343 research outputs found

    Lifetime measurement of the metastable 3d 2D5/2 state in the 40Ca+ ion using the shelving technique on a few-ion string

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    We present a measurement of the lifetime of the metastable 3d 2D5/2 state in the 40Ca+ ion, using the so-called shelving technique on a string of five Doppler laser-cooled ions in a linear Paul trap. A detailed account of the data analysis is given, and systematic effects due to unwanted excitation processes and collisions with background gas atoms are discussed and estimated. From a total of 6805 shelving events, we obtain a lifetime tau=1149+/-14(stat.)+/-4(sys.)ms, a result which is in agreement with the most recent measurements.Comment: 10 pages, 7 figures. Submitted for publicatio

    The discovery of potent, selective, and reversible inhibitors of the house dust mite peptidase allergen Der p 1: an innovative approach to the treatment of allergic asthma.

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    Blocking the bioactivity of allergens is conceptually attractive as a small-molecule therapy for allergic diseases but has not been attempted previously. Group 1 allergens of house dust mites (HDM) are meaningful targets in this quest because they are globally prevalent and clinically important triggers of allergic asthma. Group 1 HDM allergens are cysteine peptidases whose proteolytic activity triggers essential steps in the allergy cascade. Using the HDM allergen Der p 1 as an archetype for structure-based drug discovery, we have identified a series of novel, reversible inhibitors. Potency and selectivity were manipulated by optimizing drug interactions with enzyme binding pockets, while variation of terminal groups conferred the physicochemical and pharmacokinetic attributes required for inhaled delivery. Studies in animals challenged with the gamut of HDM allergens showed an attenuation of allergic responses by targeting just a single component, namely, Der p 1. Our findings suggest that these inhibitors may be used as novel therapies for allergic asthma

    Predictors of Endotoxin Levels in U.S. Housing

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    A genome-wide association meta-analysis of self-reported allergy identifies shared and allergy-specific susceptibility loci

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    Allergic disease is very common and carries substantial public-health burdens. We conducted a meta-analysis of genome-wide associations with self-reported cat, dust-mite and pollen allergies in 53,862 individuals. We used generalized estimating equations to model shared and allergy-specific genetic effects. We identified 16 shared susceptibility loci with association P < 5 × 10-8, including 8 loci previously associated with asthma, as well as 4p14 near TLR1, TLR6 and TLR10 (rs2101521, P = 5.3 × 10 -21); 6p21.33 near HLA-C and MICA (rs9266772, P = 3.2 × 10 -12); 5p13.1 near PTGER4 (rs7720838, P = 8.2 × 10 -11); 2q33.1 in PLCL1 (rs10497813, P = 6.1 × 10-10), 3q28 in LPP (rs9860547, P = 1.2 × 10-9); 20q13.2 in NFATC2 (rs6021270, P = 6.9 × 10-9), 4q27 in ADAD1 (rs17388568, P = 3.9 × 10-8); and 14q21.1 near FOXA1 and TTC6 (rs1998359, P = 4.8 × 10-8). We identified one locus with substantial evidence of differences in effects across allergies at 6p21.32 in the class II human leukocyte antigen (HLA) region (rs17533090, P = 1.7 × 10-12), which was strongly associated with cat allergy. Our study sheds new light on the shared etiology of immune and autoimmune disease

    Dust Weight and Asthma Prevalence in the National Survey of Lead and Allergens in Housing (NSLAH)

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    BACKGROUND: Settled dust has been used in studies to assess exposures to allergens and other biologically active components, but it has not been considered in the aggregate in relation to respiratory health outcomes in the general population. OBJECTIVE: We addressed whether total house dust weight, an index of total dust exposure, was associated with respiratory health outcomes in the National Survey of Lead and Allergens in Housing (1998–1999) (NSLAH). METHODS: NSLAH was a cross-sectional survey designed to represent permanently occupied housing units in the United States. In each household, a questionnaire was administered and settled dust was vacuumed from five locations. Linear regression models were used to identify predictors of dust weight; logistic regression models were used to examine the relationship between dust weight and asthma and wheeze. RESULTS: Dust weight samples were available for 829 households, and survey information was available for 2,456 participants (children and adults). Lower income, older homes, household pets, having a smoker in the house, and less frequent cleaning predicted higher dust weight levels in U.S. households. Higher levels of dust weight were associated with greater odds of current asthma and wheeze. The strongest associations were seen for wheeze [adjusted odds ratio (OR) = 1.99; 95% confidence interval (CI), 1.21–3.28 for bedroom bed dust; OR = 2.81; 95% CI, 1.52–5.21 for upholstery dust). These associations persisted when adjusting for allergen and endotoxin exposures. CONCLUSIONS: Dust weight, an index of total dust exposure in the home, may contribute to respiratory outcomes independently of the exposure to specific components
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