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- Carninci, P, et al.
(författare)
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The transcriptional landscape of the mammalian genome
- 2005
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Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 309:5740, s. 1559-1563
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Tidskriftsartikel (refereegranskat)abstract
- This study describes comprehensive polling of transcription start and termination sites and analysis of previously unidentified full-length complementary DNAs derived from the mouse genome. We identify the 5′ and 3′ boundaries of 181,047 transcripts with extensive variation in transcripts arising from alternative promoter usage, splicing, and polyadenylation. There are 16,247 new mouse protein-coding transcripts, including 5154 encoding previously unidentified proteins. Genomic mapping of the transcriptome reveals transcriptional forests, with overlapping transcription on both strands, separated by deserts in which few transcripts are observed. The data provide a comprehensive platform for the comparative analysis of mammalian transcriptional regulation in differentiation and development.
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- Cox, Angela, et al.
(författare)
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A common coding variant in CASP8 is associated with breast cancer risk
- 2007
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 39:3, s. 352-358
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Tidskriftsartikel (refereegranskat)abstract
- The Breast Cancer Association Consortium (BCAC) has been established to conduct combined case-control analyses with augmented statistical power to try to confirm putative genetic associations with breast cancer. We genotyped nine SNPs for which there was some prior evidence of an association with breast cancer: CASP8 D302H (rs1045485), IGFBP3 -202 C --> A (rs2854744), SOD2 V16A (rs1799725), TGFB1 L10P (rs1982073), ATM S49C (rs1800054), ADH1B 3' UTR A --> G (rs1042026), CDKN1A S31R (rs1801270), ICAM5 V301I (rs1056538) and NUMA1 A794G (rs3750913). We included data from 9-15 studies, comprising 11,391-18,290 cases and 14,753-22,670 controls. We found evidence of an association with breast cancer for CASP8 D302H (with odds ratios (OR) of 0.89 (95% confidence interval (c.i.): 0.85-0.94) and 0.74 (95% c.i.: 0.62-0.87) for heterozygotes and rare homozygotes, respectively, compared with common homozygotes; P(trend) = 1.1 x 10(-7)) and weaker evidence for TGFB1 L10P (OR = 1.07 (95% c.i.: 1.02-1.13) and 1.16 (95% c.i.: 1.08-1.25), respectively; P(trend) = 2.8 x 10(-5)). These results demonstrate that common breast cancer susceptibility alleles with small effects on risk can be identified, given sufficiently powerful studies.
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- Zelissen, P M J, et al.
(författare)
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Effect of three treatment schedules of recombinant methionyl human leptin on body weight in obese adults: a randomized, placebo-controlled trial.
- 2005
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Ingår i: Diabetes, obesity & metabolism. - : Wiley. - 1462-8902 .- 1463-1326. ; 7:6, s. 755-61
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Tidskriftsartikel (refereegranskat)abstract
- AIM: The aim of this study was to evaluate the effect on body weight and safety of subcutaneously administered recombinant leptin in obese adults and to evaluate whether the timing of recombinant leptin administration influences efficacy. METHODS: A randomized, double-blind, placebo-controlled, multicentre study was designed, comprising of a 3-week dietary lead-in followed by a 12-week leptin or placebo treatment period. A total of 284 overweight and obese (body mass index 27-37.0 kg/m(2)) predominantly white (98%) women (66%) and men (34%) with a mean (+/-s.d.) 46.8+/-10.4 years of age were randomized into three treatment groups with three matching placebo groups. Recombinant leptin was administered by subcutaneous injection [10 mg/morning, 10 mg/evening or 20 mg/day (10 mg twice daily)]. Patients were counselled at baseline to reduce dietary intake by 2,100 kJ/day (500 kcal/day), and dietary advice was reinforced every 2-4 weeks. RESULTS: No statistically significant change in body weight occurred with recombinant leptin treatment compared with placebo treatment in any treatment group. No clinically significant adverse effects were observed with the exception of an increase in injection-site reactions in patients treated with recombinant leptin (83%) vs. placebo (36%). CONCLUSIONS: Administration of recombinant leptin to an overweight and obese population, in addition to a mildly energy-restricted diet, was not efficacious in terms of weight loss at the doses and schedules studied. The hypothesis that nocturnal administration of recombinant leptin might have a specific effect on weight loss was not supported.
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- Jones, E. A., et al.
(författare)
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ToF-SIMS analysis of bio-systems: Are polyatomic primary ions the solution?
- 2006
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Ingår i: Applied Surface Science. - : Elsevier BV. - 0169-4332. ; 252:19, s. 6844-6854
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Konferensbidrag (refereegranskat)abstract
- We discuss the potential of cluster ion beams for overcoming difficulties experienced within molecular analysis in conventional static secondary ion mass spectrometry (SIMS). Consideration of secondary ion yield, surface damage and molecular depth profiling is included. Examples of the greatly increased secondary ion yields from 'real world' samples such as bacterial membranes are illustrated, the increase in information then benefiting multivariate analysis techniques such as principal component analysis (PCA). The increased efficiency of secondary ion formation with cluster beams, in conjunction with the reduced subsurface damage associated with C-60 bombardment is exemplified using a depth profile through a phospholipid layer, where molecular information is obtained even following doses of 2 x 10(15) ions/cm(2). This is developed further to the identification of molecular ions from the interior of etched cells. Challenges that cannot be solved solely by increased secondary ion yields and low sample damage have been considered and complications due to the influence of matrix effects along with the effect of salt concentration on the fate of molecular signals in depth profiles of biomaterials have been investigated. (c) 2006 Elsevier B.V. All rights reserved.
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- Lindberg, AL, et al.
(författare)
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Arsenic exposure in Hungary, Romania and Slovakia
- 2006
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Ingår i: Journal of environmental monitoring : JEM. - : Royal Society of Chemistry (RSC). - 1464-0325. ; 8:1, s. 203-208
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Tidskriftsartikel (refereegranskat)
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