| 1. |
- Adams, Robin, et al.
(författare)
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What is the word for 'Engineering' in Swedish : Swedish students conceptions of their discipline
- 2007
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Engineering education in Sweden – as in the rest of the world – is experiencing a decline in student interest. There are concerns about the ways in which students think about engineering education, why they join an academic programme in engineering, and why they persist in their studies. In this context the aims of the Nationellt ämnesdidaktiskt Centrum för Teknikutbildning i Studenternas Sammanhang project (CeTUSS) is to investigate the student experience and to identify and support a continuing network of interested researchers, as well as in building capacity for disciplinary pedagogic investigation. The Stepping Stones project brings together these interests in a multi-researcher, multi-institutional study that investigates how tudents and academic staff perceive engineering in Sweden and in Swedish education. The first results of that project are reported here. As this study is situated uniquely in Swedish education, it allows for exploration of “a Swedish perspective” on conceptions of engineering. The Stepping Stones project was based on a model of research capacity-building previously instantiated in the USA and Australia (Fincher & Tenenberg, 2006).
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| 2. |
- Bergamaschi, Peter, et al.
(författare)
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High-resolution inverse modelling of European CH4emissions using the novel FLEXPART-COSMO TM5 4DVAR inverse modelling system
- 2022
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Ingår i: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 22:20, s. 13243-13268
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Tidskriftsartikel (refereegranskat)abstract
- We present a novel high-resolution inverse modelling system ("FLEXVAR") based on FLEXPARTCOSMO back trajectories driven by COSMO meteorological fields at 7 km×7 km resolution over the European COSMO-7 domain and the four-dimensional variational (4DVAR) data assimilation technique. FLEXVAR is coupled offline with the global inverse modelling system TM5-4DVAR to provide background mole fractions ("baselines") consistent with the global observations assimilated in TM5-4DVAR. We have applied the FLEXVAR system for the inverse modelling of European CH4 emissions in 2018 using 24 stations with in situ measurements, complemented with data from five stations with discrete air sampling (and additional stations outside the European COSMO-7 domain used for the global TM5-4DVAR inversions). The sensitivity of the FLEXVAR inversions to different approaches to calculate the baselines, different parameterizations of the model representation error, different settings of the prior error covariance parameters, different prior inventories, and different observation data sets are investigated in detail. Furthermore, the FLEXVAR inversions are compared to inversions with the FLEXPART extended Kalman filter ("FLExKF") system and with TM5-4DVAR inversions at 1° × 1° resolution over Europe. The three inverse modelling systems show overall good consistency of the major spatial patterns of the derived inversion increments and in general only relatively small differences in the derived annual total emissions of larger country regions. At the same time, the FLEXVAR inversions at 7 km × 7 km resolution allow the observations to be better reproduced than the TM5-4DVAR simulations at 1° × 1°. The three inverse models derive higher annual total CH4 emissions in 2018 for Germany, France, and BENELUX compared to the sum of anthropogenic emissions reported to UNFCCC and natural emissions estimated from the Global Carbon Project CH4 inventory, but the uncertainty ranges of top-down and bottom-up total emission estimates overlap for all three country regions. In contrast, the top-down estimates for the sum of emissions from the UK and Ireland agree relatively well with the total of anthropogenic and natural bottom-up inventories.
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| 3. |
- Bergamaschi, Peter, et al.
(författare)
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Inverse modelling of European CH4 emissions during 2006–2012 using different inverse models and reassessed atmospheric observations
- 2018
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Ingår i: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7324. ; 18:2, s. 901-920
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Tidskriftsartikel (refereegranskat)abstract
- We present inverse modelling (top down) estimates of European methane (CH4) emissions for 2006–2012 based on a new quality-controlled and harmonised in situ data set from 18 European atmospheric monitoring stations. We applied an ensemble of seven inverse models and performed four inversion experiments, investigating the impact of different sets of stations and the use of a priori information on emissions. The inverse models infer total CH4 emissions of 26.8 (20.2–29.7) Tg CH4 yr−1 (mean, 10th and 90th percentiles from all inversions) for the EU-28 for 2006–2012 from the four inversion experiments. For comparison, total anthropogenic CH4 emissions reported to UNFCCC (bottom up, based on statistical data and emissions factors) amount to only 21.3 Tg CH4 yr−1 (2006) to 18.8 Tg CH4 yr−1 (2012). A potential explanation for the higher range of top-down estimates compared to bottom-up inventories could be the contribution from natural sources, such as peatlands, wetlands, and wet soils. Based on seven different wetland inventories from the Wetland and Wetland CH4 Inter-comparison of Models Project (WETCHIMP), total wetland emissions of 4.3 (2.3–8.2) Tg CH4 yr−1 from the EU-28 are estimated. The hypothesis of significant natural emissions is supported by the finding that several inverse models yield significant seasonal cycles of derived CH4 emissions with maxima in summer, while anthropogenic CH4 emissions are assumed to have much lower seasonal variability. Taking into account the wetland emissions from the WETCHIMP ensemble, the top-down estimates are broadly consistent with the sum of anthropogenic and natural bottom-up inventories. However, the contribution of natural sources and their regional distribution remain rather uncertain. Furthermore, we investigate potential biases in the inverse models by comparison with regular aircraft profiles at four European sites and with vertical profiles obtained during the Infrastructure for Measurement of the European Carbon Cycle (IMECC) aircraft campaign. We present a novel approach to estimate the biases in the derived emissions, based on the comparison of simulated and measured enhancements of CH4 compared to the background, integrated over the entire boundary layer and over the lower troposphere. The estimated average regional biases range between −40 and 20 % at the aircraft profile sites in France, Hungary and Poland.
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| 4. |
- Gaudet, Mia M., et al.
(författare)
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Common Genetic Variants and Modification of Penetrance of BRCA2-Associated Breast Cancer
- 2010
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 6:10
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Tidskriftsartikel (refereegranskat)abstract
- The considerable uncertainty regarding cancer risks associated with inherited mutations of BRCA2 is due to unknown factors. To investigate whether common genetic variants modify penetrance for BRCA2 mutation carriers, we undertook a two-staged genome-wide association study in BRCA2 mutation carriers. In stage 1 using the Affymetrix 6.0 platform, 592,163 filtered SNPs genotyped were available on 899 young (, 40 years) affected and 804 unaffected carriers of European ancestry. Associations were evaluated using a survival-based score test adjusted for familial correlations and stratified by country of the study and BRCA2*6174delT mutation status. The genomic inflation factor (lambda) was 1.011. The stage 1 association analysis revealed multiple variants associated with breast cancer risk: 3 SNPs had p-values, 10 25 and 39 SNPs had p-values<10(-4). These variants included several previously associated with sporadic breast cancer risk and two novel loci on chromosome 20 (rs311499) and chromosome 10 (rs16917302). The chromosome 10 locus was in ZNF365, which contains another variant that has recently been associated with breast cancer in an independent study of unselected cases. In stage 2, the top 85 loci from stage 1 were genotyped in 1,264 cases and 1,222 controls. Hazard ratios (HR) and 95% confidence intervals (CI) for stage 1 and 2 were combined and estimated using a retrospective likelihood approach, stratified by country of residence and the most common mutation, BRCA2*6174delT. The combined per allele HR of the minor allele for the novel loci rs16917302 was 0.75 (95% CI 0.66-0.86, p = 3: 8 x 10(-5)) and for rs311499 was 0.72 (95% CI 0.61-0.85, p = 6: 6 x 10(-5)). FGFR2 rs2981575 had the strongest association with breast cancer risk (per allele HR = 1.28, 95% CI 1.18-1.39, p = 1: 2 x 10(-8)). These results indicate that SNPs that modify BRCA2 penetrance identified by an agnostic approach thus far are limited to variants that also modify risk of sporadic BRCA2 wild-type breast cancer.
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| 5. |
- Hall, Stephen C.L., et al.
(författare)
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The interaction of styrene maleic acid copolymers with phospholipids in Langmuir monolayers, vesicles and nanodiscs; a structural study
- 2022
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Ingår i: Journal of Colloid and Interface Science. - : Elsevier BV. - 0021-9797. ; 625, s. 220-236
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Tidskriftsartikel (refereegranskat)abstract
- Hypothesis: Self-assembly of amphipathic styrene maleic acid copolymers with phospholipids in aqueous solution results in the formation of ‘nanodiscs’ containing a planar segment of phospholipid bilayer encapsulated by a polymer belt. Recently, studies have reported that lipids rapidly exchange between both nanodiscs in solution and external sources of lipids. Outstanding questions remain regarding details of polymer-lipid interactions, factors influencing lipid exchange and structural effects of such exchange processes. Here, the dynamic behaviour of nanodiscs is investigated, specifically the role of membrane charge and polymer chemistry. Experiments: Two model systems are investigated: fluorescently labelled phospholipid vesicles, and Langmuir monolayers of phospholipids. Using fluorescence spectroscopy and time-resolved neutron reflectometry, the membrane potential, monolayer structure and composition are monitored with respect to time upon polymer and nanodisc interactions. Findings: In the presence of external lipids, polymer chains embed throughout lipid membranes, the extent of which is governed by the net membrane charge. Nanodiscs stabilised by three different polymers will all exchange lipids and polymer with monolayers to differing extents, related to the properties of the stabilising polymer belt. These results demonstrate the dynamic nature of nanodiscs which interact with the local environment and are likely to deposit both lipids and polymer at all stages of use.
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| 6. |
- Koettgen, Anna, et al.
(författare)
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Genome-wide association analyses identify 18 new loci associated with serum urate concentrations
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:2, s. 145-154
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Tidskriftsartikel (refereegranskat)abstract
- Elevated serum urate concentrations can cause gout, a prevalent and painful inflammatory arthritis. By combining data from >140,000 individuals of European ancestry within the Global Urate Genetics Consortium (GUGC), we identified and replicated 28 genome-wide significant loci in association with serum urate concentrations (18 new regions in or near TRIM46, INHBB, SEMBT1, TMEM171, VEGFA, BAZ1B, PRKAG2, STC1, HNF4G, A1CF, ATXN2, UBE2Q2, IGF1R, NFAT5, MAF, HLF, ACVR1B-ACVRL1 and B3GNT4). Associations for many of the loci were of similar magnitude in individuals of non-European ancestry. We further characterized these loci for associations with gout, transcript expression and the fractional excretion of urate. Network analyses implicate the inhibins-activins signaling pathways and glucose metabolism in systemic urate control. New candidate genes for serum urate concentration highlight the importance of metabolic control of urate production and excretion, which may have implications for the treatment and prevention of gout.
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| 7. |
- Law, Philip J., et al.
(författare)
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Association analyses identify 31 new risk loci for colorectal cancer susceptibility
- 2019
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide, and has a strong heritable basis. We report a genome-wide association analysis of 34,627 CRC cases and 71,379 controls of European ancestry that identifies SNPs at 31 new CRC risk loci. We also identify eight independent risk SNPs at the new and previously reported European CRC loci, and a further nine CRC SNPs at loci previously only identified in Asian populations. We use in situ promoter capture Hi-C (CHi-C), gene expression, and in silico annotation methods to identify likely target genes of CRC SNPs. Whilst these new SNP associations implicate target genes that are enriched for known CRC pathways such as Wnt and BMP, they also highlight novel pathways with no prior links to colorectal tumourigenesis. These findings provide further insight into CRC susceptibility and enhance the prospects of applying genetic risk scores to personalised screening and prevention.
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| 8. |
- Louca, Panayiotis, et al.
(författare)
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The secondary bile acid isoursodeoxycholate correlates with post-prandial lipemia, inflammation, and appetite and changes post-bariatric surgery
- 2023
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Ingår i: Cell Reports Medicine. - 2666-3791. ; 4:4
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Tidskriftsartikel (refereegranskat)abstract
- Primary and secondary bile acids (BAs) influence metabolism and inflammation, and the gut microbiome modulates levels of BAs. We systematically explore the host genetic, gut microbial, and habitual dietary contribution to a panel of 19 serum and 15 stool BAs in two population-based cohorts (TwinsUK, n = 2,382; ZOE PREDICT-1, n = 327) and assess changes post-bariatric surgery and after nutritional interventions. We report that BAs have a moderately heritable genetic component, and the gut microbiome accurately predicts their levels in serum and stool. The secondary BA isoursodeoxycholate (isoUDCA) can be explained mostly by gut microbes (area under the receiver operating characteristic curve [AUC] = ∼80%) and associates with post-prandial lipemia and inflammation (GlycA). Furthermore, circulating isoUDCA decreases significantly 1 year after bariatric surgery (β = −0.72, p = 1 × 10−5) and in response to fiber supplementation (β = −0.37, p < 0.03) but not omega-3 supplementation. In healthy individuals, isoUDCA fasting levels correlate with pre-meal appetite (p < 1 × 10−4). Our findings indicate an important role for isoUDCA in lipid metabolism, appetite, and, potentially, cardiometabolic risk.
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| 9. |
- Mak, Elijah, et al.
(författare)
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In vivo coupling of tau pathology and cortical thinning in Alzheimer's disease
- 2018
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Ingår i: Alzheimer's & dementia (Amsterdam, Netherlands). - : Wiley. - 2352-8729. ; 10, s. 678-687
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The deposition of neurofibrillary tangles in neurodegenerative disorders is associated with neuronal loss on autopsy; however, their in vivo associations with atrophy across the continuum of Alzheimer's disease (AD) remain unclear.Methods: We estimated cortical thickness, tau ([18F]-AV-1451), and amyloid β (Aβ) status ([11C]-PiB) in 47 subjects who were stratified into Aβ- (14 healthy controls and six mild cognitive impairment-Aβ-) and Aβ+ (14 mild cognitive impairment-Aβ+ and 13 AD) groups.Results: Compared with the Aβ- group, tau was increased in widespread regions whereas cortical thinning was restricted to the temporal cortices. Increased tau binding was associated with cortical thinning in each Aβ group. Locally, regional tau was associated with temporoparietal atrophy.Discussion: These findings position tau as a promising therapeutic target. Further studies are needed to elucidate the casual relationships between tau pathology and trajectories of atrophy in AD.
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| 10. |
- Stolk, Lisette, et al.
(författare)
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Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways
- 2012
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:3, s. 260-268
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Tidskriftsartikel (refereegranskat)abstract
- To newly identify loci for age at natural menopause, we carried out a meta-analysis of 22 genome-wide association studies (GWAS) in 38,968 women of European descent, with replication in up to 14,435 women. In addition to four known loci, we identified 13 loci newly associated with age at natural menopause (at P < 5 × 10(-8)). Candidate genes located at these newly associated loci include genes implicated in DNA repair (EXO1, HELQ, UIMC1, FAM175A, FANCI, TLK1, POLG and PRIM1) and immune function (IL11, NLRP11 and PRRC2A (also known as BAT2)). Gene-set enrichment pathway analyses using the full GWAS data set identified exoDNase, NF-κB signaling and mitochondrial dysfunction as biological processes related to timing of menopause.
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| 11. |
- Warren, Wesley C, et al.
(författare)
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The genome of a songbird
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7289, s. 757-762
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Tidskriftsartikel (refereegranskat)abstract
- The zebra finch is an important model organism in several fields with unique relevance to human neuroscience. Like other songbirds, the zebra finch communicates through learned vocalizations, an ability otherwise documented only in humans and a few other animals and lacking in the chicken-the only bird with a sequenced genome until now. Here we present a structural, functional and comparative analysis of the genome sequence of the zebra finch (Taeniopygia guttata), which is a songbird belonging to the large avian order Passeriformes. We find that the overall structures of the genomes are similar in zebra finch and chicken, but they differ in many intrachromosomal rearrangements, lineage-specific gene family expansions, the number of long-terminal-repeat-based retrotransposons, and mechanisms of sex chromosome dosage compensation. We show that song behaviour engages gene regulatory networks in the zebra finch brain, altering the expression of long non-coding RNAs, microRNAs, transcription factors and their targets. We also show evidence for rapid molecular evolution in the songbird lineage of genes that are regulated during song experience. These results indicate an active involvement of the genome in neural processes underlying vocal communication and identify potential genetic substrates for the evolution and regulation of this behaviour.
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