| 1. |
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| 2. |
- Turcot, Valerie, et al.
(författare)
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Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity
- 2018
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:1, s. 26-41
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are similar to 10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed similar to 7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.
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| 3. |
- Marouli, Eirini, et al.
(författare)
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Rare and low-frequency coding variants alter human adult height
- 2017
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 542:7640, s. 186-190
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Tidskriftsartikel (refereegranskat)abstract
- Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.
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| 4. |
- Justice, Anne E., et al.
(författare)
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Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution
- 2019
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:3, s. 452-469
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Tidskriftsartikel (refereegranskat)abstract
- Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF >= 5%) and nine low-frequency or rare (MAF < 5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants.
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| 5. |
- Wessel, Jennifer, et al.
(författare)
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Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility
- 2015
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Fasting glucose and insulin are intermediate traits for type 2 diabetes. Here we explore the role of coding variation on these traits by analysis of variants on the HumanExome BeadChip in 60,564 non-diabetic individuals and in 16,491 T2D cases and 81,877 controls. We identify a novel association of a low-frequency nonsynonymous SNV in GLP1R (A316T; rs10305492; MAF = 1.4%) with lower FG (beta = -0.09 +/- 0.01 mmol l(-1), P = 3.4 x 10(-12)), T2D risk (OR[95% CI] = 0.86[0.76-0.96], P = 0.010), early insulin secretion (beta = -0.07 +/- 0.035 pmol(insulin) mmol(glucose)(-1), P = 0.048), but higher 2-h glucose (beta = 0.16 +/- 0.05 mmol l(-1), P = 4.3 x 10(-4)). We identify a gene-based association with FG at G6PC2 (p(SKAT) = 6.8 x 10(-6)) driven by four rare protein-coding SNVs (H177Y, Y207S, R283X and S324P). We identify rs651007 (MAF = 20%) in the first intron of ABO at the putative promoter of an antisense lncRNA, associating with higher FG (beta = 0.02 +/- 0.004 mmol l(-1), P = 1.3 x 10(-8)). Our approach identifies novel coding variant associations and extends the allelic spectrum of variation underlying diabetes-related quantitative traits and T2D susceptibility.
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| 6. |
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| 7. |
- Scott, Robert A., et al.
(författare)
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A genomic approach to therapeutic target validation identifies a glucose-lowering GLP1R variant protective for coronary heart disease
- 2016
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Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 8:341
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Tidskriftsartikel (refereegranskat)abstract
- Regulatory authorities have indicated that new drugs to treat type 2 diabetes (T2D) should not be associated with an unacceptable increase in cardiovascular risk. Human genetics may be able to guide development of antidiabetic therapies by predicting cardiovascular and other health endpoints. We therefore investigated the association of variants in six genes that encode drug targets for obesity or T2D with a range of metabolic traits in up to 11,806 individuals by targeted exome sequencing and follow-up in 39,979 individuals by targeted genotyping, with additional in silico follow-up in consortia. We used these data to first compare associations of variants in genes encoding drug targets with the effects of pharmacological manipulation of those targets in clinical trials. We then tested the association of those variants with disease outcomes, including coronary heart disease, to predict cardiovascular safety of these agents. A low-frequency missense variant (Ala316Thr; rs10305492) in the gene encoding glucagon-like peptide-1 receptor (GLP1R), the target of GLP1R agonists, was associated with lower fasting glucose and T2D risk, consistent with GLP1R agonist therapies. The minor allele was also associated with protection against heart disease, thus providing evidence that GLP1R agonists are not likely to be associated with an unacceptable increase in cardiovascular risk. Our results provide an encouraging signal that these agents may be associated with benefit, a question currently being addressed in randomized controlled trials. Genetic variants associated with metabolic traits and multiple disease outcomes can be used to validate therapeutic targets at an early stage in the drug development process.
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| 8. |
- Manning, Alisa, et al.
(författare)
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A Low-Frequency Inactivating AKT2 Variant Enriched in the Finnish Population Is Associated With Fasting Insulin Levels and Type 2 Diabetes Risk
- 2017
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Ingår i: Diabetes. - : AMER DIABETES ASSOC. - 0012-1797 .- 1939-327X. ; 66:7, s. 2019-2032
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Tidskriftsartikel (refereegranskat)abstract
- To identify novel coding association signals and facilitate characterization of mechanisms influencing glycemic traits and type 2 diabetes risk, we analyzed 109,215 variants derived from exome array genotyping together with an additional 390,225 variants from exome sequence in up to 39,339 normoglycemic individuals from five ancestry groups. We identified a novel association between the coding variant (p.Pro50Thr) in AKT2 and fasting plasma insulin (FI), a gene in which rare fully penetrant mutations are causal for monogenic glycemic disorders. The low-frequency allele is associated with a 12% increase in FI levels. This variant is present at 1.1% frequency in Finns but virtually absent in individuals from other ancestries. Carriers of the FI-increasing allele had increased 2-h insulin values, decreased insulin sensitivity, and increased risk of type 2 diabetes (odds ratio 1.05). In cellular studies, the AKT2-Thr50 protein exhibited a partial loss of function. We extend the allelic spectrum for coding variants in AKT2 associated with disorders of glucose homeostasis and demonstrate bidirectional effects of variants within the pleckstrin homology domain of AKT2.
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| 9. |
- Sodergren, Erica, et al.
(författare)
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The genome of the sea urchin Strongylocentrotus purpuratus.
- 2006
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 314:5801, s. 941-52
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Tidskriftsartikel (refereegranskat)abstract
- We report the sequence and analysis of the 814-megabase genome of the sea urchin Strongylocentrotus purpuratus, a model for developmental and systems biology. The sequencing strategy combined whole-genome shotgun and bacterial artificial chromosome (BAC) sequences. This use of BAC clones, aided by a pooling strategy, overcame difficulties associated with high heterozygosity of the genome. The genome encodes about 23,300 genes, including many previously thought to be vertebrate innovations or known only outside the deuterostomes. This echinoderm genome provides an evolutionary outgroup for the chordates and yields insights into the evolution of deuterostomes.
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| 10. |
- Mahajan, Anubha, et al.
(författare)
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Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes
- 2018
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:4, s. 559-571
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Tidskriftsartikel (refereegranskat)abstract
- We aggregated coding variant data for 81,412 type 2 diabetes cases and 370,832 controls of diverse ancestry, identifying 40 coding variant association signals (P < 2.2 × 10−7); of these, 16 map outside known risk-associated loci. We make two important observations. First, only five of these signals are driven by low-frequency variants: even for these, effect sizes are modest (odds ratio ≤1.29). Second, when we used large-scale genome-wide association data to fine-map the associated variants in their regional context, accounting for the global enrichment of complex trait associations in coding sequence, compelling evidence for coding variant causality was obtained for only 16 signals. At 13 others, the associated coding variants clearly represent ‘false leads’ with potential to generate erroneous mechanistic inference. Coding variant associations offer a direct route to biological insight for complex diseases and identification of validated therapeutic targets; however, appropriate mechanistic inference requires careful specification of their causal contribution to disease predisposition.
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| 11. |
- Hirai, T., et al.
(författare)
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Thermal load testing of erosion-monitoring beryllium marker tile for the ITER-Like Wall Project at JET
- 2008
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Ingår i: Fusion engineering and design. - : Elsevier BV. - 0920-3796 .- 1873-7196. ; 83:7-9, s. 1072-1076
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Tidskriftsartikel (refereegranskat)abstract
- ITER-Like Wall Project has been launched at JET in order to perform a fully integrated test of plasma-facing materials. During the next major shutdown a full metal wall will be installed: tungsten in the divertor and beryllium in the main chamber. Beryllium erosion is one of key issues to be addressed. Special marker tiles have been designed for this purpose. Test coupons of such markers have been manufactured and examined. The performance test under high power deposition was carried in the electron beam facility JUDITH. The results of material characterization before and after high heat flux loads are presented. The samples survived, without macroscopic damage, power loads of up to 4.5 MW/m(2) for 10s (surface temperature similar to 650 degrees C) and 50 cyclic loads at 3.5 MW/m(2) lasting 10s each (surface temperature similar to 600 degrees C).
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| 12. |
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| 13. |
- Gasior, P., et al.
(författare)
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Laser-induced removal of co-deposits from graphitic plasma-facing components : Characterization of irradiated surfaces and dust particles
- 2009
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Ingår i: Journal of Nuclear Materials. - : Elsevier BV. - 0022-3115 .- 1873-4820. ; 390-91, s. 585-588
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Tidskriftsartikel (refereegranskat)abstract
- Laser-induced fuel desorption and ablation of co-deposited layers on limiter plates from the TEXTOR tokamak have been studied. Gas phase composition was monitored in situ, whereas the ex situ studies have been focused on the examination of irradiated surfaces and broad analysis of dust generated by ablation of co-deposits. The size of the dust grains is in the range of few nanometers to hundreds of micrometers. These are fuel-rich dust particles, as determined by nuclear reaction analysis. The presence of deuterium in dust indicates that not all fuel species are transferred to the gas phase during irradiation. This also suggests that photonic removal of fuel and the ablation of co-deposit from plasma-facing components may lead to the redistribution of fuel-containing dust to surrounding areas.
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| 14. |
- Hirai, T., et al.
(författare)
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Characterization and heat flux testing of beryllium coatings on Inconel for JET ITER-like wall project
- 2007
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Ingår i: Physica Scripta. - 0031-8949 .- 1402-4896. ; T128, s. 166-170
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Tidskriftsartikel (refereegranskat)abstract
- In order to perform a fully integrated material test, JET has launched the ITER-like wall project with the aim of installing a full metal wall during the next major shutdown. The material foreseen for the main chamber wall is bulk Be at the limiters and Be coatings on inconel tiles elsewhere. R&D process comprises global characterization ( structure, purity etc) of the evaporated films and testing of their performance under heat loads. The major results are (i) the layers have survived energy loads of 20 MJ m(-2) which is significantly above the required level of 5 - 10 MJ m(-2), (ii) melting limit of beryllium coating would be at the energy level of 30 MJ m(-2), (iii) cyclic thermal load of 10 MJ m(-2) for up to 50 cycles have not induced any noticeable damage such as flaking or detachment.
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| 15. |
- Makitie, AA, et al.
(författare)
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Head and neck cancer management in the Nordic countries: an effort to harmonize treatment
- 2017
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Ingår i: European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery. - : Springer Science and Business Media LLC. - 1434-4726. ; 274:5, s. 2363-2365
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 16. |
- Rubel, Marek J., et al.
(författare)
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Thick co-deposits and dust in controlled fusion devices with carbon walls : Fuel inventory and growth rate of co-deposited layers
- 2003
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Ingår i: Physica Scripta. - 0031-8949 .- 1402-4896. ; T103, s. 20-24
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Tidskriftsartikel (refereegranskat)abstract
- Recent results regarding the formation of co-deposits, fuel accumulation and overall material transport at the TEXTOR tokamak are described. Two categories of brittle flaking co-deposits were identified: (i) smooth stratified layers of a thickness of up to 50 mum and a fuel content of up to 16 at.%. (ii) granular and columnar structures reaching 1 mm in thickness and containing around 0.5 at.% of fuel species. They were formed on the blades of the toroidal belt pump limiter (similar to 15000 s of plasma operation) and on the neutraliser plates of this limiter (similar to 90000 s), respectively. A comparison is made to the fuel inventory measured in other controlled fusion devices with carbon walls.
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| 17. |
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| 18. |
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| 19. |
- Hulme, Heather E., et al.
(författare)
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Mass spectrometry imaging identifies palmitoylcarnitine as an immunological mediator during Salmonella Typhimurium infection
- 2017
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Salmonella Typhimurium causes a self-limiting gastroenteritis that may lead to systemic disease. Bacteria invade the small intestine, crossing the intestinal epithelium from where they are transported to the mesenteric lymph nodes (MLNs) within migrating immune cells. MLNs are an important site at which the innate and adaptive immune responses converge but their architecture and function is severely disrupted during S. Typhimurium infection. To further understand host-pathogen interactions at this site, we used mass spectrometry imaging (MSI) to analyse MLN tissue from a murine model of S. Typhimurium infection. A molecule, identified as palmitoylcarnitine (PalC), was of particular interest due to its high abundance at loci of S. Typhimurium infection and MLN disruption. High levels of PalC localised to sites within the MLNs where B and T cells were absent and where the perimeter of CD169(+) sub capsular sinus macrophages was disrupted. MLN cells cultured ex vivo and treated with PalC had reduced CD4(+) CD25(+) T cells and an increased number of B220(+) CD19(+) B cells. The reduction in CD4(+) CD25(+) T cells was likely due to apoptosis driven by increased caspase-3/7 activity. These data indicate that PalC significantly alters the host response in the MLNs, acting as a decisive factor in infection outcome.
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| 20. |
- Klyushina, E. S., et al.
(författare)
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Signatures for Berezinskii-Kosterlitz-Thouless critical behavior in the planar antiferromagnet BaNi2V2O8
- 2021
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Ingår i: Physical Review B. - : American Physical Society (APS). - 2469-9950 .- 2469-9969. ; 104:6
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Tidskriftsartikel (refereegranskat)abstract
- We investigate the critical properties of the spin-1 honeycomb antiferromagnet BaNi2V2O8, both below and above the ordering temperature T-N using neutron diffraction and muon spin rotation measurements. Our results characterize BaNi2V2O8 as a two-dimensional (2D) antiferromagnet across the entire temperature range, displaying a series of crossovers from 2D XY to 2D XXZ and then to 2D Heisenberg behavior with increasing temperature. In particular, the extracted critical exponent of the order parameter reveals a narrow temperature regime close to T-N, in which the system behaves as a 2D XY antiferromagnet. Above T-N, evidence for Berezinskii-Kosterlitz-Thouless behavior driven by vortex excitations is obtained from the scaling of the correlation length. Our experimental results are in agreement with classical and quantum Monte Carlo simulations performed using microscopic magnetic model Hamiltonians for BaNi2V2O8.
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| 21. |
- Moldan, Filip, et al.
(författare)
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The long-term fate of deposited nitrogen in temperate forest soils.
- 2020
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Ingår i: Biogeochemistry. - : Springer Science and Business Media LLC. - 0168-2563 .- 1573-515X. ; 150, s. 1-15
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Tidskriftsartikel (refereegranskat)abstract
- Increased anthropogenic nitrogen (N) inputs can alter the N cycle and affect forest ecosystem functions. The impact of increased N deposition depends among others on the ultimate fate of N in plant and soil N pools. Short-term studies (3–18 months) have shown that the organic soil layer was the dominant sink for N. However, longer time scales are needed to investigate the long-term fate of N. Therefore, the soils of four experimental forest sites across Europe were re-sampled ~ 2 decades after labelling with 15N. The sites covered a wide range of ambient N deposition varying from 13 to 58 kg N ha−1 year−1. To investigate the effects of different N loads on 15N recovery, ambient N levels were experimentally increased or decreased. We hypothesized that: (1) the mineral soil would become the dominant 15N sink after 2 decades, (2) long-term increased N deposition would lead to lower 15N recovery levels in the soil and (3) variables related to C dynamics would have the largest impact on 15N recovery in the soil. The results show that large amounts of the added 15N remain in the soil after 2 decades and at 2 out of 4 sites the 15N recovery levels are higher in the mineral soil than in the organic soil. The results show no clear responses of the isotopic signature to the changes in N deposition. Several environmental drivers are identified as controlling factors for long-term 15N recovery. Most drivers that significantly contribute to 15N recovery are strongly related to the soil organic matter (SOM) content. These findings are consistent with the idea that much of the added 15N is immobilized in the SOM. In the organic soil layer, we identify C stock, thickness of the organic layer, N-status and mean annual temperature of the forest sites as most important controlling factors. In the mineral soil we identify C stock, C content, pH, moisture content, bulk density, temperature, precipitation and forest stand age as most important controlling factors. Overall, our results show that these temperate forests are capable of retaining long-term increased N inputs preferably when SOM availability is high and SOM turnover and N availability are low.
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| 22. |
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| 23. |
- Rubel, Marek J., et al.
(författare)
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Overview of comprehensive characterisation of erosion zones on plasma facing components
- 2006
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Ingår i: Fusion engineering and design. - : Elsevier BV. - 0920-3796 .- 1873-7196. ; 81:1-7, s. 211-219
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Tidskriftsartikel (refereegranskat)abstract
- Morphology of carbon plasma facing components retrieved from the TEXTOR tokamak after long operation periods and exposure to total particle doses exceeding 7 x 10(26) m(-2) was determined. Emphasis was on the composition and structure of the erosion zones. Tiles from two limiters-the main toroidal belt pump ALT-II and auxiliary inner bumper-were examined using high-resolution microscopy, surface profilometry, ion beam analysis techniques and energy dispersive X-ray spectroscopy. The essence of results regarding the net-erosion zones is following: (i) microstructure of surfaces is significantly smoother than on a non-exposed graphite, whereas carbon fibre composites show similar appearance prior to the exposure and after; (ii) deuterium retention is 2-5 x 10(21) m(-2); (iii) the presence of plasma impurity atoms (e.g. metals) is detected predominantly in small cavities acting as local shadowed areas on the surface. The results are discussed in terms of processes of material erosion/re-deposition and tokamak operation conditions influencing the morphology of wall components.
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| 24. |
- Simon, Marie-Christine, et al.
(författare)
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Distinct alterations of gut morphology and microbiota characterize accelerated diabetes onset in nonobese diabetic mice
- 2020
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Ingår i: Journal of Biological Chemistry. - 0021-9258. ; 295:4, s. 969-980
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Tidskriftsartikel (refereegranskat)abstract
- The rising prevalence of type 1 diabetes (T1D) over the past decades has been linked to lifestyle changes, but the underlying mechanisms are largely unknown. Recent findings point to gut-associated mechanisms in the control of T1D pathogenesis. In nonobese diabetic (NOD) mice, a model of T1D, diabetes development accelerates after deletion of the Toll-like receptor 4 (TLR4). We hypothesized that altered intestinal functions contribute to metabolic alterations, which favor accelerated diabetes development in TLR4-deficient (TLR4(?/?)) NOD mice. In 70?90-day-old normoglycemic (prediabetic) female NOD TLR4(+/+) and NOD TLR4(?/?) mice, gut morphology and microbiome composition were analyzed. Parameters of lipid metabolism, glucose homeostasis, and mitochondrial respiratory activity were measured in vivo and ex vivo. Compared with NOD TLR4(+/+) mice, NOD TLR4(?/?) animals showed lower muscle mass of the small intestine, higher abundance of Bacteroidetes, and lower Firmicutes in the large intestine, along with lower levels of circulating short-chain fatty acids (SCFA). These changes are associated with higher body weight, hyperlipidemia, and severe insulin and glucose intolerance, all occurring before the onset of diabetes. These mice also exhibited insulin resistance?related abnormalities of energy metabolism, such as lower total respiratory exchange rates and higher hepatic oxidative capacity. Distinct alterations of gut morphology and microbiota composition associated with reduction of circulating SCFA may contribute to metabolic disorders promoting the progression of insulin-deficient diabetes/T1D development.
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| 25. |
- Terzidis, Emmanouil, 1994, et al.
(författare)
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Tumor volume definitions in head and neck squamous cell carcinoma - Comparing PET/MRI and histopathology
- 2023
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Ingår i: Radiotherapy and Oncology. - : Elsevier BV. - 0167-8140. ; 180
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: In cancer treatment precise definition of the tumor volume is essential, but despite development in imaging modalities, this remains a challenge. Here, pathological tumor volumes from the surgical specimens were obtained and compared to tumor volumes defined from modern PET/ MRI hybrid imaging. The purpose is to evaluate mismatch between the volumes defined from imaging and pathology was estimated and potential clinical impact.Methods and Materials: Twenty-five patients with head and neck squamous cell carcinoma were scanned on an integrated PET/MRI system prior to surgery. Three gross tumor volumes (GTVs) from the primary tumor site were delineated defined from MRI (GTVMRI), PET (GTVPET) and one by utilizing both anatomical images and clinical information (GTVONCO). Twenty-five primary tumor specimens were extracted en bloc, scanned with PET/MRI and co-registered to the patient images. Each specimen was sectioned in blocks, sliced and stained with haematoxylin and eosin. All slices were digitalized and tumor delineated by a head and neck pathologist. The pathological tumor areas in all slices were interpolated yielding a pathological 3D tumor volume (GTVPATO). GTVPATO was compared with the imaging GTV's and potential mismatch was estimated.Results: Thirteen patients were included. The mean volume of GTVONCO was larger than the GTV's defined from PET or MRI. The mean mismatch of the GTVPATO compared to the GTVPET, GTVMRI and GTVONCO was 31.9 %, 54.5 % and 27.9 % respectively, and the entire GTVPATO was only fully encompassed in GTVONCO in 1 of 13 patients. However, after the addition of a clinical 5 mm margin the GTVPATO was fully encompassed in GTVONCO in 11 out of 13 patients.Conclusions: Despite modern hybrid imaging modalities, a mismatch between imaging and pathological defined tumor volumes was observed in all patients. A 5 mm clinical margin was sufficient to ensure inclusion of the entire pathological volume in 11 out of 13 patients.(c) 2023 The Authors. Published by Elsevier B.V. Radiotherapy and Oncology 180 (2023) 1-8 This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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| 28. |
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| 29. |
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| 30. |
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| 31. |
- Bridel, Claire, et al.
(författare)
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Diagnostic Value of Cerebrospinal Fluid Neurofilament Light Protein in Neurology : A Systematic Review and Meta-analysis
- 2019
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Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 76:9, s. 1035-1048
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Forskningsöversikt (refereegranskat)abstract
- Importance Neurofilament light protein (NfL) is elevated in cerebrospinal fluid (CSF) of a number of neurological conditions compared with healthy controls (HC) and is a candidate biomarker for neuroaxonal damage. The influence of age and sex is largely unknown, and levels across neurological disorders have not been compared systematically to date.Objectives To assess the associations of age, sex, and diagnosis with NfL in CSF (cNfL) and to evaluate its potential in discriminating clinically similar conditions.Data Sources PubMed was searched for studies published between January 1, 2006, and January 1, 2016, reporting cNfL levels (using the search terms neurofilament light and cerebrospinal fluid) in neurological or psychiatric conditions and/or in HC.Study Selection Studies reporting NfL levels measured in lumbar CSF using a commercially available immunoassay, as well as age and sex.Data Extraction and Synthesis Individual-level data were requested from study authors. Generalized linear mixed-effects models were used to estimate the fixed effects of age, sex, and diagnosis on log-transformed NfL levels, with cohort of origin modeled as a random intercept.Main Outcome and Measure The cNfL levels adjusted for age and sex across diagnoses.Results Data were collected for 10 059 individuals (mean [SD] age, 59.7 [18.8] years; 54.1% female). Thirty-five diagnoses were identified, including inflammatory diseases of the central nervous system (n = 2795), dementias and predementia stages (n = 4284), parkinsonian disorders (n = 984), and HC (n = 1332). The cNfL was elevated compared with HC in a majority of neurological conditions studied. Highest levels were observed in cognitively impaired HIV-positive individuals (iHIV), amyotrophic lateral sclerosis, frontotemporal dementia (FTD), and Huntington disease. In 33.3% of diagnoses, including HC, multiple sclerosis, Alzheimer disease (AD), and Parkinson disease (PD), cNfL was higher in men than women. The cNfL increased with age in HC and a majority of neurological conditions, although the association was strongest in HC. The cNfL overlapped in most clinically similar diagnoses except for FTD and iHIV, which segregated from other dementias, and PD, which segregated from atypical parkinsonian syndromes.Conclusions and Relevance These data support the use of cNfL as a biomarker of neuroaxonal damage and indicate that age-specific and sex-specific (and in some cases disease-specific) reference values may be needed. The cNfL has potential to assist the differentiation of FTD from AD and PD from atypical parkinsonian syndromes.
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| 32. |
- Chyrkin, Anton, 1984, et al.
(författare)
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Stability of External alpha-Al2O3 Scales on Alloy 602 CA at 1100-1200 A degrees C
- 2018
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Ingår i: Oxidation of Metals. - : Springer Science and Business Media LLC. - 1573-4889 .- 0030-770X. ; 90:1-2, s. 119-133
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Tidskriftsartikel (refereegranskat)abstract
- An external ultrathin alpha-Al2O3 scale grown on the Ni-base alloy 602 CA during air oxidation at 800 A degrees C was characterized by means of high-resolution TEM/EDX and electron diffraction. Alloy samples pre-oxidized at 800 A degrees C were subsequently exposed at 1100, 1150 and 1200 A degrees C for up to 100 h. Whereas the external alumina remained stable at 1100 A degrees C, with the increasing exposure temperature, the pre-grown alumina scale tended to break down resulting in an external chromia scale accompanied by internal alumina precipitation. The transition from external to internal Al oxidation was investigated using SEM/EDX/EBSD. The critical Al depletion at the scale-alloy interface during the post-exposure at 1100-1200 A degrees C was modeled using the CALPHAD-based thermodynamic-kinetic approach.
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| 33. |
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| 34. |
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| 35. |
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| 36. |
- Gond, Ritambhara, et al.
(författare)
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Non-flammable liquid electrolytes for safe batteries
- 2021
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Ingår i: Materials Horizons. - : Royal Society of Chemistry. - 2051-6347 .- 2051-6355. ; 8:11, s. 2913-2928
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Tidskriftsartikel (refereegranskat)abstract
- With continual increments in energy density gradually boosting the performance of rechargeable alkali metal ion (e.g. Li+, Na+, K+) batteries, their safe operation is of growing importance and needs to be considered during their development. This is essential, given the high-profile incidents involving battery fires as portrayed by the media. Such hazardous events result from exothermic chemical reactions occurring between the flammable electrolyte and the electrode material under abusive operating conditions. Some classes of non-flammable organic liquid electrolytes have shown potential towards safer batteries with minimal detrimental effect on cycling and, in some cases, even enhanced performance. This article reviews the state-of-the-art in non-flammable liquid electrolytes for Li-, Na- and K-ion batteries. It provides the reader with an overview of carbonate, ether and phosphate-based organic electrolytes, co-solvated electrolytes and electrolytes with flame-retardant additives as well as highly concentrated and locally highly concentrated electrolytes, ionic liquids and inorganic electrolytes. Furthermore, the functionality and purpose of the components present in typical non-flammable mixtures are discussed. Moreover, many non-flammable liquid electrolytes are shown to offer improved cycling stability and rate capability compared to conventional flammable liquid electrolytes.
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| 37. |
- Güneysu Özgür, Arzu, et al.
(författare)
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The effect of gamified robot-enhanced training on motor performance in chronic stroke survivors
- 2022
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Ingår i: Heliyon. - : Elsevier BV. - 2405-8440. ; 8:11, s. e11764-
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Tidskriftsartikel (refereegranskat)abstract
- Task-specific training constitutes a core element for evidence-based rehabilitation strategies targeted at improving upper extremity activity after stroke. Its combination with additional treatment strategies and neurotechnologybased solutions could further improve patients' outcomes. Here, we studied the effect of gamified robot-assisted upper limb motor training on motor performance, skill learning, and transfer with respect to a non-gamified control condition with a group of chronic stroke survivors. The results suggest that a gamified training strategy results in more controlled motor performance during the training phase, which is characterized by a higher accuracy (lower deviance), higher smoothness (lower jerk), but slower speed. The responder analyses indicated that mildly impaired patients benefited most from the gamification approach. In conclusion, gamified robot-assisted motor training, which is personalized to the individual capabilities of a patient, constitutes a promising investigational strategy for further improving motor performance after a stroke.
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| 38. |
- Ivanova, Darya, et al.
(författare)
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Survey of dust formed in the TEXTOR tokamak : structure and fuel retention
- 2009
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Ingår i: Physica scripta. T. - : Institute of Physics Publishing (IOPP). - 0281-1847. ; T138, s. 014025-
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Tidskriftsartikel (refereegranskat)abstract
- A detailed survey of erosion and deposition on plasma-facing components was performed in the TEXTOR tokamak. Co-deposits and dust particles were collected from graphite limiters and from several locations on the Inconel liner. The total amount of dust (loose material), originating mainly from carbon-rich co-deposits detached from the limiters and the liner, was around 2 g, with sizes from 0.1 mu m to 1 mm. The morphology and fuel retention was determined using microscopy methods, ion beam analysis and thermal desorption spectrometry. The study revealed differences in structure and fuel content between deposits from the toroidal and main poloidal limiters. There were also splashes, up to 1 mm in diameter, of molten metal (mainly nickel) on the toroidal limiters. Issues of the dust conversion factor (erosion-to-dust) are addressed and a comparison with results of previous dust surveys at TEXTOR is also briefly presented.
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| 39. |
- Johansson, Anna L., V, et al.
(författare)
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Were cancer patients worse off than the general population during the COVID-19 pandemic? : A population-based study from Norway, Denmark and Iceland during the pre-vaccination era
- 2023
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Ingår i: The Lancet Regional Health. - : Elsevier. - 2666-7762. ; 31
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Tidskriftsartikel (refereegranskat)abstract
- Background In a population-based setting, we investigated the risks of testing positive for SARS-CoV-2 and developing severe COVID-19 outcomes among cancer patients compared with the general population.Methods In nationwide cohorts, we identified all individuals in Norway, Denmark and Iceland who tested positive for SARS-CoV-2 or had a severe COVID-19 outcome (hospitalisation, intensive care, and death) from March until December 2020, using data from national health registries. We estimated standardised incidence ratios (SIRs) with 95% confidence intervals (CIs) comparing cancer patients with the general population.Findings During the first wave of the pandemic, cancer patients in Norway and Denmark had higher risks of testing SARS-CoV-2 positive compared to the general population. Throughout 2020, recently treated cancer patients were more likely to test SARS-CoV-2 positive. In Iceland, cancer patients experienced no increased risk of testing positive. The risk of COVID-19-related hospitalisation was higher among cancer patients diagnosed within one year of hospitalisation (Norway: SIR = 2.43, 95% CI 1.89-3.09; Denmark: 2.23, 1.96-2.54) and within five years (Norway: 1.58, 1.35-1.83; Denmark: 1.54, 1.42-1.66). Risks were higher in recently treated cancer patients and in those diagnosed with haematologic malignancies, colorectal or lung cancer. Risks of COVID-19-related intensive care and death were higher among cancer patients. Interpretation Cancer patients were at increased risk of testing positive for SARS-CoV-2 during the first pandemic wave when testing availability was limited, while relative risks of severe COVID-19 outcomes remained increased in cancer patients throughout 2020. Recent cancer treatment and haematologic malignancy were the strongest risk factors.
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| 40. |
- Kersten, CM, et al.
(författare)
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The Management of Asymptomatic Congenital Pulmonary Airway Malformation: Results of a European Delphi Survey
- 2022
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Ingår i: Children (Basel, Switzerland). - : MDPI AG. - 2227-9067. ; 9:8
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Tidskriftsartikel (refereegranskat)abstract
- Consensus on the optimal management of asymptomatic congenital pulmonary airway malformation (CPAM) is lacking, and comparison between studies remains difficult due to a large variety in outcome measures. We aimed to define a core outcome set (COS) for pediatric patients with an asymptomatic CPAM. An online, three-round Delphi survey was conducted in two stakeholder groups of specialized caregivers (surgeons and non-surgeons) in various European centers. Proposed outcome parameters were scored according to level of importance, and the final COS was established through consensus. A total of 55 participants (33 surgeons, 22 non-surgeons) from 28 centers in 13 European countries completed the three rounds and rated 43 outcome parameters. The final COS comprises seven outcome parameters: respiratory insufficiency, surgical complications, mass effect/mediastinal shift (at three time-points) and multifocal disease (at two time-points). The seven outcome parameters included in the final COS reflect the diversity in priorities among this large group of European participants. However, we recommend the incorporation of these outcome parameters in the design of future studies, as they describe measurable and validated outcomes as well as the accepted age at measurement.
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| 41. |
- Langeveld, H., et al.
(författare)
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Assessing Environmental Impacts of Short Rotation Coppice (SRC) Expansion: Model Definition and Preliminary Results
- 2012
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Ingår i: Bioenergy Research. - : Springer Science and Business Media LLC. - 1939-1234 .- 1939-1242. ; 5:3, s. 621-635
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Tidskriftsartikel (refereegranskat)abstract
- Short rotation coppice (SRC) systems can play a role as feedstock for bioenergy supply contributing to EU energy and climate policy targets. A scenario depicting intensive arable crop cultivation in a homogeneous landscape (lacking habitat structures) was compared to a scenario including SRC cultivation on 20 % of arable land. A range of indicators was selected to assess the consequences of SRC on soil, water and biodiversity, using data from the Rating-SRC project (Sweden and Germany). The results of the assessment were presented using spider diagrams. Establishment and use of SRC for bioenergy has both positive and negative effects. The former include increased carbon sequestration and reduced GHG emissions as well as reduced soil erosion, groundwater nitrate and surface runoff. SRC can be used in phytoremediation and improves plant and breeding bird biodiversity (exceptions: grassland and arable land species) but should not be applied in dry areas or on soils high in toxic trace elements (exception: cadmium). The scenario-based analysis was found useful for studying the consequences of SRC cultivation at larger scales. Limitations of the approach are related to data requirements and compatibility and its restricted ability to cover spatial diversity and dynamic processes. The findings should not be generalised beyond the representativeness of the data used.
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| 42. |
- Litnovsky, A., et al.
(författare)
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Experimental investigations of castellated monoblock structures in TEXTOR
- 2005
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Ingår i: Journal of Nuclear Materials. - : Elsevier BV. - 0022-3115 .- 1873-4820. ; 337-39:1-3, s. 917-921
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Tidskriftsartikel (refereegranskat)abstract
- To insure the thermo-mechanical durability of ITER it is planned to manufacture the castellated armour of the divertor i.e. to split the armour into cells [W. Daener et al., Fusion Eng. Des. 61T62 (2002) 61]. This will cause an increase of the surface area and may lead to carbon deposition and tritium accumulation in the gaps in between cells. To investigate the processes of deposition and fuel accumulation in gaps, a castellated test-limiter was exposed to the SOL plasma of TEXTOR. The geometry of castellation used was the same as proposed for the vertical divertor target in ITER [W. Daener et al., Fusion Eng. Des. 61T62 (2002) 61]. After exposure the limiter was investigated with various surface diagnostic techniques. Deposited layers containing carbon, hydrogen, deuterium and boron were found both on top plasma-facing surfaces and in the gaps. The amount of deuterium in the gaps was at least 30% of that found on the top surfaces.
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| 43. |
- Rana, Brinda K., et al.
(författare)
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Natural variation within the neuronal nicotinic acetylcholine receptor cluster on human chromosome 15q24 : influence on heritable autonomic traits in twin pairs
- 2009
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Ingår i: Journal of Pharmacology and Experimental Therapeutics. - : American Society for Pharmacology & Experimental Therapeutics (ASPET). - 0022-3565 .- 1521-0103. ; 331:2, s. 419-428
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Tidskriftsartikel (refereegranskat)abstract
- Nicotinic acetylcholine receptors (nAChRs) are combinations of subunits arranged as pentamers encircling a central cation channel. At least nine α and four β subunits are expressed in the central and peripheral nervous systems; their presence in autonomic ganglia, the adrenal medulla, and central nervous system, with accompanying responses elicited by nicotinic agonists, point to their involvement in cardiovascular homeostasis. nAChRs formed by α3, α5, and β4 subunits may regulate blood pressure (BP) by mediating release of catestatin, the endogenous nicotinic antagonist fragment of chromogranin A (CHGA) and potent inhibitor of catecholamine secretion. Genes encoding these subunits (CHRNA3, CHRNA5, and CHRNB4) are clustered on human chromosome 15q24. Because variation in this cluster may alter autonomic regulation of BP, we sequenced ∼15 kilobase pairs in 15q24 containing their coding and 5′- and 3′-untranslated regions in 80 individuals. We identified 63 variants: 25 in coding regions of CHRNA3, CHRNA5, and CHRNB4 and 48 noncoding single-nucleotide polymorphisms (SNPs). Haplotype frequencies varied across ethnic populations. We assessed the contribution of six SNPs in the putative catestatin binding region of CHRNA3 and CHRNB4 to autonomic traits. In twins, catestatin and BP were heritable. CHRNA3 SNPs and haplotypes containing K95K (G285A) associated with circulating plasma catestatin, epinephrine levels, as well as systolic BP, suggesting altered coupling of the nAChRs to BP. Studies of chromaffin cells in vitro reveal that nicotinic agonist stimulation releases catecholamines and CHGA, a process augmented by overexpression of CHRNA3 and blocked by catestatin. These cellular events suggest a homeostatic mechanism underlying the pleiotropic actions of CHRNA3 genetic variation on autonomic function observed in twins.
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| 44. |
- Rubel, Marek J., et al.
(författare)
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An overview of fuel retention and morphology in a castellated tungsten limiter
- 2008
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Ingår i: Fusion engineering and design. - : Elsevier BV. - 0920-3796 .- 1873-7196. ; 83:7-9, s. 1049-1053
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Tidskriftsartikel (refereegranskat)abstract
- A castellated tungsten test limiter composed of detachable segments was exposed to plasma discharges in the TEXTOR to kamak operated with graphite main limiters. Dismantling of the limiter enabled the analysis Of Surfaces located inside the castellation, The emphasis was on the determination of: (i) deposition and fuel retention; (ii) material mixing and new Compound formation on plasma-facing Surfaces and in the grooves of castellation. The investigation performed by means of accelerator-based ion beam analysis methods, microscopy and X-ray diffraction has brought several essential results: (i) deuterium retention oil plasma-facing Surfaces and in the castellation of metal PFC is strongly related to the co-deposition with carbon; (ii) both carbon and deuterium are detected only in narrow belts, a few millimetre broad, clown the gap with the decay length of around 1.2-1.8 mm; (iii) the presence of copper droplets and tungsten oxide (WO(2)) has been identified in the gaps. Different pathways leading to the oxide formation are considered.
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| 45. |
- Salian, Girish D., et al.
(författare)
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Understanding the electrochemical and interfacial behaviour of sulfolane-based electrolytes in LiNi0.5Mn1.5O4-graphite full-cells
- 2023
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Ingår i: Batteries & Supercaps. - : John Wiley & Sons. - 2566-6223. ; n/a:n/a
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Tidskriftsartikel (refereegranskat)abstract
- An ethylene carbonate-free electrolyte composed of 1 M lithium bis(fluorosulfonyl) imide (LiFSI) in sulfolane (SL) is studied here for LiNi0.5Mn1.5O4-graphite full-cells. An important focus on the evaluation of the anodic stability of the SL electrolyte and the passivation layers formed on LNMO and graphite is being analysed along with intermittent current interruption (ICI) technique to observe the resistance while cycling. The results show that the sulfolane electrolyte shows more degradation at higher potentials unlike previous reports which suggested higher oxidative stability. However, the passivation layers formed due to this electrolyte degradation prevents further degradation. The resistance measurements show that major resistance arises from the cathode. The pressure evolution during the formation cycles suggests that there is lower gas evolution with sulfolane electrolyte than in the conventional electrolyte. The study opens a new outlook on the sulfolane based electrolyte especially regarding its oxidative/anodic stability.
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| 46. |
- Sergienko, G., et al.
(författare)
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Experience with bulk tungsten test-limiters under high heat loads : melting and melt layer propagation
- 2007
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Ingår i: Physica Scripta. - 0031-8949 .- 1402-4896. ; T128, s. 81-86
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Tidskriftsartikel (refereegranskat)abstract
- The paper provides an overview of processes and underlying physics governing tungsten melt erosion in the fusion plasma environment. Experiments with three different bulk tungsten test-limiters were performed in TEXTOR: (i) thermally insulated solid plate fixed on a graphite roof-like limiter heated up by the plasma to the melting point, (ii) macro-brush of the ITER-relevant castellated structure and (iii) lamellae structure developed for the JET divertor. The main objectives were to determine the metal surface damage, the formation of the melt layer and its motion in the magnetic field. PHEMOBRID-3D and MEMOS-1.5D numerical codes were used to simulate the experiment with the roof-like test-limiter. Both experiments and simulation showed that the melting of tungsten can lead to a large material redistribution due to thermo-electron emission currents without ejection of molten material to the plasma.
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| 47. |
- Snoek, KG, et al.
(författare)
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Standardized Postnatal Management of Infants with Congenital Diaphragmatic Hernia in Europe: The CDH EURO Consortium Consensus - 2015 Update
- 2016
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Ingår i: Neonatology. - : S. Karger AG. - 1661-7819 .- 1661-7800. ; 110:1, s. 66-74
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Tidskriftsartikel (refereegranskat)abstract
- In 2010, the congenital diaphragmatic hernia (CDH) EURO Consortium published a standardized neonatal treatment protocol. Five years later, the number of participating centers has been raised from 13 to 22. In this article the relevant literature is updated, and consensus has been reached between the members of the CDH EURO Consortium. Key updated recommendations are: (1) planned delivery after a gestational age of 39 weeks in a high-volume tertiary center; (2) neuromuscular blocking agents to be avoided during initial treatment in the delivery room; (3) adapt treatment to reach a preductal saturation of between 80 and 95% and postductal saturation >70%; (4) target PaCO<sub>2</sub> to be between 50 and 70 mm Hg; (5) conventional mechanical ventilation to be the optimal <i>initial</i> ventilation strategy, and (6) intravenous sildenafil to be considered in CDH patients with severe pulmonary hypertension. This article represents the current opinion of all consortium members in Europe for the optimal neonatal treatment of CDH.
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| 48. |
- Timmer, Stefan A J, et al.
(författare)
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Carriers of the hypertrophic cardiomyopathy MYBPC3 mutation are characterized by reduced myocardial efficiency in the absence of hypertrophy and microvascular dysfunction
- 2011
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Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 13:12, s. 1283-1289
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Tidskriftsartikel (refereegranskat)abstract
- AIMS:Next to left ventricular (LV) hypertrophy, hypertrophic cardiomyopathy (HCM) is characterized by microvascular dysfunction and reduced myocardial external efficiency (MEE). Insights into the presence of these abnormalities as early markers of disease are of clinical importance in risk stratification, and development of therapeutic approaches. Therefore, the aim was to investigate myocardial perfusion and energetics in genotype-positive, phenotype-negative HCM subjects (carriers).METHODS AND RESULTS:Fifteen carriers of an MYBPC3 mutation underwent [15O]water positron emission tomography (PET) to assess myocardial blood flow (MBF). [11C]acetate PET was performed to obtain myocardial oxygen consumption (MVO2). By use of cardiovascular magnetic resonance imaging, LV volumes and mass were defined to calculate MEE, i.e. the ratio between external work and MVO2. Eleven healthy, genotype-negative, family relatives underwent similar scanning protocols to serve as a control group. Left ventricular mass was comparable between carriers and controls (93 ± 25 vs. 99 ± 21 g, P= 0.85), as was MBF at rest (1.19 ± 0.34 vs. 1.18 ± 0.32 mL min−1 g−1, P= 0.92), and during hyperaemia (3.87 ± 0.75 vs. 3.96 ± 0.86 mL min−1 g−1, P= 0.77). Myocardial oxygen consumption averaged 0.137 ± 0.057 mL min−1 g−1 in carriers and was not significantly different from controls (0.125 ± 0.043 mL min−1 g−1, P= 0.29). Cardiac work, however, was slightly reduced in carriers (7398 ± 1384 vs. 9139 ± 2484 mmHg mL in controls, P= 0.08). As a consequence, MEE was significantly decreased in carriers (27 ± 10 vs. 36 ± 8% in controls, P= 0.02).CONCLUSION:Carriers display reduced myocardial work generation in relation to oxygen consumption, in the absence of hypertrophy and flow abnormalities. Hence, impaired myocardial energetics may constitute a primary component of HCM pathogenesis.
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| 49. |
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