| 1. |
- Aad, G., et al.
(author)
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Readiness of the ATLAS Tile Calorimeter for LHC collisions
- 2010
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In: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 70:4, s. 1193-1236
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Journal article (peer-reviewed)abstract
- The Tile hadronic calorimeter of the ATLAS detector has undergone extensive testing in the experimental hall since its installation in late 2005. The readout, control and calibration systems have been fully operational since 2007 and the detector has successfully collected data from the LHC single beams in 2008 and first collisions in 2009. This paper gives an overview of the Tile Calorimeter performance as measured using random triggers, calibration data, data from cosmic ray muons and single beam data. The detector operation status, noise characteristics and performance of the calibration systems are presented, as well as the validation of the timing and energy calibration carried out with minimum ionising cosmic ray muons data. The calibration systems' precision is well below the design value of 1%. The determination of the global energy scale was performed with an uncertainty of 4%.
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| 2. |
- O'Connor, C. M., et al.
(author)
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Effect of nesiritide in patients with acute decompensated heart failure
- 2011
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In: The New England journal of medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 365:1, s. 32-43
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Journal article (peer-reviewed)abstract
- BACKGROUND: Nesiritide is approved in the United States for early relief of dyspnea in patients with acute heart failure. Previous meta-analyses have raised questions regarding renal toxicity and the mortality associated with this agent. METHODS: We randomly assigned 7141 patients who were hospitalized with acute heart failure to receive either nesiritide or placebo for 24 to 168 hours in addition to standard care. Coprimary end points were the change in dyspnea at 6 and 24 hours, as measured on a 7-point Likert scale, and the composite end point of rehospitalization for heart failure or death within 30 days. RESULTS: Patients randomly assigned to nesiritide, as compared with those assigned to placebo, more frequently reported markedly or moderately improved dyspnea at 6 hours (44.5% vs. 42.1%, P=0.03) and 24 hours (68.2% vs. 66.1%, P=0.007), but the prespecified level for significance (P
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| 3. |
- den Hollander, J, et al.
(author)
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Aurora kinases A and B are up-regulated by Myc and are essential for maintenance of the malignant state
- 2010
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In: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 116:9, s. 1498-1505
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Journal article (peer-reviewed)abstract
- Myc oncoproteins promote continuous cell growth, in part by controlling the transcription of key cell cycle regulators. Here, we report that c-Myc regulates the expression of Aurora A and B kinases (Aurka and Aurkb), and that Aurka and Aurkb transcripts and protein levels are highly elevated in Myc-driven B-cell lymphomas in both mice and humans. The induction of Aurka by Myc is transcriptional and is directly mediated via E-boxes, whereas Aurkb is regulated indirectly. Blocking Aurka/b kinase activity with a selective Aurora kinase inhibitor triggers transient mitotic arrest, polyploidization, and apoptosis of Myc-induced lymphomas. These phenotypes are selectively bypassed by a kinase inhibitor-resistant-Aurkb mutant, demonstrating that Aurkb is the primary therapeutic target in the context of Myc. Importantly, apoptosis provoked by Aurk inhibition was p53 independent, suggesting that Aurka/Aurkb inhibitors will show efficacy in treating primary or relapsed malignancies having Myc involvement and/or loss of p53 function. (Blood. 2010;116(9):1498-1505)
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| 4. |
- Hollander, A., et al.
(author)
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Assessing the Relative Importance of Spatial Variability in Emissions Versus Landscape Properties in Fate Models for Environmental Exposure Assessment of Chemicals
- 2012
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In: Environmental Modelling and Assessment. - : Springer Science and Business Media LLC. - 1420-2026 .- 1573-2967. ; 17:6, s. 577-587
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Journal article (peer-reviewed)abstract
- Multimedia mass balance models differ in their treatment of spatial resolution from single boxes representing an entire region to multiple interconnected boxes with varying landscape properties and emission intensities. Here, model experiments were conducted to determine the relative importance of these two main factors that cause spatial variation in environmental chemical concentrations: spatial patterns in emission intensities and spatial differences in environmental conditions. In the model, experiments emissions were always to the air compartment. It was concluded that variation in emissions is in most cases the dominant source of variation in environmental concentrations. It was found, however, that variability in environmental conditions can strongly influence predicted concentrations in some cases, if the receptor compartments of interest are soil or water-for water concentrations particularly if a chemical has a high octanol-air partition coefficient (K-oa). This information will help to determine the required level of spatial detail that suffices for a specific regulatory purpose.
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| 5. |
- Smailhodzic, Dzenita, et al.
(author)
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Zinc supplementation inhibits complement activation in age-related macular degeneration.
- 2014
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:11
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Journal article (peer-reviewed)abstract
- Age-related macular degeneration (AMD) is the leading cause of blindness in the Western world. AMD is a multifactorial disorder but complement-mediated inflammation at the level of the retina plays a pivotal role. Oral zinc supplementation can reduce the progression of AMD but the precise mechanism of this protective effect is as yet unclear. We investigated whether zinc supplementation directly affects the degree of complement activation in AMD and whether there is a relation between serum complement catabolism during zinc administration and the complement factor H (CFH) gene or the Age-Related Maculopathy susceptibility 2 (ARMS2) genotype. In this open-label clinical study, 72 randomly selected AMD patients in various stages of AMD received a daily supplement of 50 mg zinc sulphate and 1 mg cupric sulphate for three months. Serum complement catabolism-defined as the C3d/C3 ratio-was measured at baseline, throughout the three months of supplementation and after discontinuation of zinc administration. Additionally, downstream inhibition of complement catabolism was evaluated by measurement of anaphylatoxin C5a. Furthermore, we investigated the effect of zinc on complement activation in vitro. AMD patients with high levels of complement catabolism at baseline exhibited a steeper decline in serum complement activation (p<0.001) during the three month zinc supplementation period compared to patients with low complement levels. There was no significant association of change in complement catabolism and CFH and ARMS2 genotype. In vitro zinc sulphate directly inhibits complement catabolism in hemolytic assays and membrane attack complex (MAC) deposition on RPE cells. This study provides evidence that daily administration of 50 mg zinc sulphate can inhibit complement catabolism in AMD patients with increased complement activation. This could explain part of the mechanism by which zinc slows AMD progression.
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| 6. |
- Butlin, Roger, 1955, et al.
(author)
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PARALLEL EVOLUTION OF LOCAL ADAPTATION AND REPRODUCTIVE ISOLATION IN THE FACE OF GENE FLOW
- 2014
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In: Evolution. - : Wiley. - 0014-3820. ; 68:4, s. 935-949
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Journal article (peer-reviewed)abstract
- Parallel evolution of similar phenotypes provides strong evidence for the operation of natural selection. Where these phenotypes contribute to reproductive isolation, they further support a role for divergent, habitat-associated selection in speciation. However, the observation of pairs of divergent ecotypes currently occupying contrasting habitats in distinct geographical regions is not sufficient to infer parallel origins. Here we show striking parallel phenotypic divergence between populations of the rocky-shore gastropod, Littorina saxatilis, occupying contrasting habitats exposed to either wave action or crab predation. This divergence is associated with barriers to gene exchange but, nevertheless, genetic variation is more strongly structured by geography than by ecotype. Using approximate Bayesian analysis of sequence data and amplified fragment length polymorphism markers, we show that the ecotypes are likely to have arisen in the face of continuous gene flow and that the demographic separation of ecotypes has occurred in parallel at both regional and local scales. Parameter estimates suggest a long delay between colonization of a locality and ecotype formation, perhaps because the postglacial spread of crab populations was slower than the spread of snails. Adaptive differentiation may not be fully genetically independent despite being demographically parallel. These results provide new insight into a major model of ecologically driven speciation.
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| 7. |
- de Hollander, Ellen L., et al.
(author)
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The association between waist circumference and risk of mortality considering body mass index in 65-to 74-year-olds : a meta-analysis of 29 cohorts involving more than 58 000 elderly persons
- 2012
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In: International Journal of Epidemiology. - : OXFORD UNIV PRESS. - 0300-5771 .- 1464-3685. ; 41:3, s. 805-817
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Journal article (peer-reviewed)abstract
- Background For the elderly, the association between waist circumference (WC) and mortality considering body mass index (BMI) remains unclear, and thereby also the evidence base for using these anthropometric measures in clinical practice. This meta-analysis examined the association between WC categories and (cause-specific) mortality within BMI categories. Furthermore, the association of continuous WC with lowest and increased mortality risks was examined. Methods Age-and smoking-adjusted relative risks (RRs) of mortality associated with WC-BMI categories and continuous WC (including WC and WC2) were calculated by the investigators and pooled by means of random-effects models. Results During a 5-year-follow-up of 32 678 men and 25 931 women, we ascertained 3318 and 1480 deaths, respectively. A large WC (men: >= 102 cm, women: >= 88 cm) was associated with increased all-cause mortality RRs for those in the 'healthy' weight {1.7 [95% confidence interval (CI): 1.2-2.2], 1.7 (95% CI: 1.3-2.3)}, overweight [1.1(95% CI: 1.0-1.3), 1.4 (95%: 1.1-1.7)] and obese [1.1 (95% CI: 1.0-1.3), 1.6 (95% CI: 1.3-1.9)] BMI category compared with the 'healthy' weight (20-24.9 kg/m(2)) and a small WC (<94 cm, men; <80 cm, women) category. Underweight was associated with highest all-cause mortality RRs in men [2.2 (95% CI: 1.8-2.8)] and women [2.3 (95% CI: 1.8-3.1]. We found a J-shaped association for continuous WC with all-cause, cardiovascular (CVD) and cancer, and a U-shaped association with respiratory disease mortality (P < 0.05). An all-cause (CVD) mortality RR of 2.0 was associated with a WC of 132 cm (123 cm) in men and 116 cm (105 cm) in women. Conclusions Our results showed increased mortality risks for elderly people with an increased WC-even across BMI categories- and for those who were classified as 'underweight' using BMI. The results provide a solid basis for re-evaluation of WC cut-points in ageing populations.
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| 8. |
- Littink, Karin W., et al.
(author)
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Homozygosity Mapping in Patients with Cone-Rod Dystrophy : Novel Mutations and Clinical Characterizations
- 2010
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In: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 51:11, s. 5943-5951
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Journal article (peer-reviewed)abstract
- PURPOSE. To determine the genetic defect and to describe the clinical characteristics in a cohort of mainly nonconsanguineous cone-rod dystrophy (CRD) patients. METHODS. One hundred thirty-nine patients with diagnosed CRD were recruited. Ninety of them were screened for known mutations in ABCA4, and those carrying one or two mutations were excluded from further research. Genome-wide homozygosity mapping was performed in the remaining 108. Known genes associated with autosomal recessive retinal dystrophies located within a homozygous region were screened for mutations. Patients in whom a mutation was detected underwent further ophthalmic examination. RESULTS. Homozygous sequence variants were identified in eight CRD families, six of which were nonconsanguineous. The variants were detected in the following six genes: ABCA4, CABP4, CERKL, EYS, KCNV2, and PROM1. Patients carrying mutations in ABCA4, CERKL, and PROM1 had typical CRD symptoms, but a variety of retinal appearances on funduscopy, optical coherence tomography, and autofluorescence imaging. CONCLUSIONS. Homozygosity mapping led to the identification of new mutations in consanguineous and nonconsanguineous patients with retinal dystrophy. Detailed clinical characterization revealed a variety of retinal appearances, ranging from nearly normal to extensive retinal remodeling, retinal thinning, and debris accumulation. Although CRD was initially diagnosed in all patients, the molecular findings led to a reappraisal of the diagnosis in patients carrying mutations in EYS, CABP4, and KCNV2.
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| 9. |
- Wientzek, Angelika, et al.
(author)
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Cross-Sectional Associations of Objectively Measured Physical Activity, Cardiorespiratory Fitness and Anthropometry in European Adults
- 2014
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In: Obesity. - : Wiley. - 1930-7381 .- 1930-739X. ; 22:5, s. E127-E134
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Journal article (peer-reviewed)abstract
- Objective: To quantify the independent associations between objectively measured physical activity (PA), cardiorespiratory fitness (CRF), and anthropometry in European men and women. Methods: 2,056 volunteers from 12 centers across Europe were fitted with a heart rate and movement sensor at 2 visits 4 months apart for a total of 8 days. CRF (ml/kg/min) was estimated from an 8 minute ramped step test. A cross-sectional analysis of the independent associations between objectively measured PA (m/s(2)/d), moderate and vigorous physical activity (MVPA) (% time/d), sedentary time (% time/d), CRF, and anthropometry using sex stratified multiple linear regression was performed. Results: In mutually adjusted models, CRF, PA, and MVPA were inversely associated with all anthropometric markers in women. In men, CRF, PA, and MVPA were inversely associated with BMI, whereas only CRF was significantly associated with the other anthropometric markers. Sedentary time was positively associated with all anthropometric markers, however, after adjustment for CRF significant in women only. Conclusion: CRF, PA, MVPA, and sedentary time are differently associated with anthropometric markers in men and women. CRF appears to attenuate associations between PA, MVPA, and sedentary time. These observations may have implications for prevention of obesity.
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| 10. |
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