| 1. |
- Moayyeri, Alireza, et al.
(författare)
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Genetic determinants of heel bone properties : genome-wide association meta-analysis and replication in the GEFOS/GENOMOS consortium
- 2014
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:11, s. 3054-3068
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Tidskriftsartikel (refereegranskat)abstract
- Quantitative ultrasound of the heel captures heel bone properties that independently predict fracture risk and, with bone mineral density (BMD) assessed by X-ray (DXA), may be convenient alternatives for evaluating osteoporosis and fracture risk. We performed a meta-analysis of genome-wide association (GWA) studies to assess the genetic determinants of heel broadband ultrasound attenuation (BUA; n = 14 260), velocity of sound (VOS; n = 15 514) and BMD (n = 4566) in 13 discovery cohorts. Independent replication involved seven cohorts with GWA data (in silico n = 11 452) and new genotyping in 15 cohorts (de novo n = 24 902). In combined random effects, meta-analysis of the discovery and replication cohorts, nine single nucleotide polymorphisms (SNPs) had genome-wide significant (P < 5 x 10(-8)) associations with heel bone properties. Alongside SNPs within or near previously identified osteoporosis susceptibility genes including ESR1 (6q25.1: rs4869739, rs3020331, rs2982552), SPTBN1 (2p16.2: rs11898505), RSPO3 (6q22.33: rs7741021), WNT16 (7q31.31: rs2908007), DKK1 (10q21.1: rs7902708) and GPATCH1 (19q13.11: rs10416265), we identified a new locus on chromosome 11q14.2 (rs597319 close to TMEM135, a gene recently linked to osteoblastogenesis and longevity) significantly associated with both BUA and VOS (P < 8.23 x 10(-14)). In meta-analyses involving 25 cohorts with up to 14 985 fracture cases, six of 10 SNPs associated with heel bone properties at P < 5 x 10(-6) also had the expected direction of association with any fracture (P < 0.05), including three SNPs with P < 0.005: 6q22.33 (rs7741021), 7q31.31 (rs2908007) and 10q21.1 (rs7902708). In conclusion, this GWA study reveals the effect of several genes common to central DXA-derived BMD and heel ultrasound/DXA measures and points to a new genetic locus with potential implications for better understanding of osteoporosis pathophysiology.
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| 2. |
- Ohlsson, Claes, 1965, et al.
(författare)
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Genetic determinants of serum testosterone concentrations in men.
- 2011
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Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404 .- 1553-7390. ; 7:10
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Tidskriftsartikel (refereegranskat)abstract
- Testosterone concentrations in men are associated with cardiovascular morbidity, osteoporosis, and mortality and are affected by age, smoking, and obesity. Because of serum testosterone's high heritability, we performed a meta-analysis of genome-wide association data in 8,938 men from seven cohorts and followed up the genome-wide significant findings in one in silico (n=871) and two de novo replication cohorts (n=4,620) to identify genetic loci significantly associated with serum testosterone concentration in men. All these loci were also associated with low serum testosterone concentration defined as <300 ng/dl. Two single-nucleotide polymorphisms at the sex hormone-binding globulin (SHBG) locus (17p13-p12) were identified as independently associated with serum testosterone concentration (rs12150660, p=1.2×10(-41) and rs6258, p=2.3×10(-22)). Subjects with ≥ 3 risk alleles of these variants had 6.5-fold higher risk of having low serum testosterone than subjects with no risk allele. The rs5934505 polymorphism near FAM9B on the X chromosome was also associated with testosterone concentrations (p=5.6×10(-16)). The rs6258 polymorphism in exon 4 of SHBG affected SHBG's affinity for binding testosterone and the measured free testosterone fraction (p<0.01). Genetic variants in the SHBG locus and on the X chromosome are associated with a substantial variation in testosterone concentrations and increased risk of low testosterone. rs6258 is the first reported SHBG polymorphism, which affects testosterone binding to SHBG and the free testosterone fraction and could therefore influence the calculation of free testosterone using law-of-mass-action equation.
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| 3. |
- Barrado, David, et al.
(författare)
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15NH3 in the atmosphere of a cool brown dwarf
- 2023
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Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 624:7991, s. 263-266
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Tidskriftsartikel (refereegranskat)abstract
- Brown dwarfs serve as ideal laboratories for studying the atmospheres of giant exoplanets on wide orbits, as the governing physical and chemical processes within them are nearly identical. Understanding the formation of gas-giant planets is challenging, often involving the endeavour to link atmospheric abundance ratios, such as the carbon-to-oxygen (C/O) ratio, to formation scenarios. However, the complexity of planet formation requires further tracers, as the unambiguous interpretation of the measured C/O ratio is fraught with complexity. Isotope ratios, such as deuterium to hydrogen and 14N/15N, offer a promising avenue to gain further insight into this formation process, mirroring their use within the Solar System. For exoplanets, only a handful of constraints on 12C/13C exist, pointing to the accretion of 13C-rich ice from beyond the CO iceline of the disks. Here we report on the mid-infrared detection of the 14NH3 and 15NH3 isotopologues in the atmosphere of a cool brown dwarf with an effective temperature of 380 K in a spectrum taken with the Mid-Infrared Instrument (MIRI) of JWST. As expected, our results reveal a 14N/15N value consistent with star-like formation by gravitational collapse, demonstrating that this ratio can be accurately constrained. Because young stars and their planets should be more strongly enriched in the 15N isotope, we expect that 15NH3 will be detectable in several cold, wide-separation exoplanets.
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| 4. |
- Brown, Sally, et al.
(författare)
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Shifting perspectives on coastal impacts and adaptation
- 2014
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Ingår i: Nature Climate Change. - : Nature Publishing Group. - 1758-678X .- 1758-6798. ; 4:9, s. 752-755
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The Intergovernmental Panel on Climate Change reports reflect evolving attitudes in adapting to sea-level rise by taking a systems approach and recognizing that multiple responses exist to achieve a less hazardous coast.
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| 5. |
- Cannone, Carla, et al.
(författare)
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Addressing Challenges in Long-Term Strategic Energy Planning in LMICs : Learning Pathways in an Energy Planning Ecosystem
- 2023
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Ingår i: Energies. - : MDPI AG. - 1996-1073. ; 16:21
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Tidskriftsartikel (refereegranskat)abstract
- This paper presents an innovative approach to addressing critical global challenges in long-term energy planning for low- and middle-income countries (LMICs). The paper proposes and tests an international enabling environment, a delivery ecosystem, and a community of practice. These components are integrated into workflows that yield four self-sustaining capacity-development outcomes. Planning long-term energy strategies in LMICs is particularly challenging due to limited national agency and poor international coordination. While outsourcing energy planning to foreign experts may appear to be a viable solution, it can lead to a reduction in government agency (the ability of a government to make its own informed analysis and decisions). Additionally, studies commissioned by external experts may have conflicting terms of reference, and a lack of familiarity with local conditions can result in misrepresentations of on-the-ground realities. It is argued here that enhancing national agency and analytical capacity can improve coordination and lead to more robust planning across line ministries and technical assistance (TA) providers. Moreover, the prevailing consulting model hampers the release and accessibility of underlying analytics, making it difficult to retrieve, reuse, and reconstruct consultant outputs. The absence of interoperability among outputs from various consultants hinders the ability to combine and audit the insights they provide. To overcome these challenges, five strategic principles for energy planning in LMICs have been introduced and developed in collaboration with 21 international and research organizations, including the AfDB, IEA, IRENA, IAEA, UNDP, UNECA, the World Bank, and WRI. These principles prioritize national ownership, coherence and inclusivity, capacity, robustness, transparency and accessibility. In this enabling environment, a unique delivery ecosystem consisting of knowledge products and activities is established. The paper focuses on two key knowledge products as examples of this ecosystem: the open-source energy modeling system (OSeMOSYS) and the power system flexibility tool (IRENA FlexTool). These ecosystem elements are designed to meet user-friendliness, retrievability, reusability, reconstructability, repeatability, interoperability, and audibility (U4RIA) goals. To ensure the sustainability of this ecosystem, OpTIMUS is introduced—a community of practice dedicated to maintaining, supporting, expanding, and nurturing the elements within the ecosystem. Among other ecosystem elements, training and research initiatives are introduced, namely the Energy Modelling Platform for Africa, Latin America and the Caribbean, and Asia-Pacific as well as the ICTP Joint Summer School on Modelling Tools for Sustainable Development. Once deployed via workflows, the preliminary outcomes of these capacity-development learning pathways show promise. Further investigation is necessary to evaluate their long-term impacts, scalability, replication, and deployment costs.
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| 6. |
- Dyrek, Achrène, et al.
(författare)
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SO2, silicate clouds, but no CH4 detected in a warm Neptune
- 2024
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Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 625, s. 51-54
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Tidskriftsartikel (refereegranskat)abstract
- WASP-107b is a warm (approximately 740 K) transiting planet with a Neptune-like mass of roughly 30.5 M⊕ and Jupiter-like radius of about 0.94 RJ (refs. 1,2), whose extended atmosphere is eroding3. Previous observations showed evidence for water vapour and a thick, high-altitude condensate layer in the atmosphere of WASP-107b (refs. 4,5). Recently, photochemically produced sulfur dioxide (SO2) was detected in the atmosphere of a hot (about 1,200 K) Saturn-mass planet from transmission spectroscopy near 4.05 μm (refs. 6,7), but for temperatures below about 1,000 K, sulfur is predicted to preferably form sulfur allotropes instead of SO2 (refs. 8,9,10). Here we report the 9σ detection of two fundamental vibration bands of SO2, at 7.35 μm and 8.69 μm, in the transmission spectrum of WASP-107b using the Mid-Infrared Instrument (MIRI) of JWST. This discovery establishes WASP-107b as the second irradiated exoplanet with confirmed photochemistry, extending the temperature range of exoplanets exhibiting detected photochemistry from about 1,200 K down to about 740 K. Furthermore, our spectral analysis reveals the presence of silicate clouds, which are strongly favoured (around 7σ) over simpler cloud set-ups. Furthermore, water is detected (around 12σ) but methane is not. These findings provide evidence of disequilibrium chemistry and indicate a dynamically active atmosphere with a super-solar metallicity.
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| 7. |
- Eriksson, Anna-Lena, 1971, et al.
(författare)
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Genetic Determinants of Circulating Estrogen Levels and Evidence of a Causal Effect of Estradiol on Bone Density in Men.
- 2018
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 103:3, s. 991-1004
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Tidskriftsartikel (refereegranskat)abstract
- Serum estradiol (E2) and estrone (E1) levels exhibit substantial heritability.To investigate the genetic regulation of serum E2 and E1 in men.Genome-wide association study in 11,097 men of European origin from nine epidemiological cohorts.Genetic determinants of serum E2 and E1 levels.Variants in/near CYP19A1 demonstrated the strongest evidence for association with E2, resolving to three independent signals. Two additional independent signals were found on the X chromosome; FAMily with sequence similarity 9, member B (FAM9B), rs5934505 (P = 3.4 × 10-8) and Xq27.3, rs5951794 (P = 3.1 × 10-10). E1 signals were found in CYP19A1 (rs2899472, P = 5.5 × 10-23), in Tripartite motif containing 4 (TRIM4; rs17277546, P = 5.8 × 10-14), and CYP11B1/B2 (rs10093796, P = 1.2 × 10-8). E2 signals in CYP19A1 and FAM9B were associated with bone mineral density (BMD). Mendelian randomization analysis suggested a causal effect of serum E2 on BMD in men. A 1 pg/mL genetically increased E2 was associated with a 0.048 standard deviation increase in lumbar spine BMD (P = 2.8 × 10-12). In men and women combined, CYP19A1 alleles associated with higher E2 levels were associated with lower degrees of insulin resistance.Our findings confirm that CYP19A1 is an important genetic regulator of E2 and E1 levels and strengthen the causal importance of E2 for bone health in men. We also report two independent loci on the X-chromosome for E2, and one locus each in TRIM4 and CYP11B1/B2, for E1.
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| 8. |
- Guccione, Salvatore, et al.
(författare)
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Techno-economic optimisation of a sodium-chloride salt heat exchanger for concentrating solar power applications
- 2022
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Ingår i: Solar Energy. - : Elsevier BV. - 0038-092X .- 1471-1257. ; 239, s. 252-267
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Tidskriftsartikel (refereegranskat)abstract
- To enhance the economic viability of Concentrating solar power (CSP) plant, recent efforts have been directed towards employing high-temperature working fluid in the receiver and incorporating higher-efficiency power cycles. This work presents a techno-economic analysis of a sodium-chloride salt heat exchanger included in a sodium-driven CSP system with a supercritical CO2 power block. A quasi-steady state heat exchanger model was developed based on the TEMA guidelines, with the possibility of being customised in terms of media adopted, constraints, boundary conditions, and heat transfer correlations. The sodium-salt heat exchanger has been designed aiming at minimising the Levelized Cost of Electricity (LCOE) of the plant. The performance and the design of the proposed heat exchanger have been evaluated via multi-objective optimisation and sensitivity analyses. Results show that advanced CSP systems employing sodium and an indirect chloride salt storage can represent an economically viable solution and can drive towards the future goal of 5 USD/MWh. For a base-case 100 MWe plant with 12 h of storage, a LCOE of 72.7 USD/MWh and a capacity factor (CF) higher than 60% were reached. The techno-economic investigations showed the potential LCOE reduction of 6% as well as the flexibility and robustness of the heat exchanger model. The developed tool lays the groundwork to explore potential improvements of this new generation of CSP systems.
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| 9. |
- Huhtaniemi, Ilpo T, et al.
(författare)
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Effect of Polymorphisms in Selected Genes Involved in Pituitary-Testicular Function on Reproductive Hormones and Phenotype in Aging Men.
- 2010
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 95, s. 1898-1908
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Tidskriftsartikel (refereegranskat)abstract
- Context: Polymorphisms in genes involved in regulation, biosynthesis, metabolism, and actions of testicular sex hormones may influence hormone balance and phenotype of aging men. Objective: We investigated the relationships between polymorphisms in genes related to pituitary-testicular endocrine function and health status. Design and Setting: Using cross-sectional baseline data, we conducted a multinational prospective cohort observational study consisting of a population survey of community-dwelling men. Participants: A total of 2748 men, aged 40-79 (mean +/- SD, 60.2 + 11.2) yr, were randomly recruited from eight European centers. Forty-three polymorphisms were genotyped in the following genes: androgen receptor (AR), estrogen receptor-alpha and -beta (ESR1 and ESR2), steroid 5alpha-reductase type II (SRD5A2), 17alpha-hydroxylase/17,20-lyase (CYP17A1), aromatase (CYP19A1), sex hormone-binding globulin (SHBG), LH beta-subunit (LHB), and LH receptor (LHCGR). Main Outcome Measures: We measured the associations between gene polymorphisms and endocrine, metabolic, and phenotypic parameters related to aging and sex hormone action. Results: Several polymorphisms in SHBG, ESR2, AR, CYP19A1, and LHB were significantly associated with circulating levels of SHBG, LH, total, free, and bioavailable testosterone and estradiol, the LH x testosterone product, and indices of insulin sensitivity. Apart from several previously reported associations between genes affecting estrogen levels and heel ultrasound parameters, no associations existed between polymorphisms and nonhormonal variables (anthropometry, blood lipids, blood pressure, hemoglobin, prostate symptoms, prostate-specific antigen, sexual dysfunction, cognition). Conclusion: In aging men, polymorphisms in genes related to the pituitary-testicular endocrine function significantly influence circulating LH, testosterone, and estradiol levels, but the downstream effects may be too small to influence secondary phenotypic parameters.
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| 10. |
- Huhtaniemi, Ilpo T, et al.
(författare)
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Increased Estrogen Rather Than Decreased Androgen Action Is Associated with Longer Androgen Receptor CAG Repeats.
- 2009
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 94, s. 277-284
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Tidskriftsartikel (refereegranskat)abstract
- Context: The individual variability in the waning androgenic-anabolic functions of aging men may be influenced by the CAG repeat polymorphism in exon 1 of the androgen receptor (AR), affecting androgen sensitivity. However, findings on its phenotypic effects are inconclusive. Objective: To investigate the relationships between health status, various reproductive hormones and the AR CAG repeat length. Design: A multi-national prospective cohort observational study - cross-sectional baseline data. Setting: Population survey of community-dwelling men. Participants: Men (40-79-yr-old; n=3,369) randomly recruited from centers in eight European countries; CAG repeat analysis was performed in 2,878 men. Main outcome measures: The correlations of the CAG repeat length with selected endocrine, metabolic and phenotypic parameters related to aging and sex hormone action. Results: Only minor differences were found in CAG repeat lengths between the eight European countries. They showed significant positive association with total, free and bioavailable levels of testosterone (T) and estradiol (E2). FSH but not LH correlated inversely with CAG repeat length. Significant associations were found with bone ultrasound parameters at the calcaneus. Negative correlation was found with triglycerides, but not with other blood lipids, or with anthropometry, blood pressure, hemoglobin, insulin sensitivity, or sexual and prostatic functions. Conclusions: The AR CAG repeat length correlates significantly with serum T and E2 of aging men. Weaker transcriptional activity of the AR with longer CAG-encoded polyglutamine repeats appears to be totally or near-totally compensated for by higher T levels. The residual phenotypic correlations may reflect differences in estrogen levels/actions following aromatization of the higher T levels.
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