Clinical quantification of the integrin αvβ6 by [18F]FB-A20FMDV2 positron emission tomography in healthy and fibrotic human lung (PETAL Study)

© 2019, The Author(s). Purpose: The RGD-integrin, αvβ6, plays a role in the pathogenesis of pulmonary fibrosis through activation of transforming growth factor beta (TGFβ). This study sought to quantify expression of αvβ6 in the lungs of healthy humans and subjects with pulmonary fibrosis using the αvβ6-selective [18F]FB-A20FMDV2 PET ligand. Methods: [18F]FB-A20FMDV2 PET/CT scans were performed in healthy subjects and those with fibrotic lung disease. Standard uptake values (SUV) and volume of distribution (VT) were used to quantify αvβ6 expression. In subjects with fibrotic lung disease, qualitative assessment of the relationship between αvβ6 expression and the distribution of fibrosis on high resolution computed tomography was conducted. Results: A total of 15 participants (6 healthy, 7 with idiopathic pulmonary fibrosis (IPF) and 2 with connective tissue disease (CTD) associated PF) were enrolled. VT and SUV of [18F]FB-A20FMDV2 were increased in the lungs of subjects with pulmonary fibrosis (PF) compared with healthy subjects. Geometric mean VT (95% CI) was 0.88 (0.60, 1.29) mL/cm3 for healthy subjects, and 1.40 (1.22, 1.61) mL/cm3 for subjects with IPF; and SUV was 0.54 (0.36, 0.81) g/mL for healthy subjects and 1.03 (0.86, 1.22) g/mL for subjects with IPF. The IPF/healthy VT ratio (geometric mean, (95% CI of ratio)) was 1.59 (1.09, 2.32) (probability ratio > 1 = 0.988)) and the SUV ratio was 1.91 (1.27, 2.87) (probability ratio > 1 = 0.996). Increased uptake of [18F]FB-A20FMDV2 in PF was predominantly confined to fibrotic areas. [18F]FB-A20FMDV2 measurements were reproducible at an interval of 2 weeks. [18F]FB-A20FMDV2 was safe and well tolerated. Conclusions: Lung uptake of [18F]FB-A20FMDV2, a measure of expression of the integrin αvβ6, was markedly increased in subjects with PF compared with healthy subjects

Oxygen isotope transfer rates during the oxidative coupling of methane over a Li/MgO catalyst

The rates of various oxygen isotope transfer processes over Li/MgO catalysts have been investigated in a flow system under conditions relevant to methane coupling. Using ¹⁶O₂/¹⁸O₂ mixtures, mixing to form ¹⁶O₁₈O reached equilibrium at 700 and 750°C when helium was used as the carrier. The extent of equilibration was greatly reduced when the same mixture was used to oxidize methane. The inhibition occurs because mixing requires that the catalytic sites be in oxide form and these sites are converted to carbonate by the carbon dioxide formed from methane concurrently with ethane and ethylene. The same inhibition could be demonstrated directly when using an inert carrier by including C¹⁸O₂ in the feed. When C¹⁸O₂ was added during methane coupling with ¹⁶O₂ as the sole oxidant, there was complete equilibration between added C¹⁸O₂ and C¹⁶O₂ derived from methane. In addition some ¹⁸O was transferred into unreacted ¹⁶O₂. This exchange did not produce ¹⁶O₂, ¹⁶O₁₈O, and ¹⁸O₂ in equilibrium. There was a slight excess of ¹⁸O₂ due to the occurrence of some two-place exchange. Transient experiments in which C¹⁸O₂ alone was carried over Li/MgO showed that only a small fraction of the total oxygen pool of the catalyst participated in exchange. It is probably associated with lithium. When C¹⁸O was included in reacting CH₄/¹⁶O₂ mixtures, approximately one-half of it was oxidized to carbon dioxide. Some exchange of ¹⁸O out of unreacted C¹⁸O took place but the rate of this process was much slower than transfer from carbon dioxide to oxygen. Calculations indicate that the catalyst is able to carry out exchange reactions of oxygen molecules faster than it reacts oxygen with methane. Hence methane coupling is unlikely to be limited by the supply of oxygen to the catalyst surface when the Li/MgO system is used.13 page(s

Isotopic evidence for direct methyl coupling and ethane to ethylene conversion during partial oxidation of methane over Li/MgO

The products of the reaction of a CH₄/CD₄/O₂ mixture over a Li-promoted MgO (Li/MgO) catalyst at 750°C have been determined by mass spectrometry and high-resolution Fourier transform infrared spectroscopy. Under these conditions there was no significant hydrogen exchange between CH₄ and CD₄. C₂H₆, CD₃CH₃, and C₂D₆ were the only ethanes detected, and C₂H₄, CD₂CH₂, and C₂D₄ were the only ethylenes. The relative concentrations of the hydrocarbon products could be predicted on the basis of the relative concentrations of CH₃ and CD₃ determined by the kinetic isotope effect. The results suggest that the reaction proceeds almost exclusively by gas-phase methyl coupling and that ethylene is produced by gas-phase conversion of ethane.4 page(s

Measurements of kinetic isotope effects and hydrogen/deuterium distributions over methane oxidative coupling catalysts

The kinetic isotope effect for CH₄ compared to that for CD₄ has been measured for the oxidative coupling reaction of methane over LiMgO, SrCO₃, and Sm₂O₃ catalysts in a flow reactor. Each catalyst gave results consistent with C?H bond breaking being the slow step. For temperatures between 680-780°C over LiMgO, kHKD decreased slightly with temperature. The isotope effect for ethane production was more sensitive to the level of conversion and declined from 1.8 at low conversion to near unity under conditions where the ethylene to ethane ratio was high (~1). Selectivities to hydrocarbons were lower with CD₄ and did not change with decreased flow rates, implying that either COₓ and C₂ products arise by totally separate slow steps or, if a common step with CH3 radicals is involved, then COₓ formation occurs on the catalyst. Experiments with CH₄CD₄ mixtures showed that CH₃CD₃ and CH₂CD₂ were the dominant mixed products. The distribution of the ethanes always reflected the relative concentrations of CH3 and CD₃ determined by the kinetic isotope effect. At low ethylene to total C₂ ratios (~0.2) this was also true for ethylene; but at higher ratios substantial exchange to produce ethylenes other than C₂H₄, CH₂CD₂, and C₂D₄ occurred. The concentration of the exchanged methanes correlated with total methane conversion but was dependent on the surface. Exchange in the ethylenes also correlated with exchange in the methanes and purely gas phase processes appear at least partially responsible. H₂: HD: D₂ ratios are always at equilibrium and exchange also occurs between CD₄ and H₂.15 page(s

An atomic force microscopy study of weathering of polyester/melamine paint surfaces

The use of an atomic force microscope (AFM) for rapid assessment of the durability of exterior polyester/melamine paints has been investigated. The study established an AFM imaging technique that produces data representative of weathering rates of paint films under a range of weathering regimes of varying severity. The effect of scan size on the average roughness parameter was investigated, leading to the adoption of two specified scan sizes. It was further found that both TappingMode™ and contact mode imaging gave equivalent detail of surface topography for these samples. However, TappingMode™ gave a clearer representation of the pigment/binder composite structure. Importantly, a technique was developed which reduces sample to sample variability by allowing a specified area to be repeatedly imaged as a function of weathering time. The images collected were found to show important detail regarding the mechanism of weathering, and the role of binder stability and pigment loss

Multidisciplinary expertise applied to underground coal mining R and D projects with emphasis on adoption of lean automation techniques

Mining r&d at the University of Wollongong has concentrated on assisting the Industry by Developing new techniques enabling mining engineers to exploit the capabilities of other engineering and science disciplines and by assimilation and modifying technologies successfully used in other Industries

The rate controlling step In the oxidative coupling of methane over a lithium-promoted magnesium-oxide catalyst

The rate of conversion of CH₄ in the oxidative coupling reaction over a Li/MgO catalyst at 750°C is 1.5 times greater than that of CD₄ demonstrating that C–H bond breaking is the rate determining step in this reaction.3 page(s

Gene-expression patterns in whole blood identify subjects at risk for recurrent tuberculosis.

BACKGROUND: The majority of patients with tuberculosis who comply with appropriate treatment are cured. However, approximately 5% subsequently have a repeat disease episode, usually within 2 years of successful combination therapy. Presently, there is no way of predicting which patients will experience a relapse. METHODS: We identified 10 subjects who had previously experienced recurrent tuberculosis and carefully matched them to cured subjects who had had only 1 episode of tuberculosis, to patients with active tuberculosis, and to latently infected healthy subjects. We compared their ex vivo whole-blood gene-expression profiles by use of DNA array technology and confirmed the results by use of quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR). RESULTS: The 4 clinical tuberculosis groups exhibited distinct patterns of gene expression. The gene-transcript profiles of the patients with recurrent tuberculosis were more similar to those of the patients with active tuberculosis than to those of the cured or latently infected subjects. Discriminant analysis of a training data set showed that 9 genes were sufficient to classify the subjects. We confirmed that measurement of the expression of these genes by qRT-PCR can accurately discriminate between subjects in a test set of samples. CONCLUSIONS: A simple test based on gene-expression patterns may be used as a biomarker of cure while identifying patients who are at risk for relapse. This would facilitate the introduction of new tuberculosis drugs