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BACKGROUND AND PURPOSE: Chronic obstructive pulmonary disease (COPD) is a major cause of illness and death, often induced by cigarette smoking (CS). It is characterized by pulmonary inflammation and fibrosis that impairs lung function. Existing treatments aim to control symptoms but have low efficacy, and there are no broadly effective treatments. A new potential target is the ectoenzyme, semicarbazide-sensitive mono-amine oxidase (SSAO; also known as vascular adhesion protein-1). SSAO is elevated in smokers' serum and is a pro-inflammatory enzyme facilitating adhesion and transmigration of leukocytes from the vasculature to sites of inflammation. EXPERIMENTAL APPROACH: PXS-4728A was developed as a low MW inhibitor of SSAO. A model of COPD induced by CS in mice reproduces key aspects of human COPD, including chronic airway inflammation, fibrosis and impaired lung function. This model was used to assess suppression of SSAO activity and amelioration of inflammation and other characteristic features of COPD. KEY RESULTS: Treatment with PXS-4728A completely inhibited lung and systemic SSAO activity induced by acute and chronic CS-exposure. Daily oral treatment inhibited airway inflammation (immune cell influx and inflammatory factors) induced by acute CS-exposure. Therapeutic treatment during chronic CS-exposure, when the key features of experimental COPD develop and progress, substantially suppressed inflammatory cell influx and fibrosis in the airways and improved lung function. CONCLUSIONS AND IMPLICATIONS: Treatment with a low MW inhibitor of SSAO, PXS-4728A, suppressed airway inflammation and fibrosis and improved lung function in experimental COPD, demonstrating the therapeutic potential of PXS-4728A for this debilitating disease.

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The problem of the disagreement between cirrus crystal sizes determined remotely and by in situ measurements is shown to be due to inappropriate application of Mie theory. We retrieved the absorption optical depth at 8.3 and 11.1 mum from 11 tropical anvil cirrus clouds, using data from the High Resolution Infrared Radiation Sounder (HIRS). We related the absorption optical depth ratio between the two wavelengths to crystal size (the size was defined in terms of the crystal median mass dimension) by assuming Mie theory applied to ice spheres and anomalous diffraction theory (ADT) applied to hexagonal columns, hexagonal plates, bullet rosettes, and aggregates (polycrystals). The application of Mie theory to retrievals yielded crystal sizes approximately one third those obtained with ADT. The retrievals of crystal size by use of HIRS data are compared with measurements of habit and crystal size obtained from in situ measurements of tropical anvil cirrus particles. The results of the comparison show that ADT provides the more realistic retrieval. Moreover, we demonstrate that at infrared wavelengths retrieval of crystal size depends on assumed habit. The reason why Mie theory predicts smaller sizes than ADT is shown to result from particle geometry and enhanced absorption owing to the capture of photons from above the edge of the particle (tunneling). The contribution of particle geometry to absorption is three times greater than from tunneling, but this process enhances absorption by a further 35%. The complex angular momentum and T-matrix methods are used to show that the contribution to absorption by tunneling is diminished as the asphericity of spheroidal particles is increased. At an aspect ratio of 6 the contribution to the absorption that is due to tunneling is substantially reduced for oblate particles, whereas for prolate particles the tunneling contribution is reduced by 50% relative to the sphere.

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prediction on the weather, include extreme events, is now an advanced science whereby observations from a global network are assimilated into complex mathematical models. Forecasters also use the observations to fine-tune the model products and then issue warnings, Satellite based - remote sensing methods, add greatly to our observations database. The most obvious example, and one which saves many hundreds of lives, is the ability to detect and track tropical storms as they develop over the oceans before meeting land. Current remote sensing capabilities are reviewed with examples illustrating their application to different meteorological problems. (AU)

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