| 1. |
- Bar, N., et al.
(författare)
-
A reference map of potential determinants for the human serum metabolome
- 2020
-
Ingår i: Nature. - : Nature Research. - 0028-0836 .- 1476-4687. ; 588:7836, s. 135-140
-
Tidskriftsartikel (refereegranskat)abstract
- The serum metabolome contains a plethora of biomarkers and causative agents of various diseases, some of which are endogenously produced and some that have been taken up from the environment1. The origins of specific compounds are known, including metabolites that are highly heritable2,3, or those that are influenced by the gut microbiome4, by lifestyle choices such as smoking5, or by diet6. However, the key determinants of most metabolites are still poorly understood. Here we measured the levels of 1,251 metabolites in serum samples from a unique and deeply phenotyped healthy human cohort of 491 individuals. We applied machine-learning algorithms to predict metabolite levels in held-out individuals on the basis of host genetics, gut microbiome, clinical parameters, diet, lifestyle and anthropometric measurements, and obtained statistically significant predictions for more than 76% of the profiled metabolites. Diet and microbiome had the strongest predictive power, and each explained hundreds of metabolites—in some cases, explaining more than 50% of the observed variance. We further validated microbiome-related predictions by showing a high replication rate in two geographically independent cohorts7,8 that were not available to us when we trained the algorithms. We used feature attribution analysis9 to reveal specific dietary and bacterial interactions. We further demonstrate that some of these interactions might be causal, as some metabolites that we predicted to be positively associated with bread were found to increase after a randomized clinical trial of bread intervention. Overall, our results reveal potential determinants of more than 800 metabolites, paving the way towards a mechanistic understanding of alterations in metabolites under different conditions and to designing interventions for manipulating the levels of circulating metabolites.
|
|
| 2. |
- Wilman, H. R., et al.
(författare)
-
Genetic studies of abdominal MRI data identify genes regulating hepcidin as major determinants of liver iron concentration
- 2019
-
Ingår i: Journal of Hepatology. - : Elsevier. - 0168-8278 .- 1600-0641. ; 71:3, s. 594-602
-
Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Excess liver iron content is common and is linked to the risk of hepatic and extrahepatic diseases. We aimed to identify genetic variants influencing liver iron content and use genetics to understand its link to other traits and diseases. Methods: First, we performed a genome-wide association study (GWAS) in 8,289 individuals from UK Biobank, whose liver iron level had been quantified by magnetic resonance imaging, before validating our findings in an independent cohort (n = 1,513 from IMI DIRECT). Second, we used Mendelian randomisation to test the causal effects of 25 predominantly metabolic traits on liver iron content. Third, we tested phenome-wide associations between liver iron variants and 770 traits and disease outcomes. Results: We identified 3 independent genetic variants (rs1800562 [C282Y] and rs1799945 [H63D] in HFE and rs855791 [V736A] in TMPRSS6) associated with liver iron content that reached the GWAS significance threshold (p <5 × 10−8). The 2 HFE variants account for ∼85% of all cases of hereditary haemochromatosis. Mendelian randomisation analysis provided evidence that higher central obesity plays a causal role in increased liver iron content. Phenome-wide association analysis demonstrated shared aetiopathogenic mechanisms for elevated liver iron, high blood pressure, cirrhosis, malignancies, neuropsychiatric and rheumatological conditions, while also highlighting inverse associations with anaemias, lipidaemias and ischaemic heart disease. Conclusion: Our study provides genetic evidence that mechanisms underlying higher liver iron content are likely systemic rather than organ specific, that higher central obesity is causally associated with higher liver iron, and that liver iron shares common aetiology with multiple metabolic and non-metabolic diseases. Lay summary: Excess liver iron content is common and is associated with liver diseases and metabolic diseases including diabetes, high blood pressure, and heart disease. We identified 3 genetic variants that are linked to an increased risk of developing higher liver iron content. We show that the same genetic variants are linked to higher risk of many diseases, but they may also be associated with some health advantages. Finally, we use genetic variants associated with waist-to-hip ratio as a tool to show that central obesity is causally associated with increased liver iron content.
|
|
| 3. |
- Azimoh, C. L., et al.
(författare)
-
Replicability and scalability of mini-grid solution to rural electrification programs in sub-Saharan Africa
- 2017
-
Ingår i: Renewable Energy. - : Elsevier BV. - 0960-1481. ; 106, s. 222-231
-
Tidskriftsartikel (refereegranskat)abstract
- The assessment of off-grid electrification programs in developing countries largely based on mini-grid and solar home system (SHS) has shown that they are faced with low development imparts and sustainability challenges, which has resulted in failure of many projects. This study provides solutions on how to surmount these challenges, leaning on the experience of a hybrid solar-diesel mini-grid at Tsumkwe village in Namibia. It provides analyses of a case study based on empirical evidence from field studies, interviews of representatives of households, public institutions and energy providers. In addition, it investigates the technical challenges and economic impacts of the electrification program. HOMER™ and MATLAB™ models were used in the analysis and investigations. The findings show that despite the challenges, the system has been sustained because it keyed into an existing structure with growth potentials. The progressive tariff system adopted by the government helped to cushion costs and allow low income households in the energy matrix. Adoption of strict maintenance measures, and implementation of energy efficiency measures prior to the commissioning of the program, resulted in the reduction of costs. The success elements identified in this study could be extrapolated in other sub-Saharan African countries if the challenges are properly addressed.
|
|
| 4. |
|
|
| 5. |
- Butorin, Sergei, et al.
(författare)
-
Effect of Ag Doping on Electronic Structure of Cluster Compounds AgxMo9Se11 (x = 3.4, 3.9)
- 2018
-
Ingår i: ACS Applied Energy Materials. - : American Chemical Society (ACS). - 2574-0962. ; 1:8, s. 4032-4039
-
Tidskriftsartikel (refereegranskat)abstract
- The electronic structure of AgxMo9Se11 as a potential material for thermoelectric applications was studied using high-energy-resolution fluorescence-detection X-ray absorption spectroscopy (HERFD-XAS) and the resonant inelastic X-ray scattering (RIXS) technique. The experiments were supported by first-principle calculations using density functional theory (DFT). The analysis of obtained spectra indicate the presence of subvalent (less than 1+) Ag in AgxMo9Se11. The advanced HERFD-XAS measurements allowed us to resolve the contribution of the electronic states at the Fermi level of AgxMo9Se11 and to monitor its dependence on the x value. A comparison of the experimental data with the results of the DFT calculations suggests the importance of the Ag2-type sites with the shortest Ag–Se distance for affecting the properties of AgxMo9Se11.
|
|
| 6. |
- de Almeida, J. S., et al.
(författare)
-
On the dynamical stability and metallic behavior of YH3 under pressure
- 2009
-
Ingår i: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 94:25, s. 251913-
-
Tidskriftsartikel (refereegranskat)abstract
- Wereport on the behavior of structural and electronic properties ofyttrium trihydride under pressure using first principles calculations. We showthat YH3 undergoes a structural transformation and its high pressurephase is dynamically stable under pressure since the peak atthe imaginary frequencies of the phonon density of states, whichaccount for the structural instability disappears at high pressure. Additionally,our GW calculations indicate a metallization of the high pressurecubic phase of YH3.
|
|
| 7. |
- Finizia, Caterina, 1961, et al.
(författare)
-
Advanced laryngeal cancer T3-T4 in Sweden: a retrospective study 1986-1990. Survival and locoregional control related to treatment.
- 1996
-
Ingår i: Acta oto-laryngologica. - : Informa UK Limited. - 0001-6489 .- 1651-2251. ; 116:6, s. 906-12
-
Tidskriftsartikel (refereegranskat)abstract
- Different treatment modalities for advanced laryngeal cancer are much discussed in the literature. One-hundred-and-sixty patients with T3-4, N0-3, M0-1 laryngeal cancer diagnosed in Sweden between 1986 and 1990 were retrospectively analysed. One hundred (65 T3: 35 T4) received radical radiotherapy with salvage surgery (RRSS) in case of residual or recurrent disease. Thirty-eight (11T3: 27 T4) patients received surgery with or without radiotherapy (S +/- RT). Twenty-two patients received no treatment. After a median follow up of 4.4 years, the estimated 5-year actuarial corrected survival and 3-year locoregional control were 59% and 44% for T3 RRSS and 47% and 54% for T3 S +/- RT. No significant difference between the different treatment modalities was found. The 5-year corrected survival rate and the locoregional control at 3 years between T4-RRSS (32%; 26%) and T4-S + RT (58%; 68%) groups were significantly different (p < 0.05 and p < 0.01). This might suggest that surgery with or without radiotherapy still has its place as a treatment modality for patients with advanced T4 laryngeal carcinoma.
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
- Klintenberg, Mattias, et al.
(författare)
-
Evolving properties of two-dimensional materials : from graphene to graphite
- 2009
-
Ingår i: Journal of Physics. - : IOP Publishing. - 0953-8984 .- 1361-648X. ; 21:33, s. 335502-
-
Tidskriftsartikel (refereegranskat)abstract
- We have studied theoretically, using density functional theory, several material properties when going from one C layer in graphene to two and three graphene layers and on to graphite. The properties we have focused on are the elastic constants, electronic structure (energy bands and density of states), and the dielectric properties. For any of the properties we have investigated the modification due to an increase in the number of graphene layers is within a few per cent. Our results are in agreement with the analysis presented recently by Kopelevich and Esquinazi (unpublished).
|
|
