| 1. |
- Shungin, Dmitry, et al.
(författare)
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New genetic loci link adipose and insulin biology to body fat distribution.
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 187-378
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Tidskriftsartikel (refereegranskat)abstract
- Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
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| 2. |
- Everitt, Turid, et al.
(författare)
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The Genomic Basis of Adaptation to High Elevations in Africanized Honey Bees
- 2023
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Ingår i: Genome Biology and Evolution. - : Oxford University Press. - 1759-6653. ; 15:9
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Tidskriftsartikel (refereegranskat)abstract
- A range of different genetic architectures underpin local adaptation in nature. Honey bees (Apis mellifera) in the Eastern African Mountains harbor high frequencies of two chromosomal inversions that likely govern adaptation to this high-elevation habitat. In the Americas, honey bees are hybrids of European and African ancestries and adaptation to latitudinal variation in climate correlates with the proportion of these ancestries across the genome. It is unknown which, if either, of these forms of genetic variation governs adaptation in honey bees living at high elevations in the Americas. Here, we performed whole-genome sequencing of 29 honey bees from both high- and low-elevation populations in Colombia. Analysis of genetic ancestry indicated that both populations were predominantly of African ancestry, but the East African inversions were not detected. However, individuals in the higher elevation population had significantly higher proportions of European ancestry, likely reflecting local adaptation. Several genomic regions exhibited particularly high differentiation between highland and lowland bees, containing candidate loci for local adaptation. Genes that were highly differentiated between highland and lowland populations were enriched for functions related to reproduction and sperm competition. Furthermore, variation in levels of European ancestry across the genome was correlated between populations of honey bees in the highland population and populations at higher latitudes in South America. The results are consistent with the hypothesis that adaptation to both latitude and elevation in these hybrid honey bees are mediated by variation in ancestry at many loci across the genome.
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| 3. |
- Forssén, Jens, 1968, et al.
(författare)
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Auralization model for the perceptual evaluation of tyre–road noise
- 2018
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Ingår i: Applied Acoustics. - : Elsevier BV. - 0003-682X .- 1872-910X. ; 132, s. 232-242
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Tidskriftsartikel (refereegranskat)abstract
- Due to improvements in combustion-engines and use of electric-engines for cars, tyre noise has become the prominent noise source also at lower speeds. Models exist that simulate the noise produced by a rolling tyre, as do models that auralize different traffic situations from basic data. In this paper, a novel auralization method is introduced, with the purpose to enable synthesis of useful car pass-by sound signals for various situations. The method is based on an established model for tyre noise levels (SPERoN) that is combined with a validated auralization tool (LISTEN). In the LISTEN approach, source signals for tyre–road interaction and propulsion are produced from data based on recorded pass-by sounds. In the combined model, the tyre–road interaction data is shaped by the spectra estimated in SPERoN and synthesized back into a pass-by signal. The combined model is made to agree spectrally with measurements for a receiver at 7.5 m distance. Psychoacoustic judgments were used to compare the modelled signals with recorded signals, and the pass-by sounds for a given listener position showed promising quality and accuracy with respect to perceived pleasantness.
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| 4. |
- Gimpel, Thomas, et al.
(författare)
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Electrochemical Carbon Dioxide Reduction on Femtosecond Laser-Processed Copper Electrodes : Effect on the Liquid Products by Structuring and Doping
- 2021
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Ingår i: ACS Applied Energy Materials. - : American Chemical Society (ACS). - 2574-0962. ; 4:6, s. 5927-5934
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Tidskriftsartikel (refereegranskat)abstract
- A femtosecond laser process is presented increasing the surface area of copper electrocatalysts for an electrochemical CO2 reduction reaction (CO2RR). The laser treatment allows us to tune the surface morphology and the chemical composition of the copper electrocatalysts. This tunability is used to correlate the role of the surface area and catalyst dopants with the selectivity of the CO2RR. The liquid products of the CO2RR are monitored through ex situ nuclear magnetic resonance spectroscopy. The products’ distribution shows that the electrode surface area plays a key role in the electrochemical conversion of CO2 into multicarbon liquid products. We show that sulfur dopants boost the production of formate. Remarkably, by co-doping sulfur and fluoride, we show that the chalcogenide dopant counteracts the known boosting effect of fluoride to convert CO2 into multicarbon products. Oxygen doping in the range of 2–19 atom % does not significantly affect the distribution of liquid products from CO2 electroreduction. In a broad perspective, this work highlights the potential of the femtosecond laser process to fine-tune surfaces to produce photo- and electrocatalyst materials.
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| 5. |
- Hartkopf, Andreas D., et al.
(författare)
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Disseminated tumour cells from the bone marrow of early breast cancer patients : Results from an international pooled analysis
- 2021
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Ingår i: European Journal of Cancer. - : Elsevier BV. - 0959-8049. ; 154, s. 128-137
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Presence of disseminated tumour cells (DTCs) in the bone marrow (BM) has been described as a surrogate of residual disease in patients with early breast cancer (EBC). PADDY (Pooled Analysis of DTC Detection in Early Breast Cancer) is a large international analysis of pooled data that aimed to assess the prognostic impact of DTCs in patients with EBC. Experimental design: Individual patient data were collected from 11 centres. Patients with EBC and available follow-up data in whom BM sampling was performed at the time of primary diagnosis before receiving any anticancer treatment were eligible. DTCs were identified by antibody staining against epithelial cytokeratins. Multivariate Cox regression was used to compare the survival of DTC-positive versus DTC-negative patients. Results: In total, 10,307 patients were included. Of these, 2814 (27.3%) were DTC-positive. DTC detection was associated with higher tumour grade, larger tumour size, nodal positivity, oestrogen receptor and progesterone receptor negativity, and HER2 positivity (all p < 0.001). Multivariate analyses showed that DTC detection was an independent prognostic marker for overall survival, disease-free survival and distant disease-free survival with hazard ratios (HR) and 95% confidence intervals (CI) of 1.23 (95% CI: 1.06–1.43, p = 0.006), 1.30 (95% CI: 1.12–1.52, p < 0.001) and 1.30 (95% CI: 1.08–1.56, p = 0.006), respectively. There was no association between locoregional relapse-free survival and DTC detection (HR 1.21; 95% CI 0.68–2.16; p = 0.512). Conclusions: DTCs in the BM represent an independent prognostic marker in patients with EBC. The heterogeneous metastasis-initiating potential of DTCs is consistent with the concept of cancer dormancy.
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| 6. |
- Hibar, Derrek P., et al.
(författare)
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Novel genetic loci associated with hippocampal volume
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r(g) = -0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
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| 7. |
- Hoffmann, Alice, 1983, et al.
(författare)
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Auralization of simulated tyre noise: Psychoacoustic validation of a combined model
- 2019
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Ingår i: Applied Acoustics. - : Elsevier BV. - 0003-682X .- 1872-910X. ; 145, s. 220-227
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Tidskriftsartikel (refereegranskat)abstract
- Due to improvements on combustion-engines and electric-engines for cars, tyre noise has become the prominent noise source at low and medium speeds. Models exist that simulate the noise produced by a rolling tyre, as do models that auralize different traffic situations from a basic data set. In this paper, an established model for tyre noise (SPERoN) is combined with an auralization tool. The combined model can predict the spectrum of the sound at 7.5 m, as well as reproduce the sound for a given listener position. The auralization uses a methodology where recorded sounds are converted to source signals for engine and tyre/road-interaction. These can be shaped by the spectra estimated in SPERoN and synthesized back into a pass-by signal. Psychoacoustic judgements were used to compare the modelled signals with recorded signals. To see how well the modelled signals match the real recorded signals for perception, two listening-tests were performed. The simulated and recorded signals were rated by pleasantness, loudness, roughness and sharpness using semantic differentials. It was found that responses for simulated and recorded signals correlate for all cases, but rankings could not be reproduced exactly. The model can be further improved to be more applicable for listening tests.
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| 8. |
- Hoffmann, Alice, 1983, et al.
(författare)
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Perception of Tyre Noise: Can Tyre Noise be Differentiated and Characterized by the Perception of a Listener Outside the Car?
- 2016
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Ingår i: Acta Acustica united with Acustica. - : Wissenschaftliche Verlagsgesellschaft mbH. - 1610-1928 .- 1861-9959. ; 102:6, s. 992-998
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Tidskriftsartikel (refereegranskat)abstract
- When constructing a tyre, it is of importance that improvements and planned changes are not only physically measurable, but that they also can be perceived by a listener. Tyre/road noise becomes a more important focus area, especially with the growing market of electric vehicles. In the design of tyre/road sound, there are three main aims: to reduce the overall sound level, to increase pleasantness and to do so still maintaining the carried information about e.g. driving conditions. To be able to do this, an understanding of how physical changes in a tyre are reflected in the perception of the same tyre is essential. In the present study, the aim is thus to determine if the rolling noise of a tyre can be both differentiated and characterized by its perceptual qualities. The focus is on the perception of the sound outside the car, perceived by, for example, a pedestrian. Listeners have judged different road tyre combinations and their perception in terms of their emotional responses (pleasantness, activation and stress) and their psychoacoustic responses (loudnes s, sharpness, roughness, and pitch). The results confirmed that rolling noise can be perceptually differentiated. Further, it is possible to differentiate between the effects of the street and the effects of the tyre on all emotional and most psychoacoustic parameters. The results suggest that changes to both road surfaces and tyres can affect both emotional and psychoacoustic perceptual qualities.
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| 9. |
- Hoffmann, Ute A., et al.
(författare)
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The role of the 5' sensing function of ribonuclease E in cyanobacteria
- 2024
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Ingår i: RNA Biology. - : Informa UK Limited. - 1547-6286 .- 1555-8584. ; 21:1, s. 1-18
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Tidskriftsartikel (refereegranskat)abstract
- RNA degradation is critical for synchronising gene expression with changing conditions in prokaryotic and eukaryotic organisms. In bacteria, the preference of the central ribonucleases RNase E, RNase J and RNase Y for 5'-monophosphorylated RNAs is considered important for RNA degradation. For RNase E, the underlying mechanism is termed 5' sensing, contrasting to the alternative 'direct entry' mode, which is independent of monophosphorylated 5' ends. Cyanobacteria, such as Synechocystis sp. PCC 6803 (Synechocystis), encode RNase E and RNase J homologues. Here, we constructed a Synechocystis strain lacking the 5' sensing function of RNase E and mapped on a transcriptome-wide level 283 5'-sensing-dependent cleavage sites. These included so far unknown targets such as mRNAs encoding proteins related to energy metabolism and carbon fixation. The 5' sensing function of cyanobacterial RNase E is important for the maturation of rRNA and several tRNAs, including tRNAGluUUC. This tRNA activates glutamate for tetrapyrrole biosynthesis in plant chloroplasts and in most prokaryotes. Furthermore, we found that increased RNase activities lead to a higher copy number of the major Synechocystis plasmids pSYSA and pSYSM. These results provide a first step towards understanding the importance of the different target mechanisms of RNase E outside Escherichia coli.
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| 10. |
- Hou, Liping, et al.
(författare)
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Genome-wide association study of 40,000 individuals identifies two novel loci associated with bipolar disorder.
- 2016
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Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 25:15, s. 3383-94
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Tidskriftsartikel (refereegranskat)abstract
- Bipolar disorder (BD) is a genetically complex mental illness characterized by severe oscillations of mood and behavior. Genome-wide association studies (GWAS) have identified several risk loci that together account for a small portion of the heritability. To identify additional risk loci, we performed a two-stage meta-analysis of >9 million genetic variants in 9,784 bipolar disorder patients and 30,471 controls, the largest GWAS of BD to date. In this study, to increase power we used ∼2,000 lithium-treated cases with a long-term diagnosis of BD from the Consortium on Lithium Genetics, excess controls, and analytic methods optimized for markers on the X-chromosome. In addition to four known loci, results revealed genome-wide significant associations at two novel loci: an intergenic region on 9p21.3 (rs12553324, p=5.87×10(-9); odds ratio=1.12) and markers within ERBB2 (rs2517959, p=4.53×10(-9); odds ratio=1.13). No significant X-chromosome associations were detected and X-linked markers explained very little BD heritability. The results add to a growing list of common autosomal variants involved in BD and illustrate the power of comparing well-characterized cases to an excess of controls in GWAS.
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