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- Wild, W., et al.
(författare)
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Millimetron—a large Russian-European submillimeter space observatory
- 2009
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Ingår i: Experimental Astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 23:1, s. 221-244
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Tidskriftsartikel (refereegranskat)abstract
- Millimetron is a Russian-led 12 m diameter submillimeter and far-infrared space observatory which is included in the Space Plan of the Russian Federation for launch around 2017. With its large collecting area and state-of-the-art receivers, it will enable unique science and allow at least one order of magnitude improvement with respect to the Herschel Space Observatory. Millimetron will be operated in two basic observing modes: as a single-dish observatory, and as an element of a ground-space very long baseline interferometry (VLBI) system. As single-dish, angular resolutions on the order of 3 to 12 arc sec will be achieved and spectral resolutions of up to a million employing heterodyne techniques. As VLBI antenna, the chosen elliptical orbit will provide extremely large VLBI baselines (beyond 300,000 km) resulting in micro-arc second angular resolution.
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| 3. |
- Gao, W G, et al.
(författare)
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Risk prediction models for the development of diabetes in Mauritian Indians
- 2009
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Ingår i: Diabetic Medicine. - : Wiley. - 0742-3071 .- 1464-5491. ; 26:10, s. 996-1002
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: To develop risk prediction models of future diabetes in Mauritian Indians. METHODS: Three thousand and ninety-four Mauritian Indians (1141 men, aged 20-65 years) without diabetes in 1987 or 1992 were followed up to 1992 or 1998. Subjects underwent repeated oral glucose tolerance tests and diabetes was diagnosed according to 2006 World Health Organization/International Diabetes Federation criteria. Cox regression models for interval censored data were performed using data from 1544 randomly selected participants. Predicted probabilities for diabetes were calculated and validated in the remaining 1550 subjects. RESULTS: Over 11 years of follow-up, there were 511 cases of diabetes. Among variables tested, family history of diabetes, obesity (body mass index, waist circumference) and glucose were significant predictors of diabetes. Predicted probabilities derived from a simple model fitted with sex, family history of diabetes and obesity ranged from 0.05 to 0.64 in men and 0.03 to 0.49 in women. To predict the onset of diabetes, area under the receiver operating characteristic (ROC) curve (AROC) of predicted probabilities was 0.62 (95% confidence interval, 0.56-0.68) in men and 0.64 (0.59-0.69) in women. At a cut-off point of 0.12, the sensitivity and specificity were 0.72 (0.71-0.74) and 0.47 (0.45-0.49) in men and 0.77 (0.75-0.78) and 0.50 (0.48-0.52) in women, respectively. Addition of fasting plasma glucose (FPG) to the model improved the prediction slightly [AROC curve 0.70 (0.65-0.76) in men, 0.71 (0.67-0.76) in women]. CONCLUSIONS: A diabetes prediction model based on obesity and family history yielded moderate discrimination in Mauritian Indians, which was slightly inferior to the model with the FPG but may be useful in low-income countries to promote identification of people at high risk of diabetes.
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| 4. |
- Marroni, Fabio, et al.
(författare)
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A genome-wide association scan of RR and QT interval duration in 3 European genetically isolated populations : the EUROSPAN project
- 2009
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Ingår i: Circulation: Cardiovascular Genetics. - 1942-3268. ; 2:4, s. 322-328
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We set out to identify common genetic determinants of the length of the RR and QT intervals in 2325 individuals from isolated European populations. METHODS AND RESULTS: We analyzed the heart rate at rest, measured as the RR interval, and the length of the corrected QT interval for association with 318 237 single-nucleotide polymorphisms. The RR interval was associated with common variants within GPR133, a G-protein-coupled receptor (rs885389, P=3.9 x 10(-8)). The QT interval was associated with the earlier reported NOS1AP gene (rs2880058, P=2.00 x 10(-10)) and with a region on chromosome 13 (rs2478333, P=4.34 x 10(-8)), which is 100 kb from the closest known transcript LOC730174 and has previously not been associated with the length of the QT interval. CONCLUSIONS: Our results suggested an association between the RR interval and GPR133 and confirmed an association between the QT interval and NOS1AP.
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| 6. |
- Dalrymple, Annette, et al.
(författare)
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Proteomic profiling of plasma in Huntington's disease reveals neuroinflammatory activation and biomarker candidates
- 2007
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 6:7, s. 2833-2840
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Tidskriftsartikel (refereegranskat)abstract
- Huntington's disease (HD) causes widespread CNS changes and systemic abnormalities including endocrine and immune dysfunction. HD biomarkers are needed to power clinical trials of potential treatments. We used multiplatform proteomic profiling to reveal plasma changes with HD progression. Proteins of interest were evaluated using immunoblotting and ELISA in plasma from 2 populations, CSF and R6/2 mice. The identified proteins demonstrate neuroinflammation in HD and warrant further investigation as possible biomarkers.
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| 8. |
- Hicks, Andrew A., et al.
(författare)
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Genetic determinants of circulating sphingolipid concentrations in European populations
- 2009
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Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 5:10, s. e1000672-
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Tidskriftsartikel (refereegranskat)abstract
- Sphingolipids have essential roles as structural components of cell membranes and in cell signalling, and disruption of their metabolism causes several diseases, with diverse neurological, psychiatric, and metabolic consequences. Increasingly, variants within a few of the genes that encode enzymes involved in sphingolipid metabolism are being associated with complex disease phenotypes. Direct experimental evidence supports a role of specific sphingolipid species in several common complex chronic disease processes including atherosclerotic plaque formation, myocardial infarction (MI), cardiomyopathy, pancreatic β-cell failure, insulin resistance, and type 2 diabetes mellitus. Therefore, sphingolipids represent novel and important intermediate phenotypes for genetic analysis, yet little is known about the major genetic variants that influence their circulating levels in the general population. We performed a genome-wide association study (GWAS) between 318,237 single-nucleotide polymorphisms (SNPs) and levels of circulating sphingomyelin (SM), dihydrosphingomyelin (Dih-SM), ceramide (Cer), and glucosylceramide (GluCer) single lipid species (33 traits); and 43 matched metabolite ratios measured in 4,400 subjects from five diverse European populations. Associated variants (32) in five genomic regions were identified with genome-wide significant corrected p-values ranging down to 9.08×10−66. The strongest associations were observed in or near 7 genes functionally involved in ceramide biosynthesis and trafficking: SPTLC3, LASS4, SGPP1, ATP10D, and FADS1–3. Variants in 3 loci (ATP10D, FADS3, and SPTLC3) associate with MI in a series of three German MI studies. An additional 70 variants across 23 candidate genes involved in sphingolipid-metabolizing pathways also demonstrate association (p = 10−4 or less). Circulating concentrations of several key components in sphingolipid metabolism are thus under strong genetic control, and variants in these loci can be tested for a role in the development of common cardiovascular, metabolic, neurological, and psychiatric diseases.
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