| 1. |
- Connolly, Stuart J., et al.
(författare)
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The Long-Term Multicenter Observational Study of Dabigatran Treatment in Patients With Atrial Fibrillation (RELY-ABLE) Study
- 2013
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Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 128:3, s. 237-243
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Tidskriftsartikel (refereegranskat)abstract
- Background During follow-up of between 1 and 3 years in the Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY) trial, 2 doses of dabigatran etexilate were shown to be effective and safe for the prevention of stroke or systemic embolism in patients with atrial fibrillation. There is a need for longer-term follow-up of patients on dabigatran and for further data comparing the 2 dabigatran doses. Methods and Results Patients randomly assigned to dabigatran in RE-LY were eligible for the Long-term Multicenter Extension of Dabigatran Treatment in Patients with Atrial Fibrillation (RELY-ABLE) trial if they had not permanently discontinued study medication at the time of their final RE-LY study visit. Enrolled patients continued to receive the double-blind dabigatran dose received in RE-LY, for up to 28 months of follow up after RE-LY (median follow-up, 2.3 years). There were 5851 patients enrolled, representing 48% of patients originally randomly assigned to receive dabigatran in RE-LY and 86% of RELY-ABLE-eligible patients. Rates of stroke or systemic embolism were 1.46% and 1.60%/y on dabigatran 150 and 110 mg twice daily, respectively (hazard ratio, 0.91; 95% confidence interval, 0.69-1.20). Rates of major hemorrhage were 3.74% and 2.99%/y on dabigatran 150 and 110 mg (hazard ratio, 1.26; 95% confidence interval, 1.04-1.53). Rates of death were 3.02% and 3.10%/y (hazard ratio, 0.97; 95% confidence interval, 0.80-1.19). Rates of hemorrhagic stroke were 0.13% and 0.14%/y. Conclusions During 2.3 years of continued treatment with dabigatran after RE-LY, there was a higher rate of major bleeding with dabigatran 150 mg twice daily in comparison with 110 mg, and similar rates of stroke and death.
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| 2. |
- Heistermann, Christine, et al.
(författare)
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Influence of execution tolerances for friction connections in circular and polygonal towers for wind converters
- 2017
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Ingår i: Advanced steel construction. - : Hong Kong Institute of Steel Construction. - 1816-112X. ; 13:4, s. 343-360
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Tidskriftsartikel (refereegranskat)abstract
- Friction connections with long open slotted holes have been proven to be a competitive alternative to the conventional flange connections in steel tubular towers for wind energy converters. As full-scale tests are not available, results of Finite Element Analysis (FEA) of the real-scale tower geometry are used in this paper to investigate the influence of tower cross section shape, execution tolerance (gap between the shells) and length of the connection on the bending resistance. Buckling behaviour of the shell in the vicinity of the friction connection in circular and polygonal towers is compared. The friction connection is thoroughly examined and recommendations for execution tolerances are given. The influence of two types of the execution tolerances on the connection strength is considered: inward bended "fingers", leading to inclined gaps, and a parallel gap created by different tower diameters.
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| 3. |
- Jain, Neeraj, et al.
(författare)
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Targetable genetic alterations of TCF4 (E2-2) drive immunoglobulin expression in diffuse large B cell lymphoma
- 2019
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Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 11:497
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Tidskriftsartikel (refereegranskat)abstract
- The activated B cell (ABC-like) subtype of diffuse large B cell lymphoma (DLBCL) is characterized by chronic activation of signaling initiated by immunoglobulin m (IgM). By analyzing the DNA copy number profiles of 1000 DLBCL tumors, we identified gains of 18q21.2 as the most frequent genetic alteration in ABC-like DLBCL. Using integrative analysis of matched gene expression profiling data, we found that the TCF4 (E2-2) transcription factor gene was the target of these alterations. Overexpression of TCF4 in ABC-like DLBCL cell lines led to its occupancy on immunoglobulin (IGHM) and MYC gene enhancers and increased expression of these genes at the transcript and protein levels. Inhibition of TCF4 activity with dominant-negative constructs was synthetically lethal to ABC-like DLBCL cell lines harboring TCF4 DNA copy gains, highlighting these gains as an attractive potential therapeutic target. Furthermore, the TCF4 gene was one of the top BRD4-regulated genes in DLBCL cell lines. BET proteolysistargeting chimera (PROTAC) ARV771 extinguished TCF4, MYC, and IgM expression and killed ABC-like DLBCL cells in vitro. In DLBCL xenograft models, ARV771 treatment reduced tumor growth and prolonged survival. This work highlights a genetic mechanism for promoting immunoglobulin signaling in ABC-like DLBCL and provides a functional rationale for the use of BET inhibitors in this disease.
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| 4. |
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| 5. |
- Pavlovic, Marko, et al.
(författare)
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Connections in towers for wind converters : part I: Evaluation of down-scaled experiments
- 2015
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Ingår i: Journal of constructional steel research. - : Elsevier BV. - 0143-974X .- 1873-5983. ; 115, s. 445-457
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Tidskriftsartikel (refereegranskat)abstract
- The cost of a tubular steel tower supporting a wind converter becomes increasingly important in a competitive energy market. In-situ connection between tower segments is an important factor of the design. The tower segments are usually connected by welded ring flanges. An alternative solution based on a novel single lap friction connection is analysed. The purpose of the research presented in this paper is to thoroughly analyse the behaviour of both connections by an experimental testing programme and advanced finite element analysis (FEA). Down-scaled experiments of ring flange and friction connection in circular towers were performed using a 4-point bending test set-up. Altogether eight connections joining cylindrical shell, 1 m diameter, plate thickness 8 mm and total span of about 7 m were tested. A friction connection with long open slotted holes and two different cases of the ring flange connection are considered: with perfectly flat flanges and flanges with geometric imperfection. Results of advanced quasi-static FEA, using explicit dynamic solver and ductile damage material model for bolts, are compared to experiments. Failure modes, bolt forces and distribution of meridional membrane stresses in the shell in the vicinity of connections are analysed. Existing hand-calculation models, for the bolt force and normal stress distribution in the shell are validated by experiments and FEA.
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| 6. |
- Pavlovic, Marko, et al.
(författare)
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Connections in towers for wind converters : Part II: The friction connection behaviour
- 2015
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Ingår i: Journal of constructional steel research. - : Elsevier BV. - 0143-974X .- 1873-5983. ; 115, s. 458-466
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Tidskriftsartikel (refereegranskat)abstract
- A novel friction connection consisting of a single lap joint with long open slotted holes is proposed for use in tubular towers for wind converters for in-situ connections. This is a competitive alternative to the common ring flange connection as it has been shown in the European Project “HISTWIN”. Two sets of experiments are analysed: the down-scaled tubular steel tower 4-point bending experiments using high-strength bolts M20 and a single lap joint using plate thickness 25 mm and tension control bolts M30.The main motivation for this paper is a much higher bending resistance obtained in the 4-point bending experiments compared to predictions based on hand-calculation models.Results of experiments are used to validate finite element analysis (FEA). Explicit solver and the most realistic geometry of the bolts are the main characteristics of the FEA performed. Very good agreement between the experiments and FEA results is obtained, which provides credibility of the computational approach used to thoroughly examine experimental results. New evidences of the friction connection behaviour are provided: a short-term loss of preloading force due to external loading, transfer of shear force in the single lap joint and influence of the slotted hole on the joint resistance.Results obtained from hand-calculation models are used to predict the loss of preloading, the bending resistance of the connection and meridional stresses in the tower shell in the vicinity of the connection, which are compared to the experiments and the FEA. Recommendations related to use of the hand-calculation models in the design are provided.
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| 7. |
- Pavlović, Marko, et al.
(författare)
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Friction connection vs. ring flange connection in steel towers for wind converters
- 2015
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Ingår i: Engineering structures. - : Elsevier BV. - 0141-0296 .- 1873-7323. ; 98, s. 151-162
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Tidskriftsartikel (refereegranskat)abstract
- Tubular steel towers are the most commonly used structures to support wind converters. Towers are fabricated in welded segments, complying with the traffic requirements for transportation, and in-situ assembled. Ring flange connections are used to connect two segments. Fatigue endurance of the ring flange to the shell weld, class 71, is often the design criterion and imposes a limit on the shell thickness. Recently studied friction connections with long opened slotted holes, in HISTWIN and HISTWIN2 projects, provides a remedy for this limitation. The main purpose of this paper is to compare performance of the ring flange connection and the novel friction considering connection of a real tubular tower segment 3.37 m in diameter and 24 mm shell thickness. This cross-section is designed for the ultimate load MEd = 45.8 MNm and the steel grade S355. Finite Element Method is used to investigate possible failure modes of the connection. Advanced FEA comprise the realistic geometry of the connection, ductile damage material model and element removal using explicit dynamic solver. This allows sophisticated analysis of the behaviour and direct comparison of the results for both connection alternatives. The FEA is validated by down-scaled experiments performed previously within the HISTWIN project. The friction connection is thoroughly examined: geometry of the connection, influence of the shell imperfection in the vicinity of the connection and possible use of higher resistance steel grades. By focusing on key issues of the friction connection recommendations for the design are provided together with a numerical example.
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| 8. |
- Roselli, Carolina, et al.
(författare)
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Multi-ethnic genome-wide association study for atrial fibrillation
- 2018
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 50:9, s. 1225-1233
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Tidskriftsartikel (refereegranskat)abstract
- Atrial fibrillation (AF) affects more than 33 million individuals worldwide(1) and has a complex heritability(2). We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait locus analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF.
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| 9. |
- Veljkovic, Milan, et al.
(författare)
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High-strength tower in steel for wind turbines (Histwin) : Final report
- 2012
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Rapport (refereegranskat)abstract
- Innovative solutions for assembling joints of a tubular tower for wind turbines were studied and the project provides a background for design. This solution is simpler to produce and 80 % less expensive than traditional flange connection. Our feasibility study at the production plant indicates that the towers would be easy to assemble in situ. In addition to the direct cost savings due to the technical simplicity of the solution, the higher fatigue endurance than that of the flange connection is experimentally established. Further reduction of costs due to optimal use of higher-strength steel grades, especially in the bottom segments of the tower where the stiffening of the door opening is costly, is shown in the report. The total reduction of the costs for tower is estimated at about 10–15 % compared to the traditional tower. The project objectives are achieved in following sequences. • Experimental activities of the friction connection: small-scale tests to establish resistance of the friction connection for a variety of faying surfaces and bolt types, accompanying testing to ensure realistic input data for FEA, long-term testing to establish loss of pretension forces during the lifetime and fatigue tests.• Bending test of the friction and flange connection in a down-scaled tower. • Feasibility of production of the tower segments in the laboratory and at the production plant. • Monitoring of the existing tower to access a stress variation during the operation. • FEA analysis of experimental results and a complete case study of the monitored tower. Numerical examples for design of the friction connection are given for the sake of illustration and to encourage use of the new connection
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