Aspergillus fumigatus is the most common cause of invasive mold disease in humans. The mechanisms underlying the adherence of this mold to host cells and macromolecules have remained elusive. Using mutants with different adhesive properties and comparative transcriptomics, we discovered that the gene uge3, encoding a fungal epimerase, is required for adherence through mediating the synthesis of galactosaminogalactan. Galactosaminogalactan functions as the dominant adhesin of A. fumigatus and mediates adherence to plastic, fibronectin, and epithelial cells. In addition, galactosaminogalactan suppresses host inflammatory responses in vitro and in vivo, in part through masking cell wall β-glucans from recognition by dectin-1. Finally, galactosaminogalactan is essential for full virulence in two murine models of invasive aspergillosis. Collectively these data establish a role for galactosaminogalactan as a pivotal bifunctional virulence factor in the pathogenesis of invasive aspergillosis.
BACKGROUND Distracted driving attributable to the performance of secondary tasks is a major cause of motor vehicle crashes both among teenagers who are novice drivers and among adults who are experienced drivers. METHODS We conducted two studies on the relationship between the performance of secondary tasks, including cell-phone use, and the risk of crashes and near-crashes. To facilitate objective assessment, accelerometers, cameras, global positioning systems, and other sensors were installed in the vehicles of 42 newly licensed drivers (16.3 to 17.0 years of age) and 109 adults with more driving experience. RESULTS During the study periods, 167 crashes and near-crashes among novice drivers and 518 crashes and near-crashes among experienced drivers were identified. The risk of a crash or near-crash among novice drivers increased significantly if they were dialing a cell phone (odds ratio, 8.32; 95% confidence interval [CI], 2.83 to 24.42), reaching for a cell phone (odds ratio, 7.05; 95% CI, 2.64 to 18.83), sending or receiving text messages (odds ratio, 3.87; 95% CI, 1.62 to 9.25), reaching for an object other than a cell phone (odds ratio, 8.00; 95% CI, 3.67 to 17.50), looking at a roadside object (odds ratio, 3.90; 95% CI, 1.72 to 8.81), or eating (odds ratio, 2.99; 95% CI, 1.30 to 6.91). Among experienced drivers, dialing a cell phone was associated with a significantly increased risk of a crash or near-crash (odds ratio, 2.49; 95% CI, 1.38 to 4.54); the risk associated with texting or accessing the Internet was not assessed in this population. The prevalence of high-risk attention to secondary tasks increased over time among novice drivers but not among experienced drivers. CONCLUSIONS The risk of a crash or near-crash among novice drivers increased with the performance of many secondary tasks, including texting and dialing cell phones. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Highway Traffic Safety Administration.)
In this paper, we show a direct relation between spectral embedding methods and kernel PCA, and how both are special cases of a more general learning problem, that of learning the principal eigenfunctions of an operator defined from a kernel and the unknown data generating density.
Purpose-The high crash rates of novice teenage drivers are thought to be due to inexperience and risky driving behavior, exacerbated by passengers, night, and other complex driving conditions. This research examined factors associated with crash/near crash and risky driving rates among novice teenagers, including night vs day, passenger presence and characteristics, and driver psychosocial factors.Method-The vehicles of 42 newly-licensed teenage drivers were equipped with recording systems that collected data on driving performance and occupant characteristics during their first 18 months of licensure. Survey data were collected at four measurement times. Poisson regression with random effects was used to analyze crash/near crash and elevated g-force event rates (i.e., risky driving); incident rate ratios (IRRs) measured associations with covariates.Results-Crash/near crash rates among novice teenagers were 75% lower in the presence of adult passengers and 96% higher among those with risky friends. Teenage risky driving was 67% lower with adult passengers, 18% lower with teenage passengers; 20% lower during early night than day; and 109% higher among teens with relatively more risky friends.Conclusions-The low rate of risky driving in the presence of adult passengers suggests that teens can drive in less risky fashion. The higher rate of risky driving among those with risky friends suggests that risky driving may be socially influenced.
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