Association of FEV1 in asthmatic children with personal and microenvironmental exposure to airborne particulate matter.

Exposure to particulate matter (PM) air pollution has been shown to exacerbate children's asthma, but the exposure sources and temporal characteristics are still under study. Children's exposure to PM is likely to involve both combustion-related ambient PM and PM related to a child's activity in various indoor and outdoor microenvironments. Among 19 children with asthma, 9-17 years of age, we examined the relationship of temporal changes in percent predicted forced expiratory volume in 1 sec (FEV1) to personal continuous PM exposure and to 24-hr average gravimetric PM mass measured at home and central sites. Subjects were followed for 2 weeks during either the fall of 1999 or the spring of 2000, in a southern California region affected by transported air pollution. FEV(subscript)1(/subscript) was measured by subjects in the morning, afternoon, and evening. Exposure measurements included continuous PM using a passive nephelometer carried by subjects; indoor, outdoor home, and central-site 24-hr gravimetric PM2.5 (PM of aerodynamic diameter < 2.5 microm) and PM10; and central-site hourly PM10, nitrogen dioxide, and ozone. Data were analyzed with linear mixed models controlling for within-subject autocorrelation, FEV1 maneuver time, and exposure period. We found inverse associations of FEV1 with increasing PM exposure during the 24 hr before the FEV1 maneuver and with increasing multiday PM averages. Deficits in percent predicted FEV1 (95% confidence interval) for given PM interquartile ranges measured during the preceding 24-hr were as follows: 128 microg/m3 1-hr maximum personal PM, -6.0% (-10.5 to -1.4); 30 microg/m3 24-hr average personal PM, -5.9% (-10.8 to -1.0); 6.7 microg/m3 indoor home PM2.5, -1.6% (-2.8 to -0.4); 16 microg/m3 indoor home PM10, -2.1% (-3.7 to -0.4); 7.1 microg/m3 outdoor home PM2.5, -1.1% (-2.4 to 0.1); and 7.5 microg/m3 central-site PM2.5, -0.7% (-1.9 to 0.4). Stronger associations were found for multiday moving averages of PM for both personal and stationary-site PM. Stronger associations with personal PM were found in boys allergic to indoor allergens. FEV1 was weakly associated with NO2 but not with O3. Results suggest mixed respiratory effects of PM in asthmatic children from both ambient background exposures and personal exposures in various microenvironments

A Method for Assaying Deubiquitinating Enzymes

A general method for the assay of deubiquitinating enzymes was described in detail using (125)I-labeled ubiquitin-fused αNH-MHISPPEPESEEEEEHYC (referred to as Ub-PESTc) as a substrate. Since the tyrosine residue in the PESTc portion of the fusion protein was almost exclusively radioiodinated under a mild labeling condition, such as using IODO-BEADS, the enzymes could be assayed directly by simple measurement of the radioactivity released into acid soluble products. Using this assay protocol, we could purify six deubiquitinating enzymes from chick skeletal muscle and yeast and compare their specific activities. Since the extracts of E. coli showed little or no activity against the substrate, the assay protocol should be useful for identification and purification of eukaryotic deubiquitinating enzymes cloned and expressed in the cells

In Vivo Delivery of Gremlin siRNA Plasmid Reveals Therapeutic Potential against Diabetic Nephropathy by Recovering Bone Morphogenetic Protein-7

Diabetic nephropathy is a complex and poorly understood disease process, and our current treatment options are limited. It remains critical, then, to identify novel therapeutic targets. Recently, a developmental protein and one of the bone morphogenetic protein antagonists, Gremlin, has emerged as a novel modulator of diabetic nephropathy. The high expression and strong co-localization with transforming growth factor- β1 in diabetic kidneys suggests a role for Gremlin in the pathogenesis of diabetic nephropathy. We have constructed a gremlin siRNA plasmid and have examined the effect of Gremlin inhibition on the progression of diabetic nephropathy in a mouse model. CD-1 mice underwent uninephrectomy and STZ treatment prior to receiving weekly injections of the plasmid. Inhibition of Gremlin alleviated proteinuria and renal collagen IV accumulation 12 weeks after the STZ injection and inhibited renal cell proliferation and apoptosis. In vitro experiments, using mouse mesangial cells, revealed that the transfect ion of gremlin siRNA plasmid reversed high glucose induced abnormalities, such as increased cell proliferation and apoptosis and increased collagen IV production. The decreased matrix metalloprotease level was partially normalized by transfection with gremlin siRNA plasmid. Additionally, we observed recovery of bone morphogenetic protein-7 signaling activity, evidenced by increases in phosphorylated Smad 5 protein levels. We conclude that inhibition of Gremlin exerts beneficial effects on the diabetic kidney mainly through maintenance of BMP-7 activity and that Gremlin may serve as a novel therapeutic target in the management of diabetic nephropathy

Particle motion and heat transfer in an upward-flowing dense particle suspension: application in solar receivers

Concentrated solar power (CSP) plants conventionally make use of molten salt as the heat transfer medium, which transfers heat between the solar receiver and a steam turbine power circuit. A new approach uses particles of a heat-resistant particulate medium in the form of many dense upward-moving fluidised beds contained within an array of vertical tubes within the solar receiver. In most dense gas-solid fluidisation systems, particle circulation is induced by bubble motion and is the primary cause of particle convective heat transfer, which is the major contributing mechanism to overall heat transfer. The current work describes experiments designed to investigate the relationship between this solids convection and the heat transfer coefficient between the bed and the tube wall, which is shown to depend on the local particle concentration and their rate of renewal at the wall. Experiments were performed using 65 µm silicon carbide particles in a tube of diameter 30mm, replicating the conditions used in the real application. Solids motion and time-averaged solids concentration were measured using Positron Emission Particle Tracking (PEPT) and local heat transfer coefficients measured using small probes which employ electrical resistance heating and thermocouple temperature measurement. Results show that, as for other types of bubbling beds, the heat transfer coefficient first increases as the gas flow rate increases (because the rate of particle renewal at the wall increases), before passing through a maximum and decreasing again as the reducing local solids concentration at the wall becomes the dominant effect. Measured heat transfer coefficients are compared with theoretical approaches by Mickley and Fairbanks packet model and Thring correlation. The close correspondence between heat transfer coefficient and solids movement is here demonstrated by PEPT for the first time in a dense upward-moving fluidised bed