residual strains for detailed model validation is highlighted, together with the need for care in selecting the location for line scans. The residual stress is largest in the heat-affected zone (HAZ), being equal to the local postweld yield stress, though the strength increases subsequently by natural aging. In addition, a halving of the diffraction line width has been observed local to the weld, and this correlates with the microstructural changes in the region

    Microbiological swabs have no role in the management of acute pilonidal abscesses

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    Aims: Microbiological swabs are often taken at the time of surgery for the treatment of acute pilonidal abscesses. This audit assessed whether swabs play a role in the management of these patients. Methods: A retrospective audit of electronic records was undertaken over a 2-year period between 1st January 2012 and December 31st 2013. Variables measured included patient sex, episode index, swab results, antibiotic use and recurrences. Results: Over the 2-year period there were 182 operations for acute pilonidal abscesses. Microbiological swabs were taken in 151 cases (83%). The most common culture was anaerobe (36%) followed by no growth (19%) and skin flora (8%). In total, 114 reports (94%) were issued after the patient had been discharged. Post-operative antibiotics were prescribed in 15 cases (8%) and within this group 9 patients (60%) had no growth on swab results. There were 11 recurrences (6%) with no correlation between the initial swab results and recurrent swab results being observed. Conclusions: In this audit, swab results did not alter any patient's treatment and nearly all reports were issued after the patient had been discharged. Recurrent abscesses do not appear to be linked to initial swab results

    AZD1775 Induces Toxicity Through Double-Stranded DNA Breaks Independently of Chemotherapeutic Agents in p53-Mutated Colorectal Cancer Cells

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    AZD1775 is a small molecule WEE1 inhibitor used in combination with DNA-damaging agents to cause premature mitosis and cell death in p53-mutated cancer cells. Here we sought to determine the mechanism of action of AZD1775 in combination with chemotherapeutic agents in light of recent findings that AZD1775 can cause double-stranded DNA (DS-DNA) breaks. AZD1775 significantly improved the cytotoxicity of 5-FU in a p53-mutated colorectal cancer cell line (HT29 cells), decreasing the IC50 from 9.3 μM to 3.5 μM. Flow cytometry showed a significant increase in the mitotic marker pHH3 (3.4% vs. 56.2%) and DS-DNA break marker γH2AX (5.1% vs. 50.7%) for combination therapy compared to 5-FU alone. Combination therapy also increased the amount of caspase-3 dependent apoptosis compared to 5-FU alone (4% vs. 13%). The addition of exogenous nucleosides to combination therapy significantly rescued the increased DS-DNA breaks and caspase-3 dependent apoptosis almost to the levels of 5-FU monotherapy. In conclusion, AZD1775 enhances 5-FU cytotoxicity through increased DS-DNA breaks, not premature mitosis, in p53-mutated colorectal cancer cells. This finding is important for designers of future clinical trials when considering the optimal timing and duration of AZD1775 treatment

    Rethinking Indian monsoon rainfall prediction in the context of recent global warming

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    Prediction of Indian summer monsoon rainfall (ISMR) is at the heart of tropical climate prediction. Despite enormous progress having been made in predicting ISMR since 1886, the operational forecasts during recent decades (1989–2012) have little skill. Here we show, with both dynamical and physical–empirical models, that this recent failure is largely due to the models’ inability to capture new predictability sources emerging during recent global warming, that is, the development of the central-Pacific El Nino-Southern Oscillation (CP–ENSO), the rapid deepening of the Asian Low and the strengthening of North and South Pacific Highs during boreal spring. A physical–empirical model that captures these new predictors can produce an independent forecast skill of 0.51 for 1989–2012 and a 92-year retrospective forecast skill of 0.64 for 1921–2012. The recent low skills of the dynamical models are attributed to deficiencies in capturing the developing CP–ENSO and anomalous Asian Low. The results reveal a considerable gap between ISMR prediction skill and predictability

    Increased seawater temperature increases the abundance and alters the structure of natural Vibrio populations associated with the coral Pocillopora damicornis.

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    Rising seawater temperature associated with global climate change is a significant threat to coral health and is linked to increasing coral disease and pathogen-related bleaching events. We performed heat stress experiments with the coral Pocillopora damicornis, where temperature was increased to 31°C, consistent with the 2-3°C predicted increase in summer sea surface maxima. 16S rRNA amplicon sequencing revealed a large shift in the composition of the bacterial community at 31°C, with a notable increase in Vibrio, including known coral pathogens. To investigate the dynamics of the naturally occurring Vibrio community, we performed quantitative PCR targeting (i) the whole Vibrio community and (ii) the coral pathogen Vibrio coralliilyticus. At 31°C, Vibrio abundance increased by 2-3 orders of magnitude and V. coralliilyticus abundance increased by four orders of magnitude. Using a Vibrio-specific amplicon sequencing assay, we further demonstrated that the community composition shifted dramatically as a consequence of heat stress, with significant increases in the relative abundance of known coral pathogens. Our findings provide quantitative evidence that the abundance of potential coral pathogens increases within natural communities of coral-associated microbes as a consequence of rising seawater temperature and highlight the potential negative impacts of anthropogenic climate change on coral reef ecosystems
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