| 1. |
- Nordmark, Gunnel, et al.
(författare)
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Association of EBF1, FAM167A(C8orf13)-BLK and TNFSF4 gene variants with primary Sjögren's syndrome
- 2011
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Ingår i: Genes and Immunity. - : Springer Science and Business Media LLC. - 1466-4879 .- 1476-5470. ; 12:2, s. 100-109
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Tidskriftsartikel (refereegranskat)abstract
- We performed a candidate gene association study in 540 patients with primary Sjögren's Syndrome (SS) from Sweden (n=344) and Norway (n=196) and 532 controls (n=319 Swedish, n=213 Norwegian). A total of 1139 single-nucleotide polymorphisms (SNPs) in 84 genes were analyzed. In the meta-analysis of the Swedish and Norwegian cohorts, we found high signals for association between primary SS and SNPs in three gene loci, not previously associated with primary SS. These are the early B-cell factor 1 (EBF1) gene, P=9.9 × 10−5, OR 1.68, the family with sequence similarity 167 member A–B-lymphoid tyrosine kinase (FAM167A–BLK) locus, P=4.7 × 10−4, OR 1.37 and the tumor necrosis factor superfamily (TNFSF4=Ox40L) gene, P=7.4 × 10−4, OR 1.34. We also confirmed the association between primary SS and the IRF5/TNPO3 locus and the STAT4 gene. We found no association between the SNPs in these five genes and the presence of anti-SSA/anti-SSB antibodies. EBF1, BLK and TNFSF4 are all involved in B-cell differentiation and activation, and we conclude that polymorphisms in several susceptibility genes in the immune system contribute to the pathogenesis of primary SS.
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| 4. |
- Gao, Kun, et al.
(författare)
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Microstructure-based numerical modeling of the solid-fluid coupling interaction in acoustic foams
- 2013
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Ingår i: Poromechanics V - Proceedings of the 5th Biot Conference on Poromechanics. - Reston, VA : American Society of Civil Engineers. ; , s. 2123-2130
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Konferensbidrag (refereegranskat)abstract
- In this paper, based on a representative volume element (RVE) and Slattery’s averaging theorem, parameters of Biot’s poroelastic equations for homogenous isotropic porous materials are obtained. According to Slattery’s averaging theorem, the coupling terms, which describe the inertial effects and the viscous effects, are represented by an integral of the solid-fluid interaction force. This relation provides a new approach to obtain the parameters required in Biot’s equations through a direct numerical simulation of the RVE. An example of a 2D RVE is given and simulations of sound propagation in an impedance tube with a foam are conducted using Biot’s equations. It is shown that the numerical coupling mass obtained from this new approach behaves qualitatively the same as an associated phenomenological model.
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| 5. |
- Gao, Kun, et al.
(författare)
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Microstructure-based numerical modelling of foams for acoustic shielding
- 2014
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Ingår i: 21st International Congress on Sound and Vibration 2014, ICSV 2014. - : International Institute of Acoustics and Vibrations. - 9781634392389 ; , s. 881-887
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Konferensbidrag (refereegranskat)abstract
- In this paper, a numerical homogenization approach is proposed to obtain isotropic Biot's parameters based on the microstructure of an porous material. It is assumed that a macroscopic point can be represented by a microscopic Representative Volume Element (RVE) consisting of the solid and the fluid. The macroscopic properties are controlled by Biot's equations and the RVE is governed by linearized balance equations for momentum and linear constitutive laws. With suitable boundary conditions, the micro-macro relation is formulated based on consistency of energy. Then, Biot's parameters are calculated through the response of the RVE. By following this new homogenization approach, examples with simple microstructures are given and simulations of two sound absorption experiments are conducted by using Biot's equations. The results are compared with Direct Numerical Simulations and it shows a favourable performance of this new approach compared to the alternative Transfer Matrix Method.
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| 6. |
- Gustafsson, Mats G., et al.
(författare)
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Improving Bayesian credibility intervals for classifier error rates using maximum entropy empirical priors
- 2010
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Ingår i: Artificial Intelligence in Medicine. - : Elsevier BV. - 0933-3657 .- 1873-2860. ; 49:2, s. 93-104
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Tidskriftsartikel (refereegranskat)abstract
- Objective:Successful use of classifiers that learn to make decisions from a set of patient examples require robust methods for performance estimation. Recently many promising approaches for determination of an upper bound for the error rate of a single classifier have been reported but the Bayesian credibility interval (Cl) obtained from a conventional holdout test still delivers one of the tightest bounds. The conventional Bayesian CI becomes unacceptably large in real world applications where the test set sizes are less than a few hundred. The source of this problem is that fact that the Cl is determined exclusively by the result on the test examples. In other words, there is no information at all provided by the uniform prior density distribution employed which reflects complete lack of prior knowledge about the unknown error rate. Therefore, the aim of the study reported here was to study a maximum entropy (ME) based approach to improved prior knowledge and Bayesian CIs, demonstrating its relevance for biomedical research and clinical practice.Method and material:It is demonstrated how a refined non-uniform prior density distribution can be obtained by means of the ME principle using empirical results from a few designs and tests using non-overlapping sets of examples.Results:Experimental results show that ME based priors improve the CIs when employed to four quite different simulated and two real world data sets.Conclusions:An empirically derived ME prior seems promising for improving the Bayesian Cl for the unknown error rate of a designed classifier.
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| 9. |
- Koehbach, Johannes, et al.
(författare)
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Oxytocic plant cyclotides as templates for peptide G protein-coupled receptor ligand design
- 2013
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 110:52, s. 21183-21188
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Tidskriftsartikel (refereegranskat)abstract
- Cyclotides are plant peptides comprising a circular backbone and three conserved disulfide bonds that confer them with exceptional stability. They were originally discovered in Oldenlandia affinis based on their use in traditional African medicine to accelerate labor. Recently, cyclotides have been identified in numerous plant species of the coffee, violet, cucurbit, pea, potato, and grass families. Their unique structural topology, high stability, and tolerance to sequence variation make them promising templates for the development of peptide-based pharmaceuticals. However, the mechanisms underlying their biological activities remain largely unknown; specifically, a receptor for a native cyclotide has not been reported hitherto. Using bioactivity-guided fractionation of an herbal peptide extract known to indigenous healers as "kalata-kalata," the cyclotide kalata B7 was found to induce strong contractility on human uterine smooth muscle cells. Radioligand displacement and second messenger-based reporter assays confirmed the oxytocin and vasopressin V-1a receptors, members of the G protein-coupled receptor family, as molecular targets for this cyclotide. Furthermore, we show that cyclotides can serve as templates for the design of selective G protein-coupled receptor ligands by generating an oxytocin-like peptide with nanomolar affinity. This nonapeptide elicited dose-dependent contractions on human myometrium. These observations provide a proof of concept for the development of cyclotide-based peptide ligands.
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| 10. |
- Nordlund, Jessica, et al.
(författare)
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Digital gene expression profiling of primary acute lymphoblastic leukemia cells
- 2012
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Ingår i: Leukemia. - : Nature Publishing Group. - 0887-6924 .- 1476-5551. ; 26:6, s. 1218-1227
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Tidskriftsartikel (refereegranskat)abstract
- We determined the genome-wide digital gene expression (DGE) profiles of primary acute lymphoblastic leukemia (ALL) cells from 21 patients taking advantage of `second-generation sequencing technology. Patients included in this study represent four cytogenetically distinct subtypes of B-cell precursor (BCP) ALL and T-cell lineage ALL (T-ALL). The robustness of DGE combined with supervised classification by nearest shrunken centroids (NSC) was validated experimentally and by comparison with published expression data for large sets of ALL samples. Genes that were differentially expressed between BCP ALL subtypes were enriched to distinct signaling pathways with dic(9;20) enriched to TP53 signaling, t(9;22) to interferon signaling, as well as high hyperdiploidy and t(12;21) to apoptosis signaling. We also observed antisense tags expressed from the non-coding strand of similar to 50% of annotated genes, many of which were expressed in a subtype-specific pattern. Antisense tags from 17 gene regions unambiguously discriminated between the BCP ALL and T-ALL subtypes, and antisense tags from 76 gene regions discriminated between the 4 BCP subtypes. We observed a significant overlap of gene regions with alternative polyadenylation and antisense transcription (Pless than1 x 10(-15)). Our study using DGE profiling provided new insights into the RNA expression patterns in ALL cells.
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