| 1. |
- Sharapov, S.E., et al.
(author)
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Energetic particle instabilities in fusion plasmas
- 2013
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In: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 53:10, s. 104022-
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Journal article (peer-reviewed)abstract
- Remarkable progress has been made in diagnosing energetic particle instabilities on present-day machines and in establishing a theoretical framework for describing them. This overview describes the much improved diagnostics of Alfvén instabilities and modelling tools developed world-wide, and discusses progress in interpreting the observed phenomena. A multi-machine comparison is presented giving information on the performance of both diagnostics and modelling tools for different plasma conditions outlining expectations for ITER based on our present knowledge.
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| 2. |
- Giampietro, C, et al.
(author)
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The alternative splicing factor Nova2 regulates vascular development and lumen formation
- 2015
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6, s. 8479-
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Journal article (peer-reviewed)abstract
- Vascular lumen formation is a fundamental step during angiogenesis; yet, the molecular mechanisms underlying this process are poorly understood. Recent studies have shown that neural and vascular systems share common anatomical, functional and molecular similarities. Here we show that the organization of endothelial lumen is controlled at the post-transcriptional level by the alternative splicing (AS) regulator Nova2, which was previously considered to be neural cell-specific. Nova2 is expressed during angiogenesis and its depletion disrupts vascular lumen formation in vivo. Similarly, Nova2 depletion in cultured endothelial cells (ECs) impairs the apical distribution and the downstream signalling of the Par polarity complex, resulting in altered EC polarity, a process required for vascular lumen formation. These defects are linked to AS changes of Nova2 target exons affecting the Par complex and its regulators. Collectively, our results reveal that Nova2 functions as an AS regulator in angiogenesis and is a novel member of the ‘angioneurins’ family.
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| 3. |
- Harbicht, Andrew, et al.
(author)
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Guiding migrating salmonid smolts : Experimentally assessing the performance of angled and inclined screens with varying gap widths
- 2022
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In: Ecological Engineering. - : Elsevier. - 0925-8574 .- 1872-6992. ; 174, s. 1-8
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Journal article (peer-reviewed)abstract
- The loss of longitudinal connectivity in regulated rivers, both up- and downstream, has been detrimental for biodiversity worldwide. While progress has been made regarding upstream fish passage solutions, many questions remain unanswered regarding downstream passage alternatives. To address these knowledge gaps, we used Atlantic salmon (S. salar) smolts to experimentally assess the guidance efficiency and passage rates produced by several common screen-and-bypass fish guidance systems. Vertical screens with horizontally oriented bars extending across a turbine intake channel at a shallow angle (angled guidance screens), combined with a single, full-depth bypass entrance at their downstream end, were on average 20% more effective and produced passage rates that were 10 times higher than screens which extended perpendicularly across a turbine intake channel with vertically oriented bars that rose gradually towards the surface (inclined guidance screens) and with a bypass at the surface, on either side of the screen. Among inclined screens, gap width was negatively associated with guidance efficiencies and the smallest gap width (15 mm) exhibited a 41% greater guidance efficiency than the largest (30 mm). Among angled screens, performance was more closely linked to construction material as metal racks produced passage rates over three times faster than flexible Kevlar netting. Overall, passage through the guidance screens, and therefore into a tentative turbine intake area, was positively associated with gap width and was twice as prevalent among the inclined relative to angled guidance screens. Ultimately, an angled guidance screen with a 30 mm gap width produced the highest guidance efficiency and passage rates (a 30% improvement over the next best screen), while an inclined screen with a 30 mm gap width produced the lowest guidance efficiencies and passage rates. These results have implications for the suitability and performance of downstream fish passage solutions at both large- and small-scale hydropower plants where passage solutions are currently lacking or inadequate.
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| 6. |
- Angiolini, Francesca, et al.
(author)
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A novel L1CAM isoform with angiogenic activity generated by NOVA2-mediated alternative splicing
- 2019
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In: eLIFE. - 2050-084X. ; 8
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Journal article (peer-reviewed)abstract
- The biological players involved in angiogenesis are only partially defined. Here, we report that endothelial cells (ECs) express a novel isoform of the cell-surface adhesion molecule L1CAM, termed L1-ΔTM. The splicing factor NOVA2, which binds directly to L1CAM pre-mRNA, is necessary and sufficient for the skipping of L1CAM transmembrane domain in ECs, leading to the release of soluble L1-ΔTM. The latter exerts high angiogenic function through both autocrine and paracrine activities. Mechanistically, L1-ΔTM-induced angiogenesis requires fibroblast growth factor receptor-1 signaling, implying a crosstalk between the two molecules. NOVA2 and L1-ΔTM are overexpressed in the vasculature of ovarian cancer, where L1-ΔTM levels correlate with tumor vascularization, supporting the involvement of NOVA2-mediated L1-ΔTM production in tumor angiogenesis. Finally, high NOVA2 expression is associated with poor outcome in ovarian cancer patients. Our results point to L1-ΔTM as a novel, EC-derived angiogenic factor which may represent a target for innovative antiangiogenic therapies.
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| 7. |
- Bodin, Helena, 1964-, et al.
(author)
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Afterword. World literature in the making
- 2022
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In: Literature and the Making of the World. - London : Bloomsbury Academic. - 9781501374159 - 9781501374173 - 9781501374166 - 9781501374180 ; , s. 307-311
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Book chapter (peer-reviewed)
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| 8. |
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| 9. |
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| 10. |
- Jensen, Lasse, et al.
(author)
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Disruption of the Extracellular Matrix Progressively Impairs Central Nervous System Vascular Maturation Downstream of beta-Catenin Signaling
- 2019
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In: Arteriosclerosis, Thrombosis and Vascular Biology. - : LIPPINCOTT WILLIAMS & WILKINS. - 1079-5642 .- 1524-4636. ; 39:7, s. 1432-1447
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Journal article (peer-reviewed)abstract
- Objective- The Wnt/beta-catenin pathway orchestrates development of the blood-brain barrier, but the downstream mechanisms involved at different developmental windows and in different central nervous system (CNS) tissues have remained elusive. Approach and Results- Here, we create a new mouse model allowing spatiotemporal investigations of Wnt/beta-catenin signaling by induced overexpression of Axin1, an inhibitor of beta-catenin signaling, specifically in endothelial cells (Axin1(iEC)-(OE)). AOE (Axin1 overexpression) in Axin1(iEC)-(OE) mice at stages following the initial vascular invasion of the CNS did not impair angiogenesis but led to premature vascular regression followed by progressive dilation and inhibition of vascular maturation resulting in forebrain-specific hemorrhage 4 days post-AOE. Analysis of the temporal Wnt/beta-catenin driven CNS vascular development in zebrafish also suggested that Axin1(iEC)-(OE) led to CNS vascular regression and impaired maturation but not inhibition of ongoing angiogenesis within the CNS. Transcriptomic profiling of isolated, beta-catenin signaling-deficient endothelial cells during early blood-brain barrier-development (E11.5) revealed ECM (extracellular matrix) proteins as one of the most severely deregulated clusters. Among the 20 genes constituting the forebrain endothelial cell-specific response signature, 8 (Adamtsl2, Apod, Ctsw, Htra3, Pglyrp1, Spock2, Ttyh2, and Wfdc1) encoded bona fide ECM proteins. This specific beta-catenin-responsive ECM signature was also repressed in Axin1(iEC)-(OE) and endothelial cell-specific beta-catenin-knockout mice (Ctnnb1-KOiEC) during initial blood-brain barrier maturation (E14.5), consistent with an important role of Wnt/beta-catenin signaling in orchestrating the development of the forebrain vascular ECM. Conclusions- These results suggest a novel mechanism of establishing a CNS endothelium-specific ECM signature downstream of Wnt-beta-catenin that impact spatiotemporally on blood-brain barrier differentiation during forebrain vessel development.
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| 12. |
- Ning, FCF, et al.
(author)
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VEGF-B ablation in pancreatic β-cells upregulates insulin expression without affecting glucose homeostasis or islet lipid uptake
- 2020
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In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1, s. 923-
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Journal article (peer-reviewed)abstract
- Type 2 diabetes mellitus (T2DM) affects millions of people and is linked with obesity and lipid accumulation in peripheral tissues. Increased lipid handling and lipotoxicity in insulin producing β-cells may contribute to β-cell dysfunction in T2DM. The vascular endothelial growth factor (VEGF)-B regulates uptake and transcytosis of long-chain fatty acids over the endothelium to tissues such as heart and skeletal muscle. Systemic inhibition of VEGF-B signaling prevents tissue lipid accumulation, improves insulin sensitivity and glucose tolerance, as well as reduces pancreatic islet triglyceride content, under T2DM conditions. To date, the role of local VEGF-B signaling in pancreatic islet physiology and in the regulation of fatty acid trans-endothelial transport in pancreatic islet is unknown. To address these questions, we have generated a mouse strain where VEGF-B is selectively depleted in β-cells, and assessed glucose homeostasis, β-cell function and islet lipid content under both normal and high-fat diet feeding conditions. We found that Vegfb was ubiquitously expressed throughout the pancreas, and that β-cell Vegfb deletion resulted in increased insulin gene expression. However, glucose homeostasis and islet lipid uptake remained unaffected by β-cell VEGF-B deficiency.
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| 13. |
- Nyqvist, D, et al.
(author)
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Donor islet endothelial cells participate in formation of functional vessels within pancreatic islet grafts
- 2005
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In: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 54:8, s. 2287-2293
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Journal article (peer-reviewed)abstract
- Pancreatic islet transplantation has emerged as a therapy for type 1 diabetes and is today performed using both freshly isolated and cultured islets. Islet blood vessels are disrupted during islet isolation; therefore, proper revascularization of the transplanted islets is of great importance for islet graft function and survival. We have studied intraislet endothelial cells after islet isolation, during islet culture, and following islet transplantation. By isolating islets from the transgenic Tie2-GFP (green fluorescent protein) mouse, characterized by an endothelial cell–specific expression of GFP, living endothelial cells could be studied in intact islets utilizing two-photon laser-scanning microscopy (TPLSM). Intraislet endothelial cells were found to survive islet transplantation but to rapidly disappear during islet culture. By transplanting freshly isolated Tie2-GFP islets and applying a novel ex vivo model for simultaneous perfusion and TPLSM imaging of the graft-bearing kidneys, GFP fluorescent endothelial cells were found to extensively contribute to vessels within the islet graft vasculature. Real-time imaging of the flow through the islet graft vasculature confirmed that the donor-derived vessels were functionally integrated. Hence, intraislet endothelial cells have the capability of participating in revascularization of pancreatic islets subsequent to transplantation. Therefore, preservation of intraislet endothelial cell mass may improve long-term graft function.
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| 14. |
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| 15. |
- Nyqvist, Daniel, et al.
(author)
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Downstream migration and multiple dam passage by Atlantic salmon smolts
- 2017
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In: North American Journal of Fisheries Management. - : Taylor & Francis. - 0275-5947 .- 1548-8675. ; 4:37, s. 816-828
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Journal article (peer-reviewed)abstract
- The purpose of this study was to investigate behavior and survival of radio-tagged wild and hatchery-reared landlocked Atlantic Salmon Salmo salar smolts as they migrated past three hydropower dams equipped with fish bypass solutions in the Winooski River, Vermont. Among hatchery-reared smolts, those released early were more likely to initiate migration and did so after less delay than those released late. Once migration was initiated, however, the late-released hatchery smolts migrated at greater speeds. Throughout the river system, hatchery-reared fish performed similarly to wild fish. Dam passage rates varied between the three dams and was highest at the dam where unusually high spill levels occurred throughout the study period. Of the 50 fish that did migrate downstream, only 10% managed to reach the lake. Migration success was low despite the presence of bypass solutions, underscoring the need for evaluations of remedial measures; simply constructing a fishway is not synonymous with providing fish passage.
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| 19. |
- Valachis, A., 1984-, et al.
(author)
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Palbociclib dose patterns in Swedish patients with metastatic breast cancer : 5-year update from the SIRI study
- 2023
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In: Annals of Oncology. - : Elsevier. - 0923-7534 .- 1569-8041. ; 34:Suppl. 2, s. S362-S362
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Journal article (other academic/artistic)abstract
- Background: Although palbociclib combined with endocrine therapy is a well-established treatment option in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC), there is limited evidence on patterns of dose reductions in real-world setting. The Swedish Ibrance Registries Insights (SIRI) study investigated real-world dose patterns using a nationwide cohort of palbociclib-treated MBC patients...Methods: This was a retrospective study utilizing population-based Swedish Health Data Registers. The cohort included all patients ≥ 18 years with ≥ 1 dispensation of palbociclib from January 2017 – June 2022. Minimum follow-up was 3 months. Starting dose and dose changes for the full population and for different age groups, in total and over time, was investigated...Results: 2058 patients were identified and the median (IQR) age at treatment initiation was 68.4 (15.7) years. Patients were stratified into three age groups: <50, 50-69, ≥70 years, with the following distribution: 9.9%, 46.1%, and 44.0%, respectively. Most patients were initiated on 125 mg (82.0%), with a lower share for older patients (≥70 years; 74.4%). In total, 45.5% of patients had ≥ 1 dose reduction, with a higher frequency for older patients (≥70 years; 48.5%). Median (IQR) time to first dose...Conclusions: Most Swedish palbociclib-treated patients were initiated on the recommended dose, but a lower starting dose and a higher frequency of dose reductions were observed for older patients. The time to dose reduction was equal across age groups, whereas the probability for dose reduction increased over time for older patients, and for patients with a start dose of 100 mg...
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