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- Gudbjartsson, Daniel F., et al.
(författare)
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Sequence variants affecting eosinophil numbers associate with asthma and myocardial infarction
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 41:3, s. 342-347
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Tidskriftsartikel (refereegranskat)abstract
- Eosinophils are pleiotropic multifunctional leukocytes involved in initiation and propagation of inflammatory responses and thus have important roles in the pathogenesis of inflammatory diseases. Here we describe a genome-wide association scan for sequence variants affecting eosinophil counts in blood of 9,392 Icelanders. The most significant SNPs were studied further in 12,118 Europeans and 5,212 East Asians. SNPs at 2q12 (rs1420101), 2q13 (rs12619285), 3q21 (rs4857855), 5q31 (rs4143832) and 12q24 (rs3184504) reached genome-wide significance (P = 5.3 x 10(-14), 5.4 x 10(-10), 8.6 x 10(-17), 1.2 x 10(-10) and 6.5 x 10(-19), respectively). A SNP at IL1RL1 associated with asthma (P = 5.5 x 10(-12)) in a collection of ten different populations (7,996 cases and 44,890 controls). SNPs at WDR36, IL33 and MYB that showed suggestive association with eosinophil counts were also associated with atopic asthma (P = 4.2 x 10(-6), 2.2 x 10(-5) and 2.4 x 10(-4), respectively). We also found that a nonsynonymous SNP at 12q24, in SH2B3, associated significantly (P = 8.6 x 10(-8)) with myocardial infarction in six different populations (6,650 cases and 40,621 controls).
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| 2. |
- Watson, L, et al.
(författare)
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Predictors of lung function and its decline in mild to moderate COPD in association with gender: Results from the Euroscop study
- 2006
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Ingår i: Respiratory Medicine. - : Elsevier BV. - 1532-3064 .- 0954-6111. ; 100:4, s. 746-753
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is increasing appreciation of gender differences in COPD but scant data whether risk factors for tow lung function differ in men and women. We analysed data from 3 years follow-up in 178 women and 464 men with COPD, participants in the Euroscop Study who were smokers unexposed to inhaled corticosteroids. Methods: Explanatory variables of gender, age, starting age and pack-years smoking, respiratory symptoms, FEV1%FVC and FEV1%IVC (clinically important measures of airway obstruction), body mass index (BMI), and change in smoking were included in multiple linear regression models with baseline and change in postbronchodilator FEV1 as dependent variables. Results: Reduced baseline FEV1 was associated with respiratory symptoms in men only. Annual decline in FEV1 was not associated with respiratory symptoms in either men or women, and was 55 ml less in obese men (BMI >= 30 kg/m(2)) than men having normal BMI, an effect not seen in women. It was 32ml faster in women with FEV1%FVC < median than women with less airway obstruction, a larger difference than in men (8ml per year). It was 17.7ml/year faster when increasing the daily number of cigarettes by 10 in men only, but not significantly greater than in women. Conclusion: Respiratory symptoms were associated with reduced baseline FEV, in men with COPD. In men, obesity was associated with reduced decline and increasing the number of cigarettes smoked with increased decline in lung function. In women more severe airway obstruction was associated with accelerated decline.
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| 3. |
- Bosch, Petra, 1971, et al.
(författare)
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Cooperative innovation projects: Capabilities and Governance Mechanisms
- 2009
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Ingår i: Journal of Product Innovation Management. - : Wiley. - 0737-6782 .- 1540-5885. ; 26:1, s. 58-70
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Tidskriftsartikel (refereegranskat)abstract
- This paper is concerned with how firms in a project-based industry cooperate in technological innovation projects in the construction industry. The main focus of the paper is on the sharing of capabilities in cooperative innovation projects and how these cooperations are governed. A knowledge-based perspective is applied, and four cooperative innovation projects in the construction industry are compared. Based on the case studies, a set of propositions is defined. First, a cooperation aimed at a mutual strategic benefit in mutually gaining access to the knowledge bases of the involved firms, while maintaining their own differentiated knowledge base, can result in more stable and long term relationships with mutual trust between the cooperating firms. Second, in a cooperation aimed at a mutual strategic benefit in mutually gaining access to the knowledge bases of the involved firms, partners not only gain access to each other's technological capabilities but also develop and share knowledge about organizational aspects and market situations and gain knowledge about the way of working of the partner firm. Third, in a cooperation aimed at mutual strategic benefit in mutually gaining access to the knowledge bases of the involved firms, noncodifiability of the capabilities is conditional to create a win–win situation. And fourth, cooperation aimed at a mutual strategic benefit in mutually gaining access to the knowledge bases of the involved firms is based on mutual competence and intentional trust as its main governance mechanism, whereas contracting between market parties aimed at knowledge–output transactions is represented by limited trust and arms' length (contractual) relationships as its main governance mechanism.
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| 4. |
- Pantazis, Antonios, 1982-, et al.
(författare)
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The Effect of Neuronal Morphology and Membrane-permeant Weak Acid and Base on the Dissipation of Depolarization-induced pH Gradients in Snail Neurons
- 2006
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Ingår i: Pflügers Archiv. - : Springer. - 0031-6768 .- 1432-2013. ; 452:2, s. 175-187
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Tidskriftsartikel (refereegranskat)abstract
- Neuronal depolarization causes larger intracellular pH (pHi) shifts in axonal and dendritic regions than in the cell body. In this paper, we present evidence relating the time for collapse of these gradients to neuronal morphology. We have used ratiometric pHi measurements using 8-hydroxypyrene-1,3,6-trisulfonic acid (HPTS) in whole-cell patch-clamped snail neurons to study the collapse of longitudinal pH gradients. Using depolarization to open voltage-gated proton channels, we produced alkaline pHi microdomains. In the absence of added mobile buffers, facilitated H+ diffusion down the length of the axon plays a critical role in determining pHi microdomain lifetime, with axons of ∼100 μm allowing pH differences to be maintained for >60 s. An application of mobile, membrane-permeant pH buffers accelerated the collapse of the alkaline-pH gradients but, even at 30 mM, was unable to abolish them. Modeling of the pHi dynamics showed that both the relatively weak effect of the weak acid/base on the peak size of the pH gradient and the accelerated collapse of the pH gradient could be due to the time taken for equilibration of the weak acid and base across the cell. We propose that appropriate weak acid/base mixes may provide a simple method for studying the role of local pHi signals without perturbing steady-state pHi. Furthermore, an extrapolation of our in vitro data to longer and thinner neuronal structures found in the mammalian nervous system suggests that dendritic and axonal pHi are likely to be dominated by local pHi-regulating mechanisms rather than simply following the soma pHi.
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