| 1. |
- Craddock, Nick, et al.
(författare)
-
Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls
- 2010
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7289, s. 713-720
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Tidskriftsartikel (refereegranskat)abstract
- Copy number variants (CNVs) account for a major proportion of human genetic polymorphism and have been predicted to have an important role in genetic susceptibility to common disease. To address this we undertook a large, direct genome-wide study of association between CNVs and eight common human diseases. Using a purpose-designed array we typed,19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated similar to 50% of all common CNVs larger than 500 base pairs. We identified several biological artefacts that lead to false-positive associations, including systematic CNV differences between DNAs derived from blood and cell lines. Association testing and follow-up replication analyses confirmed three loci where CNVs were associated with disease-IRGM for Crohn's disease, HLA for Crohn's disease, rheumatoid arthritis and type 1 diabetes, and TSPAN8 for type 2 diabetes-although in each case the locus had previously been identified in single nucleotide polymorphism (SNP)-based studies, reflecting our observation that most common CNVs that are well-typed on our array are well tagged by SNPs and so have been indirectly explored through SNP studies. We conclude that common CNVs that can be typed on existing platforms are unlikely to contribute greatly to the genetic basis of common human diseases.
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| 2. |
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| 3. |
- Beecham, Ashley H, et al.
(författare)
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Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis.
- 2013
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:11, s. 1353-60
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Tidskriftsartikel (refereegranskat)abstract
- Using the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (P < 1.0 × 10(-4)). In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 subjects with multiple sclerosis and 26,703 healthy controls. In these 80,094 individuals of European ancestry, we identified 48 new susceptibility variants (P < 5.0 × 10(-8)), 3 of which we found after conditioning on previously identified variants. Thus, there are now 110 established multiple sclerosis risk variants at 103 discrete loci outside of the major histocompatibility complex. With high-resolution Bayesian fine mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association. This study enhances the catalog of multiple sclerosis risk variants and illustrates the value of fine mapping in the resolution of GWAS signals.
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| 4. |
- Polyak, Leonid, et al.
(författare)
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History of sea ice in the Arctic
- 2010
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Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 29:15-16, s. 1757-1778
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Tidskriftsartikel (refereegranskat)abstract
- Arctic sea-ice extent and volume are declining rapidly. Several studies project that the Arctic Ocean may become seasonally ice-free by the year 2040 or even earlier. Putting this into perspective requires information on the history of Arctic sea-ice conditions through the geologic past. This information can be provided by proxy records from the Arctic Ocean floor and from the surrounding coasts. Although existing records are far from complete, they indicate that sea ice became a feature of the Arctic by 47 Ma, following a pronounced decline in atmospheric pCO(2) after the Paleocene-Eocene Thermal Optimum, and consistently covered at least part of the Arctic Ocean for no less than the last 13-14 million years. Ice was apparently most widespread during the last 2-3 million years, in accordance with Earth's overall cooler climate. Nevertheless, episodes of considerably reduced sea ice or even seasonally ice-free conditions occurred during warmer periods linked to orbital variations. The last low-ice event related to orbital forcing (high insolation) was in the early Holocene, after which the northern high latitudes cooled overall, with some superimposed shorterterm (multidecadal to millennial-scale) and lower-magnitude variability. The current reduction in Arctic ice cover started in the late 19th century, consistent with the rapidly warming climate, and became very pronounced over the last three decades. This ice loss appears to be unmatched over at least the last few thousand years and unexplainable by any of the known natural variabilities.
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| 5. |
- Scott, Robert A., et al.
(författare)
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Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways
- 2012
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:9, s. 991-1005
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Tidskriftsartikel (refereegranskat)abstract
- Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have increased the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes risk (q < 0.05). Loci influencing fasting insulin concentration showed association with lipid levels and fat distribution, suggesting impact on insulin resistance. Gene-based analyses identified further biologically plausible loci, suggesting that additional loci beyond those reaching genome-wide significance are likely to represent real associations. This conclusion is supported by an excess of directionally consistent and nominally significant signals between discovery and follow-up studies. Functional analysis of these newly discovered loci will further improve our understanding of glycemic control.
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| 6. |
- Adare, A., et al.
(författare)
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Cold-Nuclear-Matter Effects on Heavy-Quark Production at Forward and Backward Rapidity in d + Au Collisions at root s(NN) = GeV
- 2014
-
Ingår i: Physical Review Letters. - 1079-7114. ; 112:25
-
Tidskriftsartikel (refereegranskat)abstract
- The PHENIX experiment has measured open heavy-flavor production via semileptonic decay over the transverse momentum range 1 < p(T) < 6 GeV/c at forward and backward rapidity (1.4 < vertical bar y vertical bar < 2.0) in d + Au and p + p collisions at root s(NN) = 200 GeV. In central d + Au collisions, relative to the yield in p + p collisions scaled by the number of binary nucleon-nucleon collisions, a suppression is observed at forward rapidity (in the d-going direction) and an enhancement at backward rapidity (in the Au-going direction). Predictions using nuclear-modified-parton-distribution functions, even with additional nuclear-p(T) broadening, cannot simultaneously reproduce the data at both rapidity ranges, which implies that these models are incomplete and suggests the possible importance of final-state interactions in the asymmetric d + Au collision system. These results can be used to probe cold-nuclear-matter effects, which may significantly affect heavy-quark production, in addition to helping constrain the magnitude of charmonia-breakup effects in nuclear matter.
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| 7. |
- Adare, A., et al.
(författare)
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Double-spin asymmetry of electrons from heavy-flavor decays in p plus p collisions at root s=200 GeV
- 2013
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Ingår i: Physical Review D (Particles, Fields, Gravitation and Cosmology). - 1550-2368. ; 87:1
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Tidskriftsartikel (refereegranskat)abstract
- We report on the first measurement of the double-spin asymmetry, A(LL), of electrons from the decays of hadrons containing heavy flavor in longitudinally polarized p + p collisions at root s = 200 GeV for p(T) = 0.5 to 3.0 GeV/c. The asymmetry was measured at midrapidity (vertical bar eta vertical bar < 0.35) with the PHENIX detector at the Relativistic Heavy Ion Collider. The measured asymmetries are consistent with zero within the statistical errors. We obtained a constraint for the polarized gluon distribution in the proton of vertical bar Delta g/g(log(10)(x) = -1.6(-0.4)(+0.5), mu = m(T)(c)vertical bar(2) < 0.030 (1 sigma) based on a leading-order perturbative quantum chromodynamics model, using the measured asymmetry. DOI: 10.1103/PhysRevD.87.012011
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| 8. |
- Adare, A., et al.
(författare)
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gamma (1S+2S+3S) production in d plus Au and p plus p collisions at root s(NN)=200 GeV and cold-nuclear-matter effects
- 2013
-
Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 87:4
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Tidskriftsartikel (refereegranskat)abstract
- The three gamma states, gamma (1S + 2S + 3S), are measured in d + Au and p + p collisions at root s(NN) = 200 GeV and rapidities 1.2 < vertical bar y vertical bar < 2.2 by the PHENIX experiment at the Relativistic Heavy Ion Collider. Cross sections for the inclusive gamma (1S + 2S + 3S) production are obtained. The inclusive yields per binary collision for d + Au collisions relative to those in p + p collisions (R-dAu) are found to be 0.62 +/- 0.26 (stat) +/- 0.13 (syst) in the gold-going direction and 0.91 +/- 0.33 (stat) +/- 0.16 (syst) in the deuteron-going direction. The measured results are compared to a nuclear-shadowing model, EPS09 [Eskola et al., J. High Energy Phys. 04 (2009) 065], combined with a final-state breakup cross section, sigma(br), and compared to lower energy p + A results. We also compare the results to the PHENIX J/psi results [Adare et al., Phys. Rev. Lett. 107, 142301 (2011)]. The rapidity dependence of the observed gamma suppression is consistent with lower energy p + A measurements. DOI: 10.1103/PhysRevC.87.044909
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| 9. |
- Adare, A., et al.
(författare)
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Inclusive double-helicity asymmetries in neutral-pion and eta-meson production in + collisions at root s=200 GeV
- 2014
-
Ingår i: Physical Review D (Particles, Fields, Gravitation and Cosmology). - 1550-2368. ; 90:1
-
Tidskriftsartikel (refereegranskat)abstract
- Results are presented from data recorded in 2009 by the PHENIX experiment at the Relativistic Heavy Ion Collider for the double-longitudinal spin asymmetry, A(LL), for pi(0) and eta production in root s = 200 GeV polarized p + p collisions. Comparison of the pi(0) results with different theory expectations based on fits of other published data showed a preference for small positive values of gluon polarization, Delta G, in the proton in the probed Bjorken x range. The effect of adding the new 2009 pi(0) data to a recent global analysis of polarized scattering data is also shown, resulting in a best fit Delta G(DSSV)([0.05,0.2]) = 0.06(-0.15)(+0.11) in the range 0.05 < x < 0.2, with the uncertainty at Delta chi(2) = 9 when considering only statistical experimental uncertainties. Shifting the PHENIX data points by their systematic uncertainty leads to a variation of the best-fit value of Delta G(DSSV)([0.05,0.2]) between 0.02 and 0.12, demonstrating the need for full treatment of the experimental systematic uncertainties in future global analyses.
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| 10. |
- Adare, A., et al.
(författare)
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Low-mass vector-meson production at forward rapidity in p plus p collisions at root s=200 GeV
- 2014
-
Ingår i: Physical Review D (Particles, Fields, Gravitation and Cosmology). - 1550-2368. ; 90:5
-
Tidskriftsartikel (refereegranskat)abstract
- The PHENIX experiment at the Relativistic Heavy Ion Collider has measured low-mass vector-meson ,omega, rho, and phi, production through the dimuon decay channel at forward rapidity (1.2 < vertical bar y vertical bar < 2.2) in p + p collisions at root s = 200 GeV. The differential cross sections for these mesons are measured as a function of both p(T) and rapidity. We also report the integrated differential cross sections over 1 < p(T) < 7 GeV/c and 1.2 < vertical bar y vertical bar < 2.2: d sigma/dy(omega + rho rho -> mu mu) = 80 +/- 6(stat) +/- 12(syst)nb and d sigma/dy(phi -> mu mu) = 27 +/- 3(stat) +/- 4(syst)nb. These results are compared with midrapidity measurements and calculations.
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| 11. |
- Callaghan, Terry, et al.
(författare)
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Multi-Decadal Changes in Tundra Environments and Ecosystems : Synthesis of the International Polar Year-Back to the Future Project (IPY-BTF)
- 2011
-
Ingår i: Ambio. - : Springer Science and Business Media LLC. - 0044-7447 .- 1654-7209. ; 40:6, s. 705-716
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Tidskriftsartikel (refereegranskat)abstract
- Understanding the responses of tundra systemsto global change has global implications. Most tundraregions lack sustained environmental monitoring and oneof the only ways to document multi-decadal change is toresample historic research sites. The International PolarYear (IPY) provided a unique opportunity for such researchthrough the Back to the Future (BTF) project (IPY project#512). This article synthesizes the results from 13 paperswithin this Ambio Special Issue. Abiotic changes includeglacial recession in the Altai Mountains, Russia; increasedsnow depth and hardness, permafrost warming, andincreased growing season length in sub-arctic Sweden;drying of ponds in Greenland; increased nutrient availabilityin Alaskan tundra ponds, and warming at mostlocations studied. Biotic changes ranged from relativelyminor plant community change at two sites in Greenland tomoderate change in the Yukon, and to dramatic increasesin shrub and tree density on Herschel Island, and in subarcticSweden. The population of geese tripled at one sitein northeast Greenland where biomass in non-grazed plotsdoubled. A model parameterized using results from a BTFstudy forecasts substantial declines in all snowbeds andincreases in shrub tundra on Niwot Ridge, Colorado overthe next century. In general, results support and provideimproved capacities for validating experimental manipulation,remote sensing, and modeling studies.
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| 12. |
- Conrad, Donald F., et al.
(författare)
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Origins and functional impact of copy number variation in the human genome
- 2010
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7289, s. 704-712
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Tidskriftsartikel (refereegranskat)abstract
- Structural variations of DNA greater than 1 kilobase in size account for most bases that vary among human genomes, but are still relatively under-ascertained. Here we use tiling oligonucleotide microarrays, comprising 42 million probes, to generate a comprehensive map of 11,700 copy number variations (CNVs) greater than 443 base pairs, of which most (8,599) have been validated independently. For 4,978 of these CNVs, we generated reference genotypes from 450 individuals of European, African or East Asian ancestry. The predominant mutational mechanisms differ among CNV size classes. Retrotransposition has duplicated and inserted some coding and non-coding DNA segments randomly around the genome. Furthermore, by correlation with known trait-associated single nucleotide polymorphisms (SNPs), we identified 30 loci with CNVs that are candidates for influencing disease susceptibility. Despite this, having assessed the completeness of our map and the patterns of linkage disequilibrium between CNVs and SNPs, we conclude that, for complex traits, the heritability void left by genome-wide association studies will not be accounted for by common CNVs.
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| 13. |
- Ding, Yuan C, et al.
(författare)
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A nonsynonymous polymorphism in IRS1 modifies risk of developing breast and ovarian cancers in BRCA1 and ovarian cancer in BRCA2 mutation carriers
- 2012
-
Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 21:8, s. 1362-1370
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We previously reported significant associations between genetic variants in insulin receptor substrate 1 (IRS1) and breast cancer risk in women carrying BRCA1 mutations. The objectives of this study were to investigate whether the IRS1 variants modified ovarian cancer risk and were associated with breast cancer risk in a larger cohort of BRCA1 and BRCA2 mutation carriers.METHODS: IRS1 rs1801123, rs1330645, and rs1801278 were genotyped in samples from 36 centers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Data were analyzed by a retrospective cohort approach modeling the associations with breast and ovarian cancer risks simultaneously. Analyses were stratified by BRCA1 and BRCA2 status and mutation class in BRCA1 carriers.RESULTS: Rs1801278 (Gly972Arg) was associated with ovarian cancer risk for both BRCA1 (HR, 1.43; 95% confidence interval (CI), 1.06-1.92; P = 0.019) and BRCA2 mutation carriers (HR, 2.21; 95% CI, 1.39-3.52, P = 0.0008). For BRCA1 mutation carriers, the breast cancer risk was higher in carriers with class II mutations than class I mutations (class II HR, 1.86; 95% CI, 1.28-2.70; class I HR, 0.86; 95%CI, 0.69-1.09; P(difference), 0.0006). Rs13306465 was associated with ovarian cancer risk in BRCA1 class II mutation carriers (HR, 2.42; P = 0.03).CONCLUSION: The IRS1 Gly972Arg single-nucleotide polymorphism, which affects insulin-like growth factor and insulin signaling, modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers and breast cancer risk in BRCA1 class II mutation carriers.Impact: These findings may prove useful for risk prediction for breast and ovarian cancers in BRCA1 and BRCA2 mutation carriers.
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| 14. |
- Elmegreen, Debra Meloy, et al.
(författare)
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HIERARCHICAL STAR FORMATION IN NEARBY LEGUS GALAXIES
- 2014
-
Ingår i: Astrophysical Journal Letters. - 2041-8205. ; 787:1, s. L15-
-
Tidskriftsartikel (refereegranskat)abstract
- Hierarchical structure in ultraviolet images of 12 late-type LEGUS galaxies is studied by determining the numbers and fluxes of nested regions as a function of size from similar to 1 to similar to 200 pc, and the number as a function of flux. Two starburst dwarfs, NGC 1705 and NGC 5253, have steeper number-size and flux-size distributions than the others, indicating high fractions of the projected areas filled with star formation. Nine subregions in seven galaxies have similarly steep number-size slopes, even when the whole galaxies have shallower slopes. The results suggest that hierarchically structured star-forming regions several hundred parsecs or larger represent common unit structures. Small galaxies dominated by only a few of these units tend to be starbursts. The self-similarity of young stellar structures down to parsec scales suggests that star clusters form in the densest parts of a turbulent medium that also forms loose stellar groupings on larger scales. The presence of super star clusters in two of our starburst dwarfs would follow from the observed structure if cloud and stellar subregions more readily coalesce when self-gravity in the unit cell contributes more to the total gravitational potential.
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| 15. |
- Heap, Graham A., et al.
(författare)
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HLA-DQA1-HLA-DRB1 variants confer susceptibility to pancreatitis induced by thiopurine immunosuppressants
- 2014
-
Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 46:10, s. 1131-1134
-
Tidskriftsartikel (refereegranskat)abstract
- Pancreatitis occurs in approximately 4% of patients treated with the thiopurines azathioprine or mercaptopurine. Its development is unpredictable and almost always leads to drug withdrawal. We identified patients with inflammatory bowel disease (IBD) who had developed pancreatitis within 3 months of starting these drugs from 168 sites around the world. After detailed case adjudication, we performed a genome-wide association study on 172 cases and 2,035 controls with IBD. We identified strong evidence of association within the class II HLA region, with the most significant association identified at rs2647087 (odds ratio 2.59, 95% confidence interval 2.07-3.26, P = 2 x 10(-16)). We replicated these findings in an independent set of 78 cases and 472 controls with IBD matched for drug exposure. Fine mapping of the H LA region identified association with the HLA-DQA1*02:01-HLA-DRB1*07:01 haplotype. Patients heterozygous at rs2647087 have a 9% risk of developing pancreatitis after administration of a thiopurine, whereas homozygotes have a 17% risk.
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| 16. |
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| 17. |
- Kyösti, Petter, et al.
(författare)
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Simulation of industrial support systems in the context of functional products
- 2011
-
Ingår i: Proceedings of the 19th AR2TS Advances in Risk and Reliability Technology Symposium. - Nottingham : University of Nottingham. ; , s. 275-288
-
Konferensbidrag (refereegranskat)abstract
- Functional Products, consisting of hardware and service support systems owned by the supplier, are sold to customers with a guaranteed availability of the function. The availability achieved is dependent on the reliability of both hardware and the service support system. The reliability of the latter can be defined as its ability to provide the required maintenance services in a timely manner. This paper reports simulation of a service support system from an industrial case study in order to predict its reliability. To identify and develop a suitable case together with an industrial partner company, a number of phone meetings were held in order to explain the research question, interview knowledgeable people and plan on-site visits and interviews. A number of interviews face to face were carried out with the industrial partners, where the goal was to obtain enough information to be able to model the support system correctly. The research involved both qualitative information gathering and applied computer aided simulation. An improved model for simulating a service support system is developed that considers the context in which the maintenance procedures are performed within a Functional Product. A software implementation of the model, developed by the authors, is applied to simulate the case study service support system in various scenarios such as different personnel availability and number of systems supported. The results show how the modeling can be used to improve and predict the reliability of the service support system
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| 18. |
- Lekman, Magnus, et al.
(författare)
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The genetic interacting landscape of 63 candidate genes in Major Depressive Disorder : an explorative study
- 2014
-
Ingår i: BioData Mining. - : Springer Science and Business Media LLC. - 1756-0381. ; 7, s. 19-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Genetic contributions to major depressive disorder (MDD) are thought to result from multiple genes interacting with each other. Different procedures have been proposed to detect such interactions. Which approach is best for explaining the risk of developing disease is unclear. This study sought to elucidate the genetic interaction landscape in candidate genes for MDD by conducting a SNP-SNP interaction analysis using an exhaustive search through 3,704 SNP-markers in 1,732 cases and 1,783 controls provided from the GAIN MDD study. We used three different methods to detect interactions, two logistic regressions models (multiplicative and additive) and one data mining and machine learning (MDR) approach. Results: Although none of the interaction survived correction for multiple comparisons, the results provide important information for future genetic interaction studies in complex disorders. Among the 0.5% most significant observations, none had been reported previously for risk to MDD. Within this group of interactions, less than 0.03% would have been detectable based on main effect approach or an a priori algorithm. We evaluated correlations among the three different models and conclude that all three algorithms detected the same interactions to a low degree. Although the top interactions had a surprisingly large effect size for MDD (e. g. additive dominant model P-uncorrected = 9.10E-9 with attributable proportion (AP) value = 0.58 and multiplicative recessive model with P-uncorrected = 6.95E-5 with odds ratio (OR estimated from beta 3) value = 4.99) the area under the curve (AUC) estimates were low (< 0.54). Moreover, the population attributable fraction (PAF) estimates were also low (< 0.15). Conclusions: We conclude that the top interactions on their own did not explain much of the genetic variance of MDD. The different statistical interaction methods we used in the present study did not identify the same pairs of interacting markers. Genetic interaction studies may uncover previously unsuspected effects that could provide novel insights into MDD risk, but much larger sample sizes are needed before this strategy can be powerfully applied.
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| 19. |
- Löfstrand, Magnus, 1974-, et al.
(författare)
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Functional product system availability : simulation-driven design and operation through coupled multi-objective optimisation
- 2011
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Ingår i: International Journal of Product Development. - Bucks, United Kingdom : InderScience Publishers. - 1477-9056 .- 1741-8178. ; 13:2, s. 119-131
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Tidskriftsartikel (refereegranskat)abstract
- This paper describes on a conceptual level how the availability of functional products (consisting of hardware (HW) and a support system) may be simulated. The main objective of this paper is to present a simulation-driven methodology for predicting and optimising the availability and cost of functional products in both development and operation. The proposed simulation and optimisation methodology includes both HW and support system models, which coupled form a simulation model of a system (functional product) delivering the function. Two different simulation-driven methodologies are suggested in the paper: one for development and another for operation of functional products
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| 20. |
- Löfstrand, Magnus, 1974-, et al.
(författare)
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Modelling and simulation of functional product system availability and support costs
- 2012
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Ingår i: International Journal of Product Development. - Bucks, United Kingdom : InderScience Publishers. - 1477-9056 .- 1741-8178. ; 16:3-4, s. 304-325
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Functional products (FP), total offers or product service systems, that comprise of both hardware (HW) and support services (SS) sold as an integrated offering under an availability guarantee, are becoming increasing popular in industry. This paper addresses, through modelling and simulation, the challenge faced by suppliers in developing an integrated HW and SS design to produce an FP which meets contracted availability. A recently published framework specified how an integrated model hardware and service support system model could be used to obtain functional availability predictions and perform simulation driven functional product development. This paper presents the first example of an integrated functional product model. It uses fault tree, Petri net and discrete event simulation techniques to enable the prediction of functional product availability and support costs. Such predictions are used here to evaluate and compare different service support system designs.
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| 21. |
- Reed, Sean, et al.
(författare)
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A modelling language for maintenance task scheduling
- 2012
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Ingår i: 11th International Probabilistic Safety Assessment and Management Conference and the Annual European Safety and Reliability Conference 2012. - New York : Curran Associates, Inc.. - 9781622764365 ; , s. 201-211
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Konferensbidrag (refereegranskat)abstract
- This paper presents a modelling language for representing the details necessary to analyse and model the implementation of maintenance strategies for generic hardware. The maintenance strategy determines which, and when, restorations and inspections should take place whilst the scheduling of maintenance tasks implements these goals. The manner of maintenance strategy implementation therefore has important implications for maintenance cost and other performance metrics. Despite this, maintenance strategy optimisation models found in the literature lack detailed maintenance implementation models, which may lead to inaccurate and misleading results. The presented modelling language permits the representation of all common constraints and outcomes between maintenance tasks that influence task schedules. In doing so, it provides a platform for the future development of maintenance task schedule modelling, planning and decision support tools. The modelling language is demonstrated through application to part of a car braking system
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| 22. |
- Reed, Sean, et al.
(författare)
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A modelling language for maintenance task scheduling
- 2012
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Ingår i: 11th International Probabilistic Safety Assessment and Management Conference and the Annual European Safety and Reliability Conference 2012. - New York : Curran Associates, Inc.. - 9781622764365 ; , s. 201-211
-
Konferensbidrag (refereegranskat)abstract
- This paper presents a modelling language for representing the details necessary to analyse and model the implementation of maintenance strategies for generic hardware. The maintenance strategy determines which, and when, restorations and inspections should take place whilst the scheduling of maintenance tasks implements these goals. The manner of maintenance strategy implementation therefore has important implications for maintenance cost and other performance metrics. Despite this, maintenance strategy optimisation models found in the literature lack detailed maintenance implementation models, which may lead to inaccurate and misleading results. The presented modelling language permits the representation of all common constraints and outcomes between maintenance tasks that influence task schedules. In doing so, it provides a platform for the future development of maintenance task schedule modelling, planning and decision support tools. The modelling language is demonstrated through application to part of a car braking system.
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| 23. |
- Reed, Sean, 1982-, et al.
(författare)
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Improved efficiency in the analysis of phased mission systems with multiple failure mode components
- 2011
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Ingår i: IEEE Transactions on Reliability. - : IEEE. - 0018-9529 .- 1558-1721. ; 60:1, s. 70-79
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Tidskriftsartikel (refereegranskat)abstract
- Systems often operate in phased missions where their reliability structure varies over a set of consecutive time periods, known as phases. The reliability of a phased mission is defined as the probability that all phases in the mission are completed without failure. While the Binary Decision Diagram (BDD) method has been shown to be the most efficient solution for measuring the reliability of phased missions with non-repairable components with mutually exclusive failure modes, the existing BDD based methods are still unable to analyze large systems without considerable computational expense. This paper introduces a new BDD based method that is shown to provide improved efficiency and accuracy in the repeat analysis of this type of phased mission.
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| 24. |
- Reed, Sean, et al.
(författare)
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Modelling service support system reliability
- 2011
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Ingår i: First IFAC Workshop on Advanced Maintenance Engineering, Services and Technology (2010). - Red Hook, NY : IFAC, International Federation of Automatic Control. - 9783902661784 ; , s. 56-61
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Konferensbidrag (refereegranskat)
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| 25. |
- Reed, Sean, et al.
(författare)
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Modelling service support system reliability
- 2010
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Functional Products, where the customer pays for the function and availability of a product instead of the product itself, are increasingly popular in capital intensive industries such as aerospace. Such products are integrated systems involving the combination of hardware and service support systems. The reliability prediction and optimisation of the service system that supports the hardware availability is essential to the feasibility of the product. These systems consist of maintenance procedures and resource provisions. Simulation based techniques are presented in this paper to analyse the reliability of support systems and their application is demonstrated through a simple example.
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| 26. |
- Reed, Sean, 1982-, et al.
(författare)
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Service support system modelling language for simulation-driven development of functional products
- 2013
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Ingår i: 2nd International Through-life Engineering Services Conference. - : Elsevier. ; 11, s. 420-424
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Konferensbidrag (refereegranskat)abstract
- A functional product (FP) comprises of an integrated package of hardware and support services sold under a performance-based contract. A barrier to the adoption of FP is the lack of tools for obtaining predictions of availability and support costs during product development. A previous paper by the authors described a simulation-driven development strategy for designing FP that are optimised for functional availability and support costs. This iterative strategy involves representing the FP design in a modelling language; using a software code to automatically generate and analyse a simulation model from this representation to produce detailed performance predictions; and using these predictions as feedback to improve the design. The use of a modelling language facilitates the representation of the design details within the hardware and support system that influence availability and support costs. This includes the maintenance process design, maintenance strategy design and maintenance resource availability design. In this paper, an overview of a modelling language the authors have developed for this purpose is described.
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- Roy, Sushmita, et al.
(författare)
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Identification of functional elements and regulatory circuits by Drosophila modENCODE.
- 2010
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Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 330:6012, s. 1787-1797
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Tidskriftsartikel (refereegranskat)abstract
- To gain insight into how genomic information is translated into cellular and developmental programs, the Drosophila model organism Encyclopedia of DNA Elements (modENCODE) project is comprehensively mapping transcripts, histone modifications, chromosomal proteins, transcription factors, replication proteins and intermediates, and nucleosome properties across a developmental time course and in multiple cell lines. We have generated more than 700 data sets and discovered protein-coding, noncoding, RNA regulatory, replication, and chromatin elements, more than tripling the annotated portion of the Drosophila genome. Correlated activity patterns of these elements reveal a functional regulatory network, which predicts putative new functions for genes, reveals stage- and tissue-specific regulators, and enables gene-expression prediction. Our results provide a foundation for directed experimental and computational studies in Drosophila and related species and also a model for systematic data integration toward comprehensive genomic and functional annotation.
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