Traffic evacuation time under nonhomogeneous conditions.

During many manmade and natural crises such as terrorist threats, floods, hazardous chemical and gas leaks, emergency personnel need to estimate the time in which people can evacuate from the affected urban area. Knowing an estimated evacuation time for a given crisis, emergency personnel can plan and prepare accordingly with the understanding that the actual evacuation time will take longer. Given the urban area to be evacuated, street widths exiting the area's perimeter, the area's population density, average vehicle occupancy, transport mode share and crawl speed, an estimation of traffic evacuation time can be derived. Peak-hour traffic data collected at three, midblock, Mumbai sites of varying geometric features and traffic composition were used in calibrating a model that estimates peak-hour traffic flow rates. Model validation revealed a correlation coefficient of +0.98 between observed and predicted peak-hour flow rates. A methodology is developed that estimates traffic evacuation time using the model.

Pharmacological modulation of cGMP levels by phosphodiesterase 5 inhibitors as a therapeutic strategy for treatment of respiratory pathology in cystic fibrosis.

The CFTR gene encodes a chloride channel with pleiotropic effects on cell physiology and metabolism. Here, we show that increasing cGMP levels to inhibit epithelial Na(+) channel in cystic fibrosis (CF) respiratory epithelial cells corrects several aspects of the downstream pathology in CF. Cell culture models, using a range of CF cell lines and primary cells, showed that complementary pharmacological approaches to increasing intracellular cGMP, by elevating guanyl cyclase activity though reduced nitric oxide, addition of cell-permeable cGMP analogs, or inhibition of phosphodiesterase 5 corrected multiple aspects of the CF pathological cascade. These included correction of defective protein glycosylation, bacterial adherence, and proinflammatory responses. Furthermore, pharmacological inhibition of phosphodiesterase 5 in tissues ex vivo or in animal models improved transepithelial currents across nasal mucosae from transgenic F508del Cftr(tm1Eur) mice and reduced neutrophil infiltration on bacterial aerosol challenge in Pseudomonas aeruginosa-susceptible DBA/2 mice. Our findings define phosphodiesterase 5 as a specific target for correcting a number of previously disconnected defects in the CF respiratory tract, now linked through this study. Our study suggests that phosphodiesterase 5 inhibition provides an opportunity for simultaneous and concerted correction of seemingly disparate complications in CF.

Endosomal hyperacidification in cystic fibrosis is due to defective nitric oxide-cylic GMP signalling cascade.

Endosomal hyperacidification in cystic fibrosis (CF) respiratory epithelial cells is secondary to a loss of sodium transport control owing to a defective form of the CF transmembrane conductance regulator CFTR. Here, we show that endosomal hyperacidification can be corrected by activating the signalling cascade controlling sodium channels through cyclic GMP. Nitric oxide (NO) donors corrected the endosomal hyperacidification in CF cells. Stimulation of CF cells with guanylate cyclase agonists corrected the pH in endosomes. Exposure of CF cells to an inhibitor of cGMP-specific phosphodiesterase PDE5, Sildenafil, normalized the endosomal pH. Treatment with Sildenafil reduced secretion by CF cells of the proinflammatory chemokine interleukin 8 following stimulation with Pseudomonas aeruginosa products. Thus, the endosomal hyperacidification and excessive proinflammatory response in CF are in part due to deficiencies in NO- and cGMP-regulated processes and can be pharmacologically reversed using PDE5 inhibitors.

Influential factors in freeway crash response and clearance times by emergency management services in peak periods.

OBJECTIVE: Various factors influence the time performance of emergency management personnel when a freeway traffic crash occurs. The proper identification and prioritization of factors that contribute to emergency management services' response times and clearance times result in better usage of taxpayer resources. METHOD: Use of a proportional hazard-based Cox-regression model analyzed statewide, peak-period, traffic crash data from 1999 Ohio logs. These data included time performance measures of emergency management services. RESULTS: Traffic crash severity had the most effect on response times. Those crashes involving injuries or fatalities had up to 20% less emergency management service response times than "property damage only" crashes. Environmental factors such as weather or roadway conditions had minimal effect on response times to traffic crashes. Day of week, urban or rural area, off or opposing-lane crash location, number of vehicles involved, heavy vehicle involvement, and response time significantly affected clearance time and the resulting total time during peak periods. CONCLUSIONS: By assessing resources currently dedicated to insignificant factors, emergency management services can further improve response times to those casualties that crucially need emergency services. By accurately identifying and deciphering traffic crash severity from initial field reports, services can further improve. Moreover, improvements in crash severity prediction reduce "false alarms" for emergency services. The improvements reduce the probability of a very short response time for a property damage only crash in which initial reports implied a very severe injury. By focusing on factors that significantly reduce traffic crash clearance times on freeways in peak periods, more reductions in average delay experienced by freeway users, in fuel consumption, and in motor vehicle emissions can occur.

Endosomal membrane traffic: convergence point targeted by Mycobacterium tuberculosis and HIV.

Inhibition of phagolysosome biogenesis in infected macrophages is a classical pathogenesis determinant of Mycobacterium tuberculosis. In this review we primarily cover the cellular mechanisms of M. tuberculosis phagosome maturation arrest. A detailed picture is beginning to emerge, involving regulators of membrane trafficking in mammalian cells and phagosomal interactions with endosomal organelles and the trans-Golgi network. We also present a hypothesis that overlaps may exist between the mycobacterial interference with the host cell membrane trafficking processes and the targeting of the late endosomal sorting machinery by HIV during viral budding in macrophages. We propose that interference with the endosomal sorting machinery contributes to the synergism between the two significant human diseases--AIDS and tuberculosis.