| 1. |
- Benson, Mikael, 1954, et al.
(författare)
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A network-based analysis of the late-phase reaction of the skin.
- 2006
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Ingår i: The Journal of allergy and clinical immunology. - : Elsevier BV. - 0091-6749 .- 1097-6825. ; 118:1, s. 220-5
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The late-phase reaction (LPR) of the skin is an in vivo model of allergic inflammation. OBJECTIVE: We sought to identify disease-associated pathways in the LPR using a network-based analysis. METHODS: The LPR was examined by means of DNA microarray analysis of skin biopsy specimens from 10 patients with allergic rhinitis and 10 healthy control subjects. The results were further analyzed in 2 different materials consisting of nasal fluids and allergen-challenged CD4(+) T cells from patients with allergic rhinitis. RESULTS: The DNA microarray analysis revealed several genes of known relevance to allergy. The eosinophil marker Charcot-Leyden crystal protein (CLC) that encodes Charcot-Leyden crystal protein differed most in expression. A network-based analysis showed upregulation of IL-4- and CCL4-dependent pathways and downregulation of a TGF-beta-induced pathway. CCL4 is expressed by CD4(+) T cells and chemotactic for eosinophils. We hypothesized that allergen induces release of CCL4 from T(H)2 cells and that this contributes to influx of eosinophils. Further analysis showed increase of CCL4 protein in nasal fluids from allergic patients during the season. Allergen challenge of PBMCs resulted in proliferation of T(H)2 cells and increased production of CCL4 in CD4(+) T cells from allergic patients. An analysis of the DNA microarray data revealed a significant correlation between CCL4 and the eosinophil marker CLC. CONCLUSION: A network-based analysis of the LPR showed increased activity of IL-4- and CCL4- dependent pathways and downregulation of the TGF-beta-induced pathway. Allergen-induced release of CCL4 from T(H)2 cells might contribute to influx of eosinophils during the LPR. CLINICAL IMPLICATIONS: Involvement of multiple interacting pathways indicates that it might be difficult to identify one single mediator as a biomarker or drug target in allergic inflammation.
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| 2. |
- Andersson, A., et al.
(författare)
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FLT3 mutations in a 10 year consecutive series of 177 childhood acute leukemias and their impact on global gene expression patterns
- 2008
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Ingår i: Genes, Chromosomes and Cancer. - : Wiley. - 1045-2257 .- 1098-2264. ; 47:1, s. 64-70
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Tidskriftsartikel (refereegranskat)abstract
- During 1995-2004, 209 children/adolescents were diagnosed with acute lymphoblastic or myeloid leukemia (ALL, AML) in Southern Sweden, of which 177 (85%), comprising 128 B-lineage ALL, 34 AML, and 15 T-cell ALL, could be analyzed for internal tandem duplications (ITD) and activating point mutations in the second tyrosine kinase domain (ATKD) of FLT3. Seventeen (10%) FLT3 mutations (6 ITD, 11 ATKD, mutually exclusive) were detected. None of the T-cell ALL harbored any mutations. ITD and ATKD were found in 2% and 6% of the B-lineage ALL and in 12% and 9% of the AML, being particularly common in high hyperdiploid ALL (14%), ALL (20%), and AML (23%) with 11q23/MLL rearrangements, and in AML with a normal karyotype (60%). All ATKD-positive AML with MLL rearrangements harbored the t(9,11)(p21,q23). Global gene expression data were available for 76 of the B-lineage ALL and 19 of the AML, of which 6 (8%) and 3 (16%) had FLT3 mutations, respectively. No distinct expression pattern associated with FLT3 mutations was identified. © 2007 Wiley-Liss, Inc.
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| 4. |
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| 5. |
- Bruhn, Sören, et al.
(författare)
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Increased expression of IRF4 and ETS1 in CD4+ cells from patients with intermittent allergic rhinitis
- 2012
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Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : John Wiley and Sons. - 0105-4538 .- 1398-9995. ; 67:1, s. 33-40
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Tidskriftsartikel (refereegranskat)abstract
- Background: The transcription factor (TF) IRF4 is involved in the regulation of Th1, Th2, Th9, and Th17 cells, and animal studies have indicated an important role in allergy. However, IRF4 and its target genes have not been examined in human allergy. Methods: IRF4 and its target genes were examined in allergen-challenged CD4+ cells from patients with IAR, using combined gene expression microarrays and chromatin immunoprecipitation chips (ChIP-chips), computational target prediction, and RNAi knockdowns. Results: IRF4 increased in allergen-challenged CD4+ cells from patients with IAR, and functional studies supported its role in Th2 cell activation. IRF4 ChIP-chip showed that IRF4 regulated a large number of genes relevant to Th cell differentiation. However, neither Th1 nor Th2 cytokines were the direct targets of IRF4. To examine whether IRF4 induced Th2 cytokines via one or more downstream TFs, we combined gene expression microarrays, ChIP-chips, and computational target prediction and found a putative intermediary TF, namely ETS1 in allergen-challenged CD4+ cells from allergic patients. ETS1 increased significantly in allergen-challenged CD4+ cells from patients compared to controls. Gene expression microarrays before and after ETS1 RNAi knockdown showed that ETS1 induced Th2 cytokines as well as disease-related pathways. Conclusions: Increased expression of IRF4 in allergen-challenged CD4+ cells from patients with intermittent allergic rhinitis leads to activation of a complex transcriptional program, including Th2 cytokines.
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| 6. |
- Bölke, Kristofer, et al.
(författare)
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Experimental Determinations of Mixing Times in the IronArc Pilot Plant Process
- 2019
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Ingår i: Metals. - : MDPI. - 2075-4701. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- IronArc is a newly developed technology and an emerging future process for pig iron production. The long-term goal with this technology is to reduce the CO2 emissions and energy consumption compared to existing technologies. The production rate of this process is dependent on the stirring, which was investigated in the pilot plant process by measuring the mixing time in the slag bath. Moreover, slag investigations were done both based on light optical microscope studies as well as by Thermo-Calc calculations in order to determine the phases of the slag during operation. This was done because the viscosity (which is another important parameter) is dependent on the liquid and solid fractions of the slag. The overall results show that it was possible to determine the mixing time by means of the addition of a tracer (MnO2 powder) to the slag. The mixing time for the trials showed that the slag was homogenized after seconds. For two of the trials, homogenization had already been reached in the second sample after tracer addition, which means <= 8 s. The phase analysis from the slag indicated that the slag is in a liquid state during the operation of the process.
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| 7. |
- Koffert, J. P., et al.
(författare)
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Metformin treatment significantly enhances intestinal glucose uptake in patients with type 2 diabetes: Results from a randomized clinical trial
- 2017
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Ingår i: Diabetes Research and Clinical Practice. - : Elsevier BV. - 0168-8227 .- 1872-8227. ; 131, s. 208-216
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Tidskriftsartikel (refereegranskat)abstract
- Aims Metformin therapy is associated with diffuse intestinal 18F-fluoro-deoxyglucose (FDG) accumulation in clinical diagnostics using routine FDG-PET imaging. We aimed to study whether metformin induced glucose uptake in intestine is associated with the improved glycaemic control in patients with type 2 diabetes. Therefore, we compared the effects of metformin and rosiglitazone on intestinal glucose metabolism in patients with type 2 diabetes in a randomized placebo controlled clinical trial, and further, to understand the underlying mechanism, evaluated the effect of metformin in rats. Methods Forty-one patients with newly diagnosed type 2 diabetes were randomized to metformin (1g, b.i.d), rosiglitazone (4mg, b.i.d), or placebo in a 26-week double-blind trial. Tissue specific intestinal glucose uptake was measured before and after the treatment period using FDG-PET during euglycemic hyperinsulinemia. In addition, rats were treated with metformin or vehicle for 12weeks, and intestinal FDG uptake was measured in vivo and with autoradiography. Results Glucose uptake increased 2-fold in the small intestine and 3-fold in the colon for the metformin group and associated with improved glycemic control. Rosiglitazone increased only slightly intestinal glucose uptake. In rodents, metformin treatment enhanced intestinal FDG retention (P=0.002), which was localized in the mucosal enterocytes of the small intestine. Conclusions Metformin treatment significantly enhances intestinal glucose uptake from the circulation of patients with type 2 diabetes. This intestine-specific effect is associated with improved glycemic control and localized to mucosal layer. These human findings demonstrate directs effect of metformin on intestinal metabolism and elucidate the actions of metformin. Clinical trial number NCT02526615 © 2017 The Authors
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| 8. |
- Liu, Yu, et al.
(författare)
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Decarburization in an Electric Arc Furnace using Coupled Fluid dynamics and Thermodynamics
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- A coupled method of Fluid dynamics and Thermodynamics, named as Multi-zone Reaction Model, was established to simulate the flow pattern with bottom oxygen injection in a 145t electric arc furnace. The simulated maximum hot spot temperature and decarburization rate in the refining phase were compared against the data measured in the industrial operation. Moreover, the physical modeling was carried out to study the effect of nozzle size on the flow characteristics in the reaction zone. The results show, under high flow rates, the effect of nozzle size on the flow field in the reaction zone of the plume area can be neglected. The decarburization rate and hot spot temperature predicted by the modeling are consistent with the industrial measurements. The maximum hot spot temperature gradually decreases during the refining phase. The oxygen flow rate has a significant influence on the decarburization rate, hot spot temperature and average steel temperature. In terms of combined injection of O2 and inert argon gas, for a certain O2 flow rate, the decarburization rate increases due to the efficient mass transfer of carbon in the molten steel. Furthermore, for the replacement of argon using CO2, it is demonstrated that as the ratio of CO2 mass fraction increases from 0% to 40%, the maximum hot spot temperature decrease with the value of 570K, and the increment rate of average steel temperature, and the decarburization rate in the molten steel decrease with the ratio of 68%, and 81%, respectively. The endothermic reaction of CO2 with the molten steel results in a temperature drop in the plume above the hot spot zone.
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| 9. |
- Mobini, Reza, 1965, et al.
(författare)
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A module-based analytical strategy to identify novel disease-associated genes shows an inhibitory role for interleukin 7 Receptor in allergic inflammation.
- 2009
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Ingår i: BMC systems biology. - : Springer Science and Business Media LLC. - 1752-0509. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The identification of novel genes by high-throughput studies of complex diseases is complicated by the large number of potential genes. However, since disease-associated genes tend to interact, one solution is to arrange them in modules based on co-expression data and known gene interactions. The hypothesis of this study was that such a module could be a) found and validated in allergic disease and b) used to find and validate one ore more novel disease-associated genes. RESULTS: To test these hypotheses integrated analysis of a large number of gene expression microarray experiments from different forms of allergy was performed. This led to the identification of an experimentally validated reference gene that was used to construct a module of co-expressed and interacting genes. This module was validated in an independent material, by replicating the expression changes in allergen-challenged CD4+ cells. Moreover, the changes were reversed following treatment with corticosteroids. The module contained several novel disease-associated genes, of which the one with the highest number of interactions with known disease genes, IL7R, was selected for further validation. The expression levels of IL7R in allergen challenged CD4+ cells decreased following challenge but increased after treatment. This suggested an inhibitory role, which was confirmed by functional studies. CONCLUSION: We propose that a module-based analytical strategy is generally applicable to find novel genes in complex diseases.
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| 10. |
- Mohan, N. Krishna, et al.
(författare)
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Optical configurations in TV holography for deformation and shape measurement
- 2000
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Ingår i: Lasers in engineering (Print). - 0898-1507 .- 1029-029X. ; 10:2, s. 147-159
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Tidskriftsartikel (refereegranskat)abstract
- In recent years, TV holography is extensively implemented for determination of deformation and surface shape of diffusely reflecting surfaces. Such investigations are of primary importance in many applications, because these physical parameters are related to the functionality, integrity and performance of the engineering objects. In this paper, a new approach for determination of deformation and surface shape using simple optical configurations is presented. Description of each configuration, theory of fringe formation and the measuring sensitivity are discussed. Experimental results using four frame phase shifting technique are illustrated.
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