Traffic accidents at urban intersections result in a huge cost to society in tenns of death, injury, lost productivity, and property damage. Unfortunately, the elements that effect the frequency of intersection accidents are not well understood and, as a result, it is difficult to predict the effectiveness of specific intersection improvements that are aimed at reducing accident frequency. Using seven-yr accident histories from 63 intersections in Bellevue, Washington (all of which were targeted for operational improvements), this paper estimates a negative binomial regression of the frequency of accidents at intersection approaches. The estimation results uncover important interactions between geometric and traffic-related elements and accident frequencies. The findings of this paper provide exploratory methodological and empirical evidence that could lead to an approach to estimate the accident reduction benefits of various proposed improvements on operationally deficient intersections.

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The flavin-containing monooxygenases (FMOs) are important for xenobiotic metabolism. FMO3, the predominant FMO enzyme in human adult liver, exhibits significant interindividual variation that is poorly understood. This study was designed to identify common FMO3 genetic variants and determine their potential for contributing to interindividual differences in FMO3 expression. FMO3 single nucleotide polymorphism (SNP) discovery was accomplished by resequencing DNA samples from the Coriell Polymorphism Discovery Resource. Population-specific SNP frequencies were determined by multiplexed, singlebase extension using DNA from 201 Hispanic American (Mexican descent), 201 African American, and 200 White (northern European descent) subjects. Haplotypes were inferred and population frequencies estimated using PHASE version 2.1. Multiple site-directed mutagenesis was used to introduce inferred upstream haplotypes into an FMO3/luciferase construct for functional analysis in HepG2 cells. Sequence analysis revealed seven FMO3 upstream SNPs, 11 exon SNPs, and 22 intron SNPs. Five of the latter fell within consensus splice sites. A g.72GϾT variant (E24D) is predicted to impact the structure of the Rossmann fold involved in FAD binding, whereas a g.11177CϾA variant (N61K) is predicted to disrupt the secondary structure of a conserved membrane interaction domain. Seven common (Ͼ1%) promoter region haplotypes were inferred in one or more of the study populations that differed in estimated frequency among the groups. Haplotype 2 resulted in an 8-fold increase in promoter activity, whereas haplotypes 8 and 15 exhibited a near complete loss of activity. In conclusion, FMO3 promoter haplotype variants modulate gene function and probably contribute to interindividual differences in FMO3 expression.The flavin-containing monooxygenases (FMOs) (EC 1.14.13.8) are a family of NADPH-and oxygen-dependent microsomal enzymes involved in the oxidative metabolism of many nucleophilic nitrogen-, sulfur-and phosphorouscontaining drugs and toxicants (Cashman, 2002). Multiple human FMO genes have been identified: a five-gene cluster at 1q24.3 (FMO1-4 and FMO6p) that encodes four active enzymes (FMO1-4), a second cluster of five genes at 1q24.2 (FMO7p-11p), all representing pseudogenes, and a single gene, FMO5, at 1q21

Flavin-containing monooxygenases (FMOs) are important for the disposition of many therapeutics, environmental toxicants, and nutrients. FMO3, the major adult hepatic FMO enzyme, exhibits significant interindividual variation. Eighteen FMO3 single-nucleotide polymorphism (SNP) frequencies were determined in 202 Hispanics (Mexican descent), 201 African Americans, and 200 non-Latino whites. Using expressed recombinant enzyme with methimazole, trimethylamine, sulindac, and ethylenethiourea, the novel structural variants FMO3 E24D and K416N were shown to cause modest changes in catalytic efficiency, whereas a third novel variant, FMO3 N61K, was essentially devoid of activity. The latter variant was present at an allelic frequency of 5.2% in non-Latino whites and 3.5% in African Americans, but it was absent in Hispanics. Inferring haplotypes using PHASE, version 2.1, the greatest haplotype diversity was observed in African Americans followed by nonLatino whites and Hispanics. Haplotype 2A and 2B, consisting of a hypermorphic promoter SNP cluster (-2650CϾG, -2543TϾA, and -2177GϾC) in linkage with synonymous structural variants was inferred at a frequency of 27% in the Hispanic population, but only 5% in non-Latino whites and African Americans. This same promoter SNP cluster in linkage with one or more hypomorphic structural variant also was inferred in multiple haplotypes at a total frequency of 5.6% in the AfricanAmerican study group but less than 1% in the other two groups. The sum frequencies of the hypomorphic haplotypes H3 [15,167GϾA (E158K)], H5B [-2650CϾG, 15,167GϾA (E158K), 21,375CϾT (N285N), 21,443AϾG (E308G)], and H6 [15,167GϾA (E158K), 21,375CϾT (N285N)] was 28% in Hispanics, 23% in non-Latino whites, and 24% in African Americans.The flavin-containing monooxygenases (FMOs; EC 1.14.13.8) are a family of microsomal enzymes that catalyze the NADPH-dependent N-and S-oxidation of a variety of therapeutics, environmental toxicants, carcinogens, and nutrients (Krueger and Williams, 2005). The FMO multigene family consists of a five-gene cluster at 1q24.3 (FMO1-4 and FMO6p), a second cluster of five genes at 1q24.2 (FMO7p-11p), and a single gene, FMO5, at 1q21.1, encoding a total of five active proteins in the human (Hernandez et al., 2004).The most recent common precursor for all placental mammals is predicted to have already had a cluster containing FMO1-6P and a separate FMO5 locus that arose from duplication of an ancestral gene approximately 210 to 275 million years ago (Hernandez et al., 2004). Despite the antiquity of the FMO gene family, a sequence comparison among modern FMO enzymes reveals 76 to 86% sequence identity between orthologous proteins, suggesting these genes have been highly conserved.The individual FMO enzymes exhibit broad but distinct substrate specificities (Krueger and Williams, 2005) as well as species-, sex-, tissue-, and age-dependent differences in expression patterns (for review, see Hines, 2006). In the human, FMO3 is the predominant adult hepatic enzyme with a specific conten...

Various biological materials were tested for their growth-promoting activity of several bifidobacterial species in a synthetic medium containing ample sources of inorganic salts, vitamins, nitrogen, and carbon. It was found that only Bifidobacterium adolescentis and B. longum (ATCC 15708) grew optimally or near optimally in the synthetic medium. All the other bifidobacteria tested grew optimally only in the synthetic medium supplemented with a growth promoter. The best growth promoters for all bacteria were bovine casein digest and yeast extract rather than human milk whey. Other growth promoters, including human and bovine milk wheys, hog gastric mucin, and bovine serum albumin digest were effective with some bacterial species but not with others. Bifidobacteria also grew well when the bovine casein digest (20 mg/ml) was used as the nitrogen source. Only the yeast extract was able to improve growth under these circumstances. The nature of these growth factors has not yet been determined.