Residual stresses in condition monitoring and repair of thermal power generation components

Residual stresses have a significant impact on fatigue and fracture of engineering components and structures, with an effect that is largely dependent on the sign of the residual stress relative to that of the applied stress, i.e. on whether they add to, or subtract from, the applied stress. The present paper will emphasise the importance of detailed knowledge of residual stresses to applications in thermal power generation. The context of the examples is condition monitoring and repair procedures where assessment of the influence of residual stress fields is important to both fatigue and fracture performance, and to certification of the repair procedure itself. The main conclusion in the paper is that the innovative use of solid-state friction taper hydro-pillar processes can offer additional capability in condition monitoring of through-thickness creep damage in thermal power plant, as well as provide cost-effective local repair of creep or fatigue damage in, for example, thick-walled steam pipe and blade-disc attachment holes

Time-of-Flight Spectroscopy of 252 Cf Spontaneous Fission Neutrons:Influences of Detector Voltage, Pulse-Shape Discrimination and Shielding

Experimental measurements to explore the effect of detector voltage, pulse-shape discrimination (PSD) threshold and detector shielding on time-of-flight measurements of the 252Cf neutron spectrum made with organic scintillation detectors are described. It is found that detector voltage has a major effect, whilst changing the PSD threshold and shielding the detectors to optimize sensitivity to the desired gamma-neutron correlation results in a small effect

Peak radial growth of diffuse-porous species occurs during periods of lower water availability than for ring-porous and coniferous trees

Climate models project warmer summer temperatures will increase the frequency and heat severity of droughts in temperate forests of Eastern North America. Hotter droughts are increasingly documented to affect tree growth and forest dynamics, with critical impacts on tree mortality, carbon sequestration and timber provision. The growing acknowledgement of the dominant role of drought timing on tree vulnerability to water deficit raises the issue of our limited understanding of radial growth phenology for most temperate tree species. Here, we use well-replicated dendrometer band data sampled frequently during the growing season to assess the growth phenology of 610 trees from 15 temperate species over 6 years. Patterns of diameter growth follow a typical logistic shape, with growth rates reaching a maximum in June, and then decreasing until process termination. On average, we find that diffuse-porous species take 16-18 days less than other wood-structure types to put on 50% of their annual diameter growth. However, their peak growth rate occurs almost a full month later than ring-porous and conifer species (ca. 24 +/- 4 days; mean +/- 95% credible interval). Unlike other species, the growth phenology of diffuse-porous species in our dataset is highly correlated with their spring foliar phenology. We also find that the later window of growth in diffuse-porous species, coinciding with peak evapotranspiration and lower water availability, exposes them to a higher water deficit of 88 +/- 19 mm (mean +/- SE) during their peak growth than ring-porous and coniferous species (15 +/- 35 mm and 30 +/- 30 mm, respectively). Given the high climatic sensitivity of wood formation, our findings highlight the importance of wood porosity as one predictor of species climatic sensitivity to the projected intensification of the drought regime in the coming decades.Peer reviewe

Recruitment of inflammatory monocytes by senescent fibroblasts inhibits antigen-specific tissue immunity during human aging

We have previously shown that healthy older adults exhibit reduced cutaneous immune responses during a varicella zoster virus (VZV) antigen challenge that correlated with a nonspecific inflammatory response to the injection itself. Here we found that needle damage during intradermal injections in older adults led to an increase in the number of cutaneous senescent fibroblasts expressing CCL2, resulting in the local recruitment of inflammatory monocytes. These infiltrating monocytes secreted prostaglandin E2, which inhibited resident memory T cell activation and proliferation. Pretreatment of older participants with a p38 mitogen-activated protein kinase inhibitor in vivo decreased CCL2 expression and inhibited monocyte recruitment and secretion of prostaglandin E2. This coincided with an increased response to VZV antigen challenge in the skin. Our results point to a series of molecular and cellular mechanisms that link cellular senescence, tissue damage, excessive inflammation and reduced immune responsiveness in human skin and demonstrate that tissue-specific immunity can be restored in older adults by short-term inhibition of inflammatory responses

The Characterization of Varicella Zoster Virus–Specific T Cells in Skin and Blood during Aging

Reactivation of the varicella zoster virus (VZV) increases during aging. Although the effects of VZV reactivation are observed in the skin (shingles), the number and functional capacity of cutaneous VZV-specific T cells have not been investigated. The numbers of circulating IFN-γ-secreting VZV-specific CD4+ T cells are significantly decreased in old subjects. However, other measures of VZV-specific CD4+ T cells, including proliferative capacity to VZV antigen stimulation and identification of VZV-specific CD4+ T cells with an major histocompatibility complex class II tetramer (epitope of IE-63 protein), were similar in both age groups. The majority of T cells in the skin of both age groups expressed CD69, a characteristic of skin-resident T cells. VZV-specific CD4+ T cells were significantly increased in the skin compared with the blood in young and old subjects, and their function was similar in both age groups. In contrast, the number of Foxp3+ regulatory T cells and expression of the inhibitory receptor programmed cell death -1 PD-1 on CD4+ T cells were significantly increased in the skin of older humans. Therefore, VZV-specific CD4+ T cells in the skin of older individuals are functionally competent. However, their activity may be restricted by multiple inhibitory influences in situ

The optimal second-line therapy for older adults with type 2 diabetes mellitus: protocol for a systematic review and network meta-analysis using individual participant data (IPD)

Background: Due to increasing life expectancy, almost half of people with type 2 diabetes are aged 65 years or over worldwide. When metformin alone does not control blood sugar, the choice of which second-line therapy to prescribe next is not clear from currently available evidence. The existence of frailty and comorbidities in older adults further increases the complexity of medical decision-making. As only a relatively small proportion of trials report results separately for older adults, the relative efficacy and safety of second-line therapies in older adults with type 2 diabetes mellitus are unknown and require further investigation. This individual participant data (IPD) network meta-analysis evaluates the relative efficacy and safety of second-line therapies on their own or in combination in older adults with type 2 diabetes mellitus. Methods: All relevant published and unpublished trials will be identified. Studies published prior to 2015 will be identified from two previous comprehensive aggregate data network meta-analyses. Searches will be conducted in CENTRAL, MEDLINE, and EMBASE from 1st January 2015 onwards, and in clinicaltrials.gov from inception. Randomised controlled trials with at least 100 estimated older adults (≥ 65 years) receiving at least 24 weeks of intervention that assess the effects of glucose-lowering drugs on mortality, glycemia, vascular and other comorbidities outcomes, and quality of life will be eligible. The screening and data extraction process will be conducted independently by two researchers. The quality of studies will be assessed using the Cochrane risk of bias tool 2. Anonymised IPD of all eligible trials will be requested via clinical trial portals or by contacting the principal investigators or sponsors. Received data will be reanalysed where necessary to standardise outcome metrics. Network meta-analyses will be performed to determine the relative effectiveness of therapies. Discussion: With the increasing number of older adults with type 2 diabetes worldwide, an IPD network meta-analysis using data from all eligible trials will provide new insights into the optimal choices of second-line antidiabetic drugs to improve patient management and reduce unnecessary adverse events and the subsequent risk of comorbidities in older adults. Systematic review registration: PROSPERO CRD42021272686

Transcriptional analysis of temporal gene expression in germinating Clostridium difficile 630 endospores.

Clostridium difficile is the leading cause of hospital acquired diarrhoea in industrialised countries. Under conditions that are not favourable for growth, the pathogen produces metabolically dormant endospores via asymmetric cell division. These are extremely resistant to both chemical and physical stress and provide the mechanism by which C. difficile can evade the potentially fatal consequences of exposure to heat, oxygen, alcohol, and certain disinfectants. Spores are the primary infective agent and must germinate to allow for vegetative cell growth and toxin production. While spore germination in Bacillus is well understood, little is known about C. difficile germination and outgrowth. Here we use genome-wide transcriptional analysis to elucidate the temporal gene expression patterns in C. difficile 630 endospore germination. We have optimized methods for large scale production and purification of spores. The germination characteristics of purified spores have been characterized and RNA extraction protocols have been optimized. Gene expression was highly dynamic during germination and outgrowth, and was found to involve a large number of genes. Using this genome-wide, microarray approach we have identified 511 genes that are significantly up- or down-regulated during C. difficile germination (p≤0.01). A number of functional groups of genes appeared to be co-regulated. These included transport, protein synthesis and secretion, motility and chemotaxis as well as cell wall biogenesis. These data give insight into how C. difficile re-establishes its metabolism, re-builds the basic structures of the vegetative cell and resumes growth

Impact of Zostavax Vaccination on T-Cell Accumulation and Cutaneous Gene Expression in the Skin of Older Humans After Varicella Zoster Virus Antigen-Specific Challenge

Background The live attenuated vaccine Zostavax was developed to prevent varicella zoster virus (VZV) reactivation that causes herpes zoster (shingles) in older humans. However, the impact of vaccination on the cutaneous response to VZV is not known. Methods We investigated the response to intradermal VZV antigen challenge before and after Zostavax vaccination in participants >70 years of age by immunohistological and transcriptomic analyses of skin biopsy specimens collected from the challenge site. Results Vaccination increased the proportion of VZV-specific CD4+ T cells in the blood and promoted the accumulation of both CD4+ and CD8+ T cells in the skin after VZV antigen challenge. However, Zostavax did not alter the proportion of resident memory T cells (CD4+ and CD8+) or CD4+Foxp3+ regulatory T cells in unchallenged skin. After vaccination, there was increased cutaneous T-cell proliferation at the challenge site and also increased recruitment of T cells from the blood, as indicated by an elevated T-cell migratory gene signature. CD8+ T-cell–associated functional genes were also highly induced in the skin after vaccination. Conclusion Zostavax vaccination does not alter the abundance of cutaneous resident memory T cells but instead increases the recruitment of VZV-specific T cells from the blood and enhances T-cell activation, particularly cells of the CD8+ subset, in the skin after VZV antigen challenge

Digital twin challenges and opportunities for nuclear fuel manufacturing applications

There have been a number of digital twin (DT) frameworks proposed for multiple disciplines in recent years. However, there is a need to develop systematic methodologies to improve our ability to produce DT solutions for the nuclear fuel industry considering specific requirements and conditions exclusive to the nuclear fuel manufacturing cycle. A methodology tailored for nuclear fuel production is presented in this paper. Due to the nature of the chemical processes involved in fuel manufacturing, we highlight the importance of using a combination of physics-based and data-driven modelling. We introduce key technologies for DT construction and the technical challenges for DT are discussed. Furthermore, we depict typical application scenarios, such as key stages of the nuclear manufacturing cycle. Finally, a number of technology issues and research questions related to DT and nuclear fuel manufacturing are identified

Digital twin challenges and opportunities for nuclear fuel manufacturing applications

There have been a number of digital twin (DT) frameworks proposed for multiple disciplines in recent years. However, there is a need to develop systematic methodologies to improve our ability to produce DT solutions for the nuclear fuel industry considering specific requirements and conditions exclusive to the nuclear fuel manufacturing cycle. A methodology tailored for nuclear fuel production is presented in this paper. Due to the nature of the chemical processes involved in fuel manufacturing, we highlight the importance of using a combination of physics-based and data-driven modelling. We introduce key technologies for DT construction and the technical challenges for DT are discussed. Furthermore, we depict typical application scenarios, such as key stages of the nuclear manufacturing cycle. Finally, a number of technology issues and research questions related to DT and nuclear fuel manufacturing are identified