| 1. |
- Andersson, Christian, et al.
(author)
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Derivative-free Parameter Optimization of Functional Mock-up Units
- 2012
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In: [Host publication title missing].
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Conference paper (peer-reviewed)abstract
- Representing a physical system with a mathematical model requires knowledge not only about the physical laws governing the dynamics but also about the parameter values of the system. The parameters can sometimes be measured or calculated, however some of them are often difficult or impossible to obtain in these ways. Finding accurate parameter values is crucial for the accuracy of the mathematical model. Estimating the parameters using optimization algorithms which attempt to minimize the error between the response from the mathematical model and the physical system is a common approach for improving the accuracy of the model. Optimization algorithms usually requires information about the derivatives which may not always be available or not be appropriate for estimation which forces the use of derivative-free optimization algorithms. In this paper, we present an implementation of derivative-free optimization algorithms for parameter estimation in the JModelica.org platform. The implementation allows the underlying dynamic system to be represented as a Functional Mock-up Unit (FMU), thus enables parameter estimation of models designed in modeling tools following the standardized interface, the Functional Mock-up Interface (FMI), such as Dymola.
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| 2. |
- Lagerholm, Sofia, et al.
(author)
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Genetic loci for bone architecture determined by three-dimensional CT in crosses with the diabetic GK rat.
- 2010
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In: Bone. - : Elsevier BV. - 1873-2763 .- 8756-3282. ; 47, s. 1039-1047
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Journal article (peer-reviewed)abstract
- The F344 rat carries alleles contributing to bone fragility while the GK rat spontaneously develops type-2 diabetes. These characteristics make F344xGK crosses well suited for the identification of genes related to bone size and allow for future investigation on the association with type-2 diabetes. The aim of this study was to identify quantitative trait loci (QTLs) for bone size phenotypes measured by a new application of three-dimensional computed tomography (3DCT) and to investigate the effects of sex- and reciprocal cross. Tibia from male and female GK and F344 rats, representing the parental, F1 and F2 generations, were examined with 3DCT and analyzed for: total and cortical volumetric BMD, straight and curved length, peri- and endosteal area at mid-shaft. F2 progeny (108 male and 98 female) were genotyped with 192 genome-wide microsatellite markers (average distance 10cM). Sex- and reciprocal cross-separated QTL analyses were performed for the identification of QTLs linked to 3DCT phenotypes and true interactions were confirmed by likelihood ratio analysis in all F2 animals. Several genome-wide significant QTLs were found in the sex- and reciprocal cross-separated progeny on chromosomes (chr) 1, 3, 4, 9, 10, 14, and 17. Overlapping QTLs for both males and females in the (GKxF344)F2 progeny were located on chr 1 (39-67cM). This region confirms previously reported pQCT QTLs and overlaps loci for fasting glucose. Sex separated linkage analysis confirmed a male specific QTL on chr 9 (67-82cM) for endosteal area at the fibula site. Analyses separating the F2 population both by sex and reciprocal cross identified cross specific QTLs on chr 14 (males) and chr 3 and 4 (females). Two loci, chr 4 and 6, are unique to 3DCT and separate from pQCT generated loci. The 3DCT method was highly reproducible and provided high precision measurements of bone size in the rat enabling identification of new sex- and cross-specific loci. The QTLs on chr 1 indicate potential genetic association between bone-related phenotypes and traits affecting type-2 diabetes. The results illustrate the complexity of the genetic architecture of bone size phenotypes and demonstrate the importance of complementary methods for bone analysis.
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| 3. |
- Lagerholm, Sofia, et al.
(author)
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Identification of Candidate Gene Regions in the Rat by Co-Localization of QTLs for Bone Density, Size, Structure and Strength.
- 2011
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:7
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Journal article (peer-reviewed)abstract
- Susceptibility to osteoporotic fracture is influenced by genetic factors that can be dissected by whole-genome linkage analysis in experimental animal crosses. The aim of this study was to characterize quantitative trait loci (QTLs) for biomechanical and two-dimensional dual-energy X-ray absorptiometry (DXA) phenotypes in reciprocal F2 crosses between diabetic GK and normo-glycemic F344 rat strains and to identify possible co-localization with previously reported QTLs for bone size and structure. The biomechanical measurements of rat tibia included ultimate force, stiffness and work to failure while DXA was used to characterize tibial area, bone mineral content (BMC) and areal bone mineral density (aBMD). F2 progeny (108 males, 98 females) were genotyped with 192 genome-wide markers followed by sex- and reciprocal cross-separated whole-genome QTL analyses. Significant QTLs were identified on chromosome 8 (tibial area; logarithm of odds (LOD) = 4.7 and BMC; LOD = 4.1) in males and on chromosome 1 (stiffness; LOD = 5.5) in females. No QTLs showed significant sex-specific interactions. In contrast, significant cross-specific interactions were identified on chromosome 2 (aBMD; LOD = 4.7) and chromosome 6 (BMC; LOD = 4.8) for males carrying F344mtDNA, and on chromosome 15 (ultimate force; LOD = 3.9) for males carrying GKmtDNA, confirming the effect of reciprocal cross on osteoporosis-related phenotypes. By combining identified QTLs for biomechanical-, size- and qualitative phenotypes (pQCT and 3D CT) from the same population, overlapping regions were detected on chromosomes 1, 3, 4, 6, 8 and 10. These are strong candidate regions in the search for genetic risk factors for osteoporosis.
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