Development of sensors and non-destructive techniques to determine the performance of coatings in construction

The primary objective of this work was to examine and develop techniques for monitoring the degradation of Organically Coated Steel (OCS) in-situ. This included the detection of changes associated with the weathering to both the organic coating and metallic substrate. Initially, a review of current promising techniques was carried out however many were found to be unsuitable for this application and the adaptation of current techniques and the development of new techniques was considered. A brief concept investigation, based on initial testing and considerations, was used to determine a number of sensing techniques to examine. These included embedded, Resonant Frequency Identification (RFID), Magnetic Flux Leakage (MFL) and dielectric sensing. Each of these techniques were assessed for the application, prototyped, and tested against a range of samples to determine the accuracy and sensitivity of degradation detection provided. A range of poorly and highly durable coated samples were used in conjunction with accelerated weathering testing for this aim. Track based electronic printed sensors were presented as both a cut edge corrosion tracking and coating capacitance measurement method. While suffering somewhat from electrical paint compatibility issues both concepts showed merit in initial trials however the capacitive sensor ultimately proved insufficiently responsive to coating changes. The embedded, progressive failure-based, cut edge corrosion sensor was produced and tested in modern coating systems with moderate success. Novel applications of RFID and MLF techniques were considered and proved capable of detecting large changes in substrate condition due to significant corrosion. However, there was a lack of sufficient sensitivity when considering early-stage corrosion of durable modern OCS products. Finally, it was shown that a chipless antenna could be designed and optimised for novelly monitoring the changes to the dielectric properties of a paint layer due to degradation. However, ultimately this test, due to equipment requirements, lent itself more to lab testing than in-situ. Due to some of these limitations a different approach was considered in which the environmental factors influencing degradation were examined with the aim of relating these to performance across a building. It was observed that a combination of high humidity and the build-up of aggressive natural deposits contributed to high degradation rates in sheltered regions, such as building eaves, where microclimates were created. The build-up of deposits and their effect was presented as a key degradation accelerant during in-use service. A unique numerical simulation approach was developed to predict the natural washing, via rain impact and characteristics of the building analysed. This approach showed promise for determining areas unlikely to be naturally washed, and therefore subjected to a degradation accelerating, build-up of deposits. Given these understandings coated wetness sensors were considered as a realistic live-monitoring device capable of determining deposit build up and ultimately OCS lifetime

Transglutaminase 2 interacts with syndecan-4 and CD44 at the surface of human macrophages to promote removal of apoptotic cells

Tissue transglutaminase (TG2) is a multifunctional protein cross-linking enzyme that has been implicated in apoptotic cell clearance but is also important in many other cell functions including cell adhesion, migration and monocyte to macrophage differentiation. Cell surface-associated TG2 regulates cell adhesion and migration, via its association with receptors such as syndecan-4 and β1 and β3 integrins. Whilst defective apoptotic cell clearance has been described in TG2-deficient mice, the precise role of TG2 in apoptotic cell clearance remains ill-defined. Our work addresses the role of macrophage extracellular TG2 in apoptotic cell corpse clearance. Here we reveal TG2 expression and activity (cytosolic and cell surface) in human macrophages and demonstrate that inhibitors of protein crosslinking activity reduce macrophage clearance of dying cells. We show also that cell-impermeable TG2 inhibitors significantly inhibit the ability of macrophages to migrate and clear apoptotic cells through reduced macrophage recruitment to, and binding of, apoptotic cells. Association studies reveal TG2-syndecan-4 interaction through heparan sulphate side chains, and knockdown of syndecan-4 reduces cell surface TG2 activity and apoptotic cell clearance. Furthermore, inhibition of TG2 activity reduces crosslinking of CD44, reported to augment AC clearance. Thus our data define a role for TG2 activity at the surface of human macrophages in multiple stages of AC clearance and we propose that TG2, in association with heparan sulphates, may exert its effect on AC clearance via a mechanism involving the crosslinking of CD44

Human Influenza A (H5N1) Cases, Urban Areas of People’s Republic of China, 2005–2006

We investigated potential sources of infection for 6 confirmed influenza A (H5N1) patients who resided in urban areas of People’s Republic of China. None had known exposure to sick poultry or poultry that died from illness, but all had visited wet poultry markets before illness

Constitutive apoptosis in equine peripheral blood neutrophils in vitro

AbstractThe aim of this study was to characterise constitutive apoptosis in equine peripheral blood neutrophils, including assessment of factors that potentially modulate neutrophil survival through alteration of the rate of constitutive apoptosis. Cells underwent spontaneous time-dependent constitutive apoptosis when aged in culture for up to 36 h, developing the structural and functional features of apoptosis observed in many cell types, including human neutrophils. Neutrophils undergoing apoptosis also had diminished zymosan activated serum (ZAS)-stimulated chemiluminescence, but maintained responsiveness to phorbol myristate acetate (PMA). The constitutive rate of equine neutrophil apoptosis was promoted by lipopolysaccharide (LPS), tumour necrosis factor α and phagocytosis of opsonised ovine erythrocytes, while it was inhibited by dexamethasone and ZAS (a source of C5a). Formyl-Met-Leu-Phe, leukotriene B4, platelet activating factor and PMA had no demonstrable effect on equine neutrophil apoptosis. There was a difference between equine and human neutrophil apoptosis in response to LPS and the time-dependence of the response to dexamethasone

A Potential New Pathway for Staphylococcus aureus Dissemination: The Silent Survival of S. aureus Phagocytosed by Human Monocyte-Derived Macrophages

Although considered to be an extracellular pathogen, Staphylococcus aureus is able to invade a variety of mammalian, non-professional phagocytes and can also survive engulfment by professional phagocytes such as neutrophils and monocytes. In both of these cell types S. aureus promptly escapes from the endosomes/phagosomes and proliferates within the cytoplasm, which quickly leads to host cell death. In this report we show that S. aureus interacted with human monocyte-derived macrophages in a very different way to those of other mammalian cells. Upon phagocytosis by macrophages, S. aureus persisted intracellularly in vacuoles for 3–4 days before escaping into the cytoplasm and causing host cell lysis. Until the point of host cell lysis the infected macrophages showed no signs of apoptosis or necrosis and were functional. They were able to eliminate intracellular staphylococci if prestimulated with interferon-γ at concentrations equivalent to human therapeutic doses. S. aureus survival was dependent on the alternative sigma factor B as well as the global regulator agr, but not SarA. Furthermore, isogenic mutants deficient in α-toxin, the metalloprotease aureolysin, protein A, and sortase A were efficiently killed by macrophages upon phagocytosis, although with different kinetics. In particular α-toxin was a key effector molecule that was essential for S. aureus intracellular survival in macrophages. Together, our data indicate that the ability of S. aureus to survive phagocytosis by macrophages is determined by multiple virulence factors in a way that differs considerably from its interactions with other cell types. S. aureus persists inside macrophages for several days without affecting the viability of these mobile cells which may serve as vehicles for the dissemination of infection

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Improving Risk Models for Avian Influenza: The Role of Intensive Poultry Farming and Flooded Land during the 2004 Thailand Epidemic.

Since 1996 when Highly Pathogenic Avian Influenza type H5N1 first emerged in southern China, numerous studies sought risk factors and produced risk maps based on environmental and anthropogenic predictors. However little attention has been paid to the link between the level of intensification of poultry production and the risk of outbreak. This study revised H5N1 risk mapping in Central and Western Thailand during the second wave of the 2004 epidemic. Production structure was quantified using a disaggregation methodology based on the number of poultry per holding. Population densities of extensively- and intensively-raised ducks and chickens were derived both at the sub-district and at the village levels. LandSat images were used to derive another previously neglected potential predictor of HPAI H5N1 risk: the proportion of water in the landscape resulting from floods. We used Monte Carlo simulation of Boosted Regression Trees models of predictor variables to characterize the risk of HPAI H5N1. Maps of mean risk and uncertainty were derived both at the sub-district and the village levels. The overall accuracy of Boosted Regression Trees models was comparable to that of logistic regression approaches. The proportion of area flooded made the highest contribution to predicting the risk of outbreak, followed by the densities of intensively-raised ducks, extensively-raised ducks and human population. Our results showed that as little as 15% of flooded land in villages is sufficient to reach the maximum level of risk associated with this variable. The spatial pattern of predicted risk is similar to previous work: areas at risk are mainly located along the flood plain of the Chao Phraya river and to the south-east of Bangkok. Using high-resolution village-level poultry census data, rather than sub-district data, the spatial accuracy of predictions was enhanced to highlight local variations in risk. Such maps provide useful information to guide intervention.Journal ArticleSCOPUS: ar.jinfo:eu-repo/semantics/publishe