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

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

Shape-dependent antibacterial effects of non-cytotoxic gold nanoparticles

Gold nanoparticles (AuNPs) of various shapes (including spheres, stars and flowers), with similar dimensions, were synthesized and evaluated for their antibacterial effects toward Staphylococcus aureus, a bacterium responsible for numerous life-threatening infections worldwide. Optical growth curve measurements and Gompertz modeling showed significant AuNP shape- and concentration-dependent decreases in bacterial growth with increases in bacterial growth lag time. To evaluate prospective use in in vivo systems, the cytotoxicity of the same AuNPs was evaluated toward human dermal fibroblasts in vitro by 3-(4,5 dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) viability assays and confocal microscopy. No indication of any mammalian cell toxicity or morphological effects was found. Additionally, it was observed that the AuNPs were readily internalized in fibroblasts after 4 days of incubation. Most importantly, the results of the present study showed that gold nanoflowers in particular possessed the most promising non-cytotoxic mammalian cell behavior with the greatest shape-dependent antibacterial activity-promising properties for their future investigation in a wide range of anti-infection applications

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

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

Moist convection and its upscale effects in simulations of the Indian monsoon with explicit and parametrised convection

In common with many global models, the Met Office Unified Model (MetUM) climate simulations show large errors in Indian summer monsoon rainfall, with a wet bias over the equatorial Indian Ocean, a dry bias over India, and with too weak low-level flow into India. The representation of moist convection is a dominant source of error in global models, where convection must be parametrised, with the errors growing quickly enough to affect both weather and climate simulations. Here we use the first multi- week continental-scale MetUM simulations over India, with grid-spacings that allow explicit convection, to examine how convective parametrisation contributes to model biases in the region. Some biases are improved in the convection-permitting simulations with more intense rainfall over India, a later peak in the diurnal cycle of convective rainfall over land, and a reduced positive rainfall bias over the Indian Ocean. The simulations suggest that the reduced rainfall over the Indian Ocean leads to an enhanced monsoon circulation and transport of moisture into India. Increases in latent heating associated with increased convection over land deepen the monsoon trough and enhance water vapour transport into the continent. In addition, delayed continental convection allows greater surface insolation and, along with the same rain falling in more intense bursts, generates a drier land surface. This increases land-sea temperature contrasts, and further enhances onshore flow. Changes in the low-level water vapour advection into India are dominated by these changes to the flow, rather than to the moisture content in the flow. The results demonstrate the need to improve the representations of convection over both land and oceans to improve simulations of the monsoon

A fresh look at preoperative body washing

National guidelines do not support preoperative body washing to reduce surgical site infections, instead recommending bathing or showering with soap. Yet preoperative body washing continues to be widely used in many hospitals across Europe. This paper suggests that existing trials of preoperative body washing, upon which guidelines are based, are dated and proposes a new investigation of preoperative body washing using modern definitions of surgical site infection with standardised patient follow up, modern surgical techniques and well designed trials. This paper provides a critique of existing guidelines and describes a randomised trial with 60 participants to compare the effect of soap and two antiseptic washing products on colony forming units (CFUs) for up to six hours. Chlorhexidine gluconate and octenidine were significantly more effective than soap in reducing CFUs in the underarm, and chlorhexidine was significantly more effective than soap in reducing CFUs in the groin

Investigation into Adaptation in Genes Associated with Response to Estrogenic Pollution in Populations of Roach (Rutilus rutilus) Living in English Rivers

UK Natural Environmental Research Council (NERC; NE/K004263/1); NERC Biomolecular Analysis Facility for funding (NBAF866); Medical Research Council Clinical Infrastructure award (MR/M008924/1); Wellcome Trust Institutional Strategic Support Fund (WT097835MF); Wellcome Trust Multi User Equipment Award (WT101650MA); BBSRC LOLA award (BB/ K003240/1)

A large-scale study of a poultry trading network in Bangladesh: implications for control and surveillance of avian influenza viruses

Since its first report in 2007, avian influenza (AI) has been endemic in Bangladesh. While live poultry marketing is widespread throughout the country and known to influence AI dissemination and persistence, trading patterns have not been described. The aim of this study is to assess poultry trading practices and features of the poultry trading networks which could promote AI spread, and their potential implications for disease control and surveillance. Data on poultry trading practices was collected from 849 poultry traders during a cross-sectional survey in 138 live bird markets (LBMs) across 17 different districts of Bangladesh. The quantity and origins of traded poultry were assessed for each poultry type in surveyed LBMs. The network of contacts between farms and LBMs resulting from commercial movements of live poultry was constructed to assess its connectivity and to identify the key premises influencing it

Hazard Analysis of Critical Control Points Assessment as a Tool to Respond to Emerging Infectious Disease Outbreaks

Highly pathogenic avian influenza virus (HPAI) strain H5N1 has had direct and indirect economic impacts arising from direct mortality and control programmes in over 50 countries reporting poultry outbreaks. HPAI H5N1 is now reported as the most widespread and expensive zoonotic disease recorded and continues to pose a global health threat. The aim of this research was to assess the potential of utilising Hazard Analysis of Critical Control Points (HACCP) assessments in providing a framework for a rapid response to emerging infectious disease outbreaks. This novel approach applies a scientific process, widely used in food production systems, to assess risks related to a specific emerging health threat within a known zoonotic disease hotspot. We conducted a HACCP assessment for HPAI viruses within Vietnam’s domestic poultry trade and relate our findings to the existing literature. Our HACCP assessment identified poultry flock isolation, transportation, slaughter, preparation and consumption as critical control points for Vietnam’s domestic poultry trade. Introduction of the preventative measures highlighted through this HACCP evaluation would reduce the risks posed by HPAI viruses and pressure on the national economy. We conclude that this HACCP assessment provides compelling evidence for the future potential that HACCP analyses could play in initiating a rapid response to emerging infectious diseases