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| 15. |
- Madden, Stephen F., et al.
(författare)
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Detecting microRNA activity from gene expression data
- 2010
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Ingår i: BMC Bioinformatics. - : Springer Science and Business Media LLC. - 1471-2105. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Background: MicroRNAs (miRNAs) are non-coding RNAs that regulate gene expression by binding to the messenger RNA (mRNA) of protein coding genes. They control gene expression by either inhibiting translation or inducing mRNA degradation. A number of computational techniques have been developed to identify the targets of miRNAs. In this study we used predicted miRNA-gene interactions to analyse mRNA gene expression microarray data to predict miRNAs associated with particular diseases or conditions. Results: Here we combine correspondence analysis, between group analysis and co-inertia analysis (CIA) to determine which miRNAs are associated with differences in gene expression levels in microarray data sets. Using a database of miRNA target predictions from TargetScan, TargetScanS, PicTar4way PicTar5way, and miRanda and combining these data with gene expression levels from sets of microarrays, this method produces a ranked list of miRNAs associated with a specified split in samples. We applied this to three different microarray datasets, a papillary thyroid carcinoma dataset, an in-house dataset of lipopolysaccharide treated mouse macrophages, and a multi-tissue dataset. In each case we were able to identified miRNAs of biological importance. Conclusions: We describe a technique to integrate gene expression data and miRNA target predictions from multiple sources.
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| 16. |
- Teyssier, D., et al.
(författare)
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Herschel/HIFI In-flight commissioning and performance
- 2010
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Ingår i: 21st International Symposium on Space Terahertz Technology 2010, ISSTT 2010; Oxford; United Kingdom; 23 March 2010 through 25 March 2010. - 9781617823626 ; , s. 23-28
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Konferensbidrag (refereegranskat)abstract
- The Herschel Space Observatory was successfully launched on the 14th of May, 2009, lifting into space the Heterodyne Instrument for the Far-Infrared (HIFI). After the standard early orbit operations on the Space-craft, the instrument was switched on for the first time on the 24th of May, kicking off an instrument Commissioning period of more than a month and a half. We present here the outcome of this Commissioning campaign, including the measured in-flight performance of the instrument. Among the challenges encountered during this period was the need to optimize the stability of the signal provided by the Local Oscillator (LO) chains in some of the frequency bands, in particular that covering the singly Ionized Carbon (C+) line at the upper edge of the HIFI range, and one of the backbones of the science program of the instrument. The same concept also allowed significant improvements in the upper end of the 3b LO chain. Another noticeable achievement was the very good co-alignment measured between the mixer beams in the respective H and V polarizations offered by HIFI, allowing for more than a simple build-in redundancy, as the observing efficiency will really benefits from the combination of the two mixers.
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| 17. |
- Veroniki, A. A., et al.
(författare)
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Evaluation of inconsistency in networks of interventions
- 2013
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Ingår i: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 42:1, s. 332-345
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Tidskriftsartikel (refereegranskat)abstract
- Background The assumption of consistency, defined as agreement between direct and indirect Methods In this paper we assess the prevalence of inconsistency from data of 40 published networks of Results Inconsistency was detected in from 2% to 9% of the tested loops, depending on the effect Conclusions The study suggests that changing the effect measure might improve statistical consistency
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| 19. |
- Higgins, Larry G., et al.
(författare)
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Conditional Expression of Human PPAR delta and a Dominant Negative Variant of hPPAR delta In Vivo
- 2012
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Ingår i: PPAR Research. - : Hindawi Limited. - 1687-4757 .- 1687-4765.
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Tidskriftsartikel (refereegranskat)abstract
- The nuclear receptor, NR1C2 or peroxisome proliferator-activated receptor (PPAR)-delta, is ubiquitously expressed and important for placental development, fatty acid metabolism, wound healing, inflammation, and tumour development. PPAR delta has been hypothesized to function as both a ligand activated transcription factor and a repressor of transcription in the absence of agonist. In this paper, treatment of mice conditionally expressing human PPAR delta with GW501516 resulted in a marked loss in body weight that was not evident in nontransgenic animals or animals expressing a dominant negative derivative of PPAR delta. Expression of either functional or dominant negative hPPAR delta blocked bezafibrate-induced PPAR alpha-dependent hepatomegaly and blocked the effect of bezafibrate on the transcription of PPAR alpha target genes. These data demonstrate, for the first time, that PPAR delta could inhibit the activation of PPAR alpha in vivo and provide novel models for the investigation of the role of PPAR delta in pathophysiology.
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| 20. |
- Jaiswal, Siddhartha, et al.
(författare)
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Age-Related Clonal Hematopoiesis Associated with Adverse Outcomes.
- 2014
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Ingår i: New England Journal of Medicine. - 0028-4793. ; 371:26, s. 2488-2498
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Tidskriftsartikel (refereegranskat)abstract
- Background The incidence of hematologic cancers increases with age. These cancers are associated with recurrent somatic mutations in specific genes. We hypothesized that such mutations would be detectable in the blood of some persons who are not known to have hematologic disorders. Methods We analyzed whole-exome sequencing data from DNA in the peripheral-blood cells of 17,182 persons who were unselected for hematologic phenotypes. We looked for somatic mutations by identifying previously characterized single-nucleotide variants and small insertions or deletions in 160 genes that are recurrently mutated in hematologic cancers. The presence of mutations was analyzed for an association with hematologic phenotypes, survival, and cardiovascular events. Results Detectable somatic mutations were rare in persons younger than 40 years of age but rose appreciably in frequency with age. Among persons 70 to 79 years of age, 80 to 89 years of age, and 90 to 108 years of age, these clonal mutations were observed in 9.5% (219 of 2300 persons), 11.7% (37 of 317), and 18.4% (19 of 103), respectively. The majority of the variants occurred in three genes: DNMT3A, TET2, and ASXL1. The presence of a somatic mutation was associated with an increase in the risk of hematologic cancer (hazard ratio, 11.1; 95% confidence interval [CI], 3.9 to 32.6), an increase in all-cause mortality (hazard ratio, 1.4; 95% CI, 1.1 to 1.8), and increases in the risks of incident coronary heart disease (hazard ratio, 2.0; 95% CI, 1.2 to 3.4) and ischemic stroke (hazard ratio, 2.6; 95% CI, 1.4 to 4.8). Conclusions Age-related clonal hematopoiesis is a common condition that is associated with increases in the risk of hematologic cancer and in all-cause mortality, with the latter possibly due to an increased risk of cardiovascular disease. (Funded by the National Institutes of Health and others.).
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