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Träfflista för sökning "WFRF:(Jensen Torben R.) "

Sökning: WFRF:(Jensen Torben R.)

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1.
  • Turcot, Valerie, et al. (författare)
  • Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity
  • 2018
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:1, s. 26-41
  • 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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2.
  • Marouli, Eirini, et al. (författare)
  • Rare and low-frequency coding variants alter human adult height
  • 2017
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 542:7640, s. 186-190
  • 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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3.
  • Kanoni, Stavroula, et al. (författare)
  • Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
  • 2022
  • Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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4.
  • Mahajan, Anubha, et al. (författare)
  • Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation
  • 2022
  • Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 54:5, s. 560-572
  • Tidskriftsartikel (refereegranskat)abstract
    • We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 x 10(-9)), which were delineated to 338 distinct association signals. Fine-mapping of these signals was enhanced by the increased sample size and expanded population diversity of the multi-ancestry meta-analysis, which localized 54.4% of T2D associations to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying the foundations for functional investigations. Multi-ancestry genetic risk scores enhanced transferability of T2D prediction across diverse populations. Our study provides a step toward more effective clinical translation of T2D GWAS to improve global health for all, irrespective of genetic background. Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.
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5.
  • Mahajan, Anubha, et al. (författare)
  • Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes
  • 2018
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:4, s. 559-571
  • 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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6.
  • Manning, Alisa, et al. (författare)
  • A Low-Frequency Inactivating AKT2 Variant Enriched in the Finnish Population Is Associated With Fasting Insulin Levels and Type 2 Diabetes Risk
  • 2017
  • Ingår i: Diabetes. - : AMER DIABETES ASSOC. - 0012-1797 .- 1939-327X. ; 66:7, s. 2019-2032
  • 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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7.
  • Flannick, Jason, et al. (författare)
  • Data Descriptor : Sequence data and association statistics from 12,940 type 2 diabetes cases and controls
  • 2017
  • Ingår i: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 4
  • Tidskriftsartikel (refereegranskat)abstract
    • To investigate the genetic basis of type 2 diabetes (T2D) to high resolution, the GoT2D and T2D-GENES consortia catalogued variation from whole-genome sequencing of 2,657 European individuals and exome sequencing of 12,940 individuals of multiple ancestries. Over 27M SNPs, indels, and structural variants were identified, including 99% of low-frequency (minor allele frequency [MAF] 0.1-5%) non-coding variants in the whole-genome sequenced individuals and 99.7% of low-frequency coding variants in the whole-exome sequenced individuals. Each variant was tested for association with T2D in the sequenced individuals, and, to increase power, most were tested in larger numbers of individuals (> 80% of low-frequency coding variants in similar to ~82 K Europeans via the exome chip, and similar to ~90% of low-frequency non-coding variants in similar to ~44 K Europeans via genotype imputation). The variants, genotypes, and association statistics from these analyses provide the largest reference to date of human genetic information relevant to T2D, for use in activities such as T2D-focused genotype imputation, functional characterization of variants or genes, and other novel analyses to detect associations between sequence variation and T2D.
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8.
  • Fuchsberger, Christian, et al. (författare)
  • The genetic architecture of type 2 diabetes
  • 2016
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 536:7614, s. 41-47
  • Tidskriftsartikel (refereegranskat)abstract
    • The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of the heritability of this disease. Here, to test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole-genome sequencing in 2,657 European individuals with and without diabetes, and exome sequencing in 12,940 individuals from five ancestry groups. To increase statistical power, we expanded the sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support the idea that lower-frequency variants have a major role in predisposition to type 2 diabetes.
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9.
  • Justice, Anne E., et al. (författare)
  • Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution
  • 2019
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:3, s. 452-469
  • 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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10.
  • Surendran, Praveen, et al. (författare)
  • Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals
  • 2020
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 52:12, s. 1314-1332
  • Tidskriftsartikel (refereegranskat)abstract
    • Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to similar to 1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency <= 0.01) variant BP associations (P < 5 x 10(-8)), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were similar to 8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare-variant analyses for identifying candidate genes and the results highlight potential therapeutic targets.
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11.
  • Wormser, David, et al. (författare)
  • Adult height and the risk of cause-specific death and vascular morbidity in 1 million people : individual participant meta-analysis
  • 2012
  • Ingår i: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 41:5, s. 1419-1433
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundThe extent to which adult height, a biomarker of the interplay of genetic endowment and early-life experiences, is related to risk of chronic diseases in adulthood is uncertain.MethodsWe calculated hazard ratios (HRs) for height, assessed in increments of 6.5 cm, using individual-participant data on 174 374 deaths or major non-fatal vascular outcomes recorded among 1 085 949 people in 121 prospective studies.ResultsFor people born between 1900 and 1960, mean adult height increased 0.5-1 cm with each successive decade of birth. After adjustment for age, sex, smoking and year of birth, HRs per 6.5 cm greater height were 0.97 (95% confidence interval: 0.96-0.99) for death from any cause, 0.94 (0.93-0.96) for death from vascular causes, 1.04 (1.03-1.06) for death from cancer and 0.92 (0.90-0.94) for death from other causes. Height was negatively associated with death from coronary disease, stroke subtypes, heart failure, stomach and oral cancers, chronic obstructive pulmonary disease, mental disorders, liver disease and external causes. In contrast, height was positively associated with death from ruptured aortic aneurysm, pulmonary embolism, melanoma and cancers of the pancreas, endocrine and nervous systems, ovary, breast, prostate, colorectum, blood and lung. HRs per 6.5 cm greater height ranged from 1.26 (1.12-1.42) for risk of melanoma death to 0.84 (0.80-0.89) for risk of death from chronic obstructive pulmonary disease. HRs were not appreciably altered after further adjustment for adiposity, blood pressure, lipids, inflammation biomarkers, diabetes mellitus, alcohol consumption or socio-economic indicators.ConclusionAdult height has directionally opposing relationships with risk of death from several different major causes of chronic diseases.
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12.
  • Kraja, Aldi T., et al. (författare)
  • New Blood Pressure-Associated Loci Identified in Meta-Analyses of 475000 Individuals
  • 2017
  • Ingår i: Circulation. - : LIPPINCOTT WILLIAMS & WILKINS. - 1942-325X .- 1942-3268. ; 10:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Background - Genome-wide association studies have recently identified >400 loci that harbor DNA sequence variants that influence blood pressure (BP). Our earlier studies identified and validated 56 single nucleotide variants (SNVs) associated with BP from meta-analyses of exome chip genotype data. An additional 100 variants yielded suggestive evidence of association.Methods and Results - Here, we augment the sample with 140886 European individuals from the UK Biobank, in whom 77 of the 100 suggestive SNVs were available for association analysis with systolic BP or diastolic BP or pulse pressure. We performed 2 meta-analyses, one in individuals of European, South Asian, African, and Hispanic descent (pan-ancestry, approximate to 475000), and the other in the subset of individuals of European descent (approximate to 423000). Twenty-one SNVs were genome-wide significant (P<5x10(-8) ) for BP, of which 4 are new BP loci: rs9678851 (missense, SLC4A1AP), rs7437940 (AFAP1), rs13303 (missense, STAB1), and rs1055144 (7p15.2). In addition, we identified a potentially independent novel BP-associated SNV, rs3416322 (missense, SYNPO2L) at a known locus, uncorrelated with the previously reported SNVs. Two SNVs are associated with expression levels of nearby genes, and SNVs at 3 loci are associated with other traits. One SNV with a minor allele frequency <0.01, (rs3025380 at DBH) was genome-wide significant.Conclusions - We report 4 novel loci associated with BP regulation, and 1 independent variant at an established BP locus. This analysis highlights several candidate genes with variation that alter protein function or gene expression for potential follow-up.
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13.
  • Mahajan, Anubha, et al. (författare)
  • Fine-mapping type 2 diabetes loci to single-variant resolution using high-density imputation and islet-specific epigenome maps
  • 2018
  • Ingår i: Nature Genetics. - : NATURE PUBLISHING GROUP. - 1061-4036 .- 1546-1718. ; 50:11, s. 1505-
  • Tidskriftsartikel (refereegranskat)abstract
    • We expanded GWAS discovery for type 2 diabetes (T2D) by combining data from 898,130 European-descent individuals (9% cases), after imputation to high-density reference panels. With these data, we (i) extend the inventory of T2D-risk variants (243 loci,135 newly implicated in T2D predisposition, comprising 403 distinct association signals); (ii) enrich discovery of lower-frequency risk alleles (80 index variants with minor allele frequency <5%,14 with estimated allelic odds ratio >2); (iii) substantially improve fine-mapping of causal variants (at 51 signals, one variant accounted for >80% posterior probability of association (PPA)); (iv) extend fine-mapping through integration of tissue-specific epigenomic information (islet regulatory annotations extend the number of variants with PPA >80% to 73); (v) highlight validated therapeutic targets (18 genes with associations attributable to coding variants); and (vi) demonstrate enhanced potential for clinical translation (genome-wide chip heritability explains 18% of T2D risk; individuals in the extremes of a T2D polygenic risk score differ more than ninefold in prevalence).
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14.
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15.
  • Surendran, Praveen, et al. (författare)
  • Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension
  • 2016
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 48:10, s. 1151-1161
  • Tidskriftsartikel (refereegranskat)abstract
    • High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low-frequency and common genetic variants in up to 192,763 individuals and used -1/4155,063 samples for independent replication. We identified 30 new blood pressure- or hypertension-associated genetic regions in the general population, including 3 rare missense variants in RBM47, COL21A1 and RRAS with larger effects (>1.5 mm Hg/allele) than common variants. Multiple rare nonsense and missense variant associations were found in A2ML1, and a low-frequency nonsense variant in ENPEP was identified. Our data extend the spectrum of allelic variation underlying blood pressure traits and hypertension, provide new insights into the pathophysiology of hypertension and indicate new targets for clinical intervention.
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16.
  • Chami, Nathalie, et al. (författare)
  • Exome Genotyping Identifies Pleiotropic Variants Associated with Red Blood Cell Traits
  • 2016
  • Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 99:1, s. 8-21
  • Tidskriftsartikel (refereegranskat)abstract
    • Red blood cell (RBC) traits are important heritable clinical biomarkers and modifiers of disease severity. To identify coding genetic variants associated with these traits, we conducted meta-analyses of seven RBC phenotypes in 130,273 multi-ethnic individuals from studies genotyped on an exome array. After conditional analyses and replication in 27,480 independent individuals, we identified 16 new RBC variants. We found low-frequency missense variants in MAP1A (rs55707100, minor allele frequency [MAF] = 3.3%, p = 2 x 10(-10) for hemoglobin [HGB]) and HNF4A (rs1800961, MAF = 2.4%, p < 3 x 10(-8) for hematocrit [HCT] and HGB). In African Americans, we identified a nonsense variant in CD36 associated with higher RBC distribution width (rs3211938, MAF = 8.7%, p = 7 x 10(-11)) and showed that it is associated with lower CD36 expression and strong allelic imbalance in ex vivo differentiated human erythroblasts. We also identified a rare missense variant in ALAS2 (rs201062903, MAF = 0.2%) associated with lower mean corpuscular volume and mean corpuscular hemoglobin (p < 8 x 10(-9)). Mendelian mutations in ALAS2 are a cause of sideroblastic anemia and erythropoietic protoporphyria. Gene-based testing highlighted three rare missense variants in PKLR, a gene mutated in Mendelian non-spherocytic hemolytic anemia, associated with HGB and HCT (SKAT p < 8 x 10(-7)). These rare, low-frequency, and common RBC variants showed pleiotropy, being also associated with platelet, white blood cell, and lipid traits. Our association results and functional annotation suggest the involvement of new genes in human erythropoiesis. We also confirm that rare and low-frequency variants play a role in the architecture of complex human traits, although their phenotypic effect is generally smaller than originally anticipated.
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17.
  • Pennells, Lisa, et al. (författare)
  • Equalization of four cardiovascular risk algorithms after systematic recalibration : individual-participant meta-analysis of 86 prospective studies
  • 2019
  • Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 40:7, s. 621-
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: There is debate about the optimum algorithm for cardiovascular disease (CVD) risk estimation. We conducted head-to-head comparisons of four algorithms recommended by primary prevention guidelines, before and after ‘recalibration’, a method that adapts risk algorithms to take account of differences in the risk characteristics of the populations being studied.Methods and results: Using individual-participant data on 360 737 participants without CVD at baseline in 86 prospective studies from 22 countries, we compared the Framingham risk score (FRS), Systematic COronary Risk Evaluation (SCORE), pooled cohort equations (PCE), and Reynolds risk score (RRS). We calculated measures of risk discrimination and calibration, and modelled clinical implications of initiating statin therapy in people judged to be at ‘high’ 10 year CVD risk. Original risk algorithms were recalibrated using the risk factor profile and CVD incidence of target populations. The four algorithms had similar risk discrimination. Before recalibration, FRS, SCORE, and PCE over-predicted CVD risk on average by 10%, 52%, and 41%, respectively, whereas RRS under-predicted by 10%. Original versions of algorithms classified 29–39% of individuals aged ≥40 years as high risk. By contrast, recalibration reduced this proportion to 22–24% for every algorithm. We estimated that to prevent one CVD event, it would be necessary to initiate statin therapy in 44–51 such individuals using original algorithms, in contrast to 37–39 individuals with recalibrated algorithms.Conclusion: Before recalibration, the clinical performance of four widely used CVD risk algorithms varied substantially. By contrast, simple recalibration nearly equalized their performance and improved modelled targeting of preventive action to clinical need.
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18.
  • Grinderslev, Jakob B., et al. (författare)
  • Polymorphism and solid solutions of trimethylammonium monocarboranes
  • 2022
  • Ingår i: Dalton Transactions. - : Royal Society of Chemistry (RSC). - 1477-9226 .- 1477-9234. ; 51:41, s. 15806-15815
  • Tidskriftsartikel (refereegranskat)abstract
    • Metal closo-boranes have recently received significant attention as solid-state electrolytes due to their high thermal and electrochemical stability, and the weak interaction between the cat- and anion, facilitating fast ionic conductivity. Here we report a synthesis method for obtaining a novel mixed closo-carborane compound, [NH(CH3)3][(CB8H9)0.26(CB9H10)0.66(CB11H12)0.08]. The crystal structures are investigated for [NH(CH3)3][CB9H10] and [NH(CH3)3][(CB8H9)0.26(CB9H10)0.66(CB11H12)0.08], revealing that the latter forms a solid solution isostructural to [NH(CH3)3][CB9H10]. The compounds exhibit polymorphism as a function of temperature, and we report the discovery of four polymorphs of [NH(CH3)3][CB9H10] and four isostructural solid solution [NH(CH3)3][(CB8H9)0.26(CB9H10)0.66(CB11H12)0.08], along with a high-temperature decomposition intermediate of the latter. The α-polymorph is an ordered structure, with increasing amounts of disorder for the β- and γ-polymorphs, while the high temperature δ- and ϵ-polymorphs at T > 476 K are fully disordered on both the cation and anion site. These new compounds may be used as precursors for new types of solid-state ionic conductors.
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19.
  • Mahajan, Anubha, et al. (författare)
  • Identification and Functional Characterization of G6PC2 Coding Variants Influencing Glycemic Traits Define an Effector Transcript at the G6PC2-ABCB11 Locus.
  • 2015
  • Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404 .- 1553-7390. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome wide association studies (GWAS) for fasting glucose (FG) and insulin (FI) have identified common variant signals which explain 4.8% and 1.2% of trait variance, respectively. It is hypothesized that low-frequency and rare variants could contribute substantially to unexplained genetic variance. To test this, we analyzed exome-array data from up to 33,231 non-diabetic individuals of European ancestry. We found exome-wide significant (P<5×10-7) evidence for two loci not previously highlighted by common variant GWAS: GLP1R (p.Ala316Thr, minor allele frequency (MAF)=1.5%) influencing FG levels, and URB2 (p.Glu594Val, MAF = 0.1%) influencing FI levels. Coding variant associations can highlight potential effector genes at (non-coding) GWAS signals. At the G6PC2/ABCB11 locus, we identified multiple coding variants in G6PC2 (p.Val219Leu, p.His177Tyr, and p.Tyr207Ser) influencing FG levels, conditionally independent of each other and the non-coding GWAS signal. In vitro assays demonstrate that these associated coding alleles result in reduced protein abundance via proteasomal degradation, establishing G6PC2 as an effector gene at this locus. Reconciliation of single-variant associations and functional effects was only possible when haplotype phase was considered. In contrast to earlier reports suggesting that, paradoxically, glucose-raising alleles at this locus are protective against type 2 diabetes (T2D), the p.Val219Leu G6PC2 variant displayed a modest but directionally consistent association with T2D risk. Coding variant associations for glycemic traits in GWAS signals highlight PCSK1, RREB1, and ZHX3 as likely effector transcripts. These coding variant association signals do not have a major impact on the trait variance explained, but they do provide valuable biological insights.
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20.
  • Qi, Qibin, et al. (författare)
  • FTO genetic variants, dietary intake and body mass index : insights from 177 330 individuals
  • 2014
  • Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:25, s. 6961-6972
  • Tidskriftsartikel (refereegranskat)abstract
    • FTO is the strongest known genetic susceptibility locus for obesity. Experimental studies in animals suggest the potential roles of FTO in regulating food intake. The interactive relation among FTO variants, dietary intake and body mass index (BMI) is complex and results from previous often small-scale studies in humans are highly inconsistent. We performed large-scale analyses based on data from 177 330 adults (154 439 Whites, 5776 African Americans and 17 115 Asians) from 40 studies to examine: (i) the association between the FTO-rs9939609 variant (or a proxy single-nucleotide polymorphism) and total energy and macronutrient intake and (ii) the interaction between the FTO variant and dietary intake on BMI. The minor allele (A-allele) of the FTO-rs9939609 variant was associated with higher BMI in Whites (effect per allele = 0.34 [0.31, 0.37] kg/m(2), P = 1.9 × 10(-105)), and all participants (0.30 [0.30, 0.35] kg/m(2), P = 3.6 × 10(-107)). The BMI-increasing allele of the FTO variant showed a significant association with higher dietary protein intake (effect per allele = 0.08 [0.06, 0.10] %, P = 2.4 × 10(-16)), and relative weak associations with lower total energy intake (-6.4 [-10.1, -2.6] kcal/day, P = 0.001) and lower dietary carbohydrate intake (-0.07 [-0.11, -0.02] %, P = 0.004). The associations with protein (P = 7.5 × 10(-9)) and total energy (P = 0.002) were attenuated but remained significant after adjustment for BMI. We did not find significant interactions between the FTO variant and dietary intake of total energy, protein, carbohydrate or fat on BMI. Our findings suggest a positive association between the BMI-increasing allele of FTO variant and higher dietary protein intake and offer insight into potential link between FTO, dietary protein intake and adiposity.
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21.
  • Wessel, Jennifer, et al. (författare)
  • Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility
  • 2015
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6
  • 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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22.
  • Callini, Elsa, et al. (författare)
  • Complex and liquid hydrides for energy storage
  • 2016
  • Ingår i: Applied Physics A. - : Springer Science and Business Media LLC. - 0947-8396 .- 1432-0630. ; 122:4
  • Tidskriftsartikel (refereegranskat)abstract
    • The research on complex hydrides for hydrogen storage was initiated by the discovery of Ti as a hydrogen sorption catalyst in NaAlH4 by Boris Bogdanovic in 1996. A large number of new complex hydride materials in various forms and combinations have been synthesized and characterized, and the knowledge regarding the properties of complex hydrides and the synthesis methods has grown enormously since then. A significant portion of the research groups active in the field of complex hydrides is collaborators in the International Energy Agreement Task 32. This paper reports about the important issues in the field of complex hydride research, i.e. the synthesis of borohydrides, the thermodynamics of complex hydrides, the effects of size and confinement, the hydrogen sorption mechanism and the complex hydride composites as well as the properties of liquid complex hydrides. This paper is the result of the collaboration of several groups and is an excellent summary of the recent achievements.
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23.
  • Callini, Elsa, et al. (författare)
  • Nanostructured materials for solid-state hydrogen storage : A review of the achievement of COST Action MP1103
  • 2016
  • Ingår i: International journal of hydrogen energy. - : Elsevier. - 0360-3199 .- 1879-3487. ; 41:32, s. 14404-14428
  • Tidskriftsartikel (refereegranskat)abstract
    • In the framework of the European Cooperation in Science and Technology (COST) Action MP1103 Nanostructured Materials for Solid-State Hydrogen Storage were synthesized, characterized and modeled. This Action dealt with the state of the art of energy storage and set up a competitive and coordinated network capable to define new and unexplored ways for Solid State Hydrogen Storage by innovative and interdisciplinary research within the European Research Area. An important number of new compounds have been synthesized: metal hydrides, complex hydrides, metal halide ammines and amidoboranes. Tuning the structure from bulk to thin film, nanoparticles and nanoconfined composites improved the hydrogen sorption properties and opened the perspective to new technological applications. Direct imaging of the hydrogenation reactions and in situ measurements under operando conditions have been carried out in these studies. Computational screening methods allowed the prediction of suitable compounds for hydrogen storage and the modeling of the hydrogen sorption reactions on mono-, bi-, and three-dimensional systems. This manuscript presents a review of the main achievements of this Action.
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24.
  • Cerny, Radovan, et al. (författare)
  • NaSc(BH4)(4): A Novel Scandium-Based Borohydride
  • 2010
  • Ingår i: Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 114:2, s. 1357-1364
  • Tidskriftsartikel (refereegranskat)abstract
    • A new alkaline transition-metal borohydride, NaSc(BH4)(4), is presented. The compound has been studied using a combination of in situ synchrotron radiation powder X-ray diffraction, thermal analysis, and vibrational and NMR spectroscopy. NaSc(BH4)(4) forms at ambient conditions in ball-milled mixtures of sodium borohydride and ScCl3. A new tertiary chloride Na3ScCl6 (P2(1)/n, a = 6.7375(3) angstrom, b = 7.1567(3) angstrom, c = 9,9316(5) angstrom, beta = 90.491(3)degrees, V = 478.87(4) angstrom(3)), isostructural to Na3TiCl6, was identified as an additional phase in all samples. This indicates that the formation of NaSc(BH4)(4) differs from a simple metathesis reaction, and the highest scandium borohydride yield (22 wt %) was obtained with a reactant ratio of ScCl3/NaBH4 of 1:2. NaSc(BH4)(4) crystallizes in the orthorhombic crystal system with the space group symmetry Cmcm (a = 8.170(2) angstrom, b = 11.875(3) angstrom, c = 9.018(2) angstrom, V = 874.9(3) angstrom(3)). The Structure of NaSc(BH4)(4) consists of isolated homoleptic scandium tetraborohydride anions, [Sc(BH4)(4)](-), located inside slightly distorted trigonal Na-6 prisms (each second prism is empty, triangular angles of 55.5 and 69.1 degrees). The experimental results show that each Sc3+ is tetrahedrally Surrounded by four BH4 tetrahedra with a 12-fold coordination of H to Sc, while Na+ is surrounded by six BH4 tetrahedra in a quite regular octahedral coordination with a (6 + 12)-fold coordination of H to Na. The packing of Na+ cations and [Sc(BH)(4))(4)](-) anions in NaSc(BH4)(4) is a deformation variant of the hexagonal NiAs structure type. NaSc(BH4)(4) is stable from RT up to similar to 410 K, Where the compound melts and then releases hydrogen in two rapidly occurring steps between 440 and 490 K and 495 and 540 K. Thermal expansion of NaSc(BH4)(4) between RT and 408 K is anisotropic, and lattice parameter b shows strong anomaly close to the melting temperature.
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25.
  • Cerny, Radovan, et al. (författare)
  • Structure and Characterization of KSc(BH4)(4)
  • 2010
  • Ingår i: Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 114:45, s. 19540-19549
  • Tidskriftsartikel (refereegranskat)abstract
    • A new potassium scandium borohydride, KSc(BH4)(4), is presented and characterized by a combination of in situ synchrotron radiation powder X-ray diffraction, thermal analysis, and vibrational and NMR spectroscopy. The title compound, KSc(BH4)(4), forms at ambient conditions in ball milled mixtures of potassium borohydride and ScCl3 together with a new ternary chloride K3ScCl6, which is also structurally characterized. This indicates that the formation of KSc(BH4)(4) differs from a simple metathesis reaction, and the highest scandium borohydride yield (similar to 31 mol %) can be obtained with a reactant ratio KBH4:ScCl3 of 2:1. KSc(BH4)(4) crystallizes in the orthorhombic crystal system, a = 11.856(5), b = 7.800(3), c = 10.126(6) angstrom, v = 936.4(8) angstrom(3) at RT, with the space group symmetry Prima. KSc(BH4)(4) has a BaSO4 type structure where the BH4 tetrahedra take the oxygen positions. Regarding the packing of cations, K+, and complex anions, [Sc(BH4)(4)](-), the structure of KSc(BH4)(4) can be seen as a distorted variant of orthorhombic neptunium, Np, metal. Thermal expansion of KSc(BH4)(4) in the temperature range RT to 405 K is anisotropic, and the lattice parameter b shows strong nonlinearity upon approaching the melting temperature. The vibrational and NMR spectra are consistent with the structural model, and previous investigations of the related compounds ASc(BH4)(4) with A = Li, Na. KSc(BH4)(4) is stable from RT up to similar to 405 K, where the compound melts and then releases hydrogen in two rapid steps approximately at 460-500 K and 510-590 K. The hydrogen release involves the formation of KBH4, which reacts with K3ScCl6 and forms a solid solution, K(BH4)(1-x)Cl-x. The ternary potassium scandium chloride K3ScCl6 observed in all samples has a monoclinic structure at room temperature, P2(1)/a, a = 12.729(3), b = 7.367(2), c = 12.825(3) angstrom, beta = 109.22(2)degrees, V = 1135.6(4) angstrom(3), which is isostructural to K3MoCl6. The monoclinic polymorph transforms to cubic at 635 K, a = 10.694 angstrom (based on diffraction data measured at 769 K), which is isostructural to the high temperature phase of K3YCl6.
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26.
  • Hansen, Bjarne R. S., et al. (författare)
  • Hydrogen Storage Capacity Loss in a LiBH4-Al Composite
  • 2013
  • Ingår i: Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 117:15, s. 7423-7432
  • Tidskriftsartikel (refereegranskat)abstract
    • A detailed investigation of the decomposition reactions and decay in the hydrogen storage capacity during repeated hydrogen release and uptake cycles for the reactive composite LiBH4-Al (2:3) is presented. Furthermore, the influence of a titanium boride, TiB2, additive is investigated. The study combines information from multiple techniques: in situ synchrotron radiation powder X-ray diffraction, Sieverts measurements, simultaneous thermogravimetric analysis, differential scanning calorimetry and mass spectroscopy, solid-state magic-angle spinning nuclear magnetic resonance (MAS NMR), and Raman spectroscopy. The decomposition of LiBH4-Al results in the formation of LiAl, AlB2, and Li2B12H12 via several reactions and intermediate compounds. The TiB2 additive appears to have a limited effect on the decomposition pathway of the samples, but seems to facilitate formation of intermediate species at lower temperatures compared to the sample without additive. Solid solutions of LixAl1-xB2 or Al1-xB2 are observed during decomposition and from Rietveld refinement the composition of the solid solution is estimated to be Li0.22Al0.78B2. The intercalation of Li in the AlB2 structure is further investigated by B-11 and Al-27 MAS NMR spectra of the LiH-AlB2 and AlB2 samples (presented in Supporting Information). Hydrogen release and uptake for LiBH4-Al reveals a significant loss in the hydrogen storage capacity, that is, after four cycles a capacity of about 45% remains, and after 10 cycles, the capacity is degraded to approximately 15% of the theoretically available hydrogen content. This capacity loss may be due to the formation of Li2B12H12, as observed by B-11 MAS NMR and Raman spectroscopy. Formation of Li2B12H12 has previously been observed during the decomposition of LiBH4, but it has not been reported earlier in the LiBH4-Al (2:3) system.
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27.
  • Jackson, Victoria E, et al. (författare)
  • Meta-analysis of exome array data identifies six novel genetic loci for lung function.
  • 2018
  • Ingår i: Wellcome open research. - : F1000 Research Ltd. - 2398-502X. ; 3
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Over 90 regions of the genome have been associated with lung function to date, many of which have also been implicated in chronic obstructive pulmonary disease. Methods: We carried out meta-analyses of exome array data and three lung function measures: forced expiratory volume in one second (FEV 1), forced vital capacity (FVC) and the ratio of FEV 1 to FVC (FEV 1/FVC). These analyses by the SpiroMeta and CHARGE consortia included 60,749 individuals of European ancestry from 23 studies, and 7,721 individuals of African Ancestry from 5 studies in the discovery stage, with follow-up in up to 111,556 independent individuals. Results: We identified significant (P<2·8x10 -7) associations with six SNPs: a nonsynonymous variant in RPAP1, which is predicted to be damaging, three intronic SNPs ( SEC24C, CASC17 and UQCC1) and two intergenic SNPs near to LY86 and FGF10. Expression quantitative trait loci analyses found evidence for regulation of gene expression at three signals and implicated several genes, including TYRO3 and PLAU. Conclusions: Further interrogation of these loci could provide greater understanding of the determinants of lung function and pulmonary disease.
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28.
  • Minella, Christian Bonatto, et al. (författare)
  • Effect of Transition Metal Fluorides on the Sorption Properties and Reversible Formation of Ca(BH4)(2)
  • 2011
  • Ingår i: Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 115:5, s. 2497-2504
  • Tidskriftsartikel (refereegranskat)abstract
    • Light metal borohydrides are considered as promising materials for solid state hydrogen storage. Because of the high hydrogen content of 11.5 wt % and the rather low dehydrogenation enthalpy of 32 kJ mol(-1)H(2), Ca(BH4)(2) is considered to be one of the most interesting compounds in this class of materials. In the present work, the effect of selected TM-fluoride (TM = transition metal) additives on the reversible formation of Ca(BH4)(2) was investigated by means of thermovolumetric, calorimetric, Fourier transform infrared spectroscopy, and ex situ, and in situ synchrotron radiation powder X-ray diffraction (SR-PXD) measurements. Furthermore, selected desorbed samples were analyzed by B-11{H-1} solid state magic angle spinning nuclear magnetic resonance (MAS NMR). Under the conditions used in this study (145 bar H-2 pressure and 350 degrees C), TiF4 and NbF5 were the only additives causing partial reversibility. In these two cases, B-11{H-1} MAS NMR analyses detected CaB6 and likely CaB12H12 in the dehydrogenation products. Elemental boron was found in the decomposition products of Ca(BH4)(2) samples with VF4, TiF3, and VF3. The results indicate an important role of CaB6 for the reversible formation of Ca(BH4)(2).
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29.
  • Osorio, Ana, et al. (författare)
  • DNA Glycosylases Involved in Base Excision Repair May Be Associated with Cancer Risk in BRCA1 and BRCA2 Mutation Carriers.
  • 2014
  • Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 10:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Single Nucleotide Polymorphisms (SNPs) in genes involved in the DNA Base Excision Repair (BER) pathway could be associated with cancer risk in carriers of mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2, given the relation of synthetic lethality that exists between one of the components of the BER pathway, PARP1 (poly ADP ribose polymerase), and both BRCA1 and BRCA2. In the present study, we have performed a comprehensive analysis of 18 genes involved in BER using a tagging SNP approach in a large series of BRCA1 and BRCA2 mutation carriers. 144 SNPs were analyzed in a two stage study involving 23,463 carriers from the CIMBA consortium (the Consortium of Investigators of Modifiers of BRCA1 and BRCA2). Eleven SNPs showed evidence of association with breast and/or ovarian cancer at p<0.05 in the combined analysis. Four of the five genes for which strongest evidence of association was observed were DNA glycosylases. The strongest evidence was for rs1466785 in the NEIL2 (endonuclease VIII-like 2) gene (HR: 1.09, 95% CI (1.03-1.16), p = 2.7×10-3) for association with breast cancer risk in BRCA2 mutation carriers, and rs2304277 in the OGG1 (8-guanine DNA glycosylase) gene, with ovarian cancer risk in BRCA1 mutation carriers (HR: 1.12 95%CI: 1.03-1.21, p = 4.8×10-3). DNA glycosylases involved in the first steps of the BER pathway may be associated with cancer risk in BRCA1/2 mutation carriers and should be more comprehensively studied.
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30.
  • Pasquini, Luca, et al. (författare)
  • Magnesium- and intermetallic alloys-based hydrides for energy storage : modelling, synthesis and properties
  • 2022
  • Ingår i: Progress in Energy. - : Institute of Physics Publishing (IOPP). - 2516-1083. ; 4:3
  • Forskningsöversikt (refereegranskat)abstract
    • Hydrides based on magnesium and intermetallic compounds provide a viable solution to the challenge of energy storage from renewable sources, thanks to their ability to absorb and desorb hydrogen in a reversible way with a proper tuning of pressure and temperature conditions. Therefore, they are expected to play an important role in the clean energy transition and in the deployment of hydrogen as an efficient energy vector. This review, by experts of Task 40 'Energy Storage and Conversion based on Hydrogen' of the Hydrogen Technology Collaboration Programme of the International Energy Agency, reports on the latest activities of the working group 'Magnesium- and Intermetallic alloys-based Hydrides for Energy Storage'. The following topics are covered by the review: multiscale modelling of hydrides and hydrogen sorption mechanisms; synthesis and processing techniques; catalysts for hydrogen sorption in Mg; Mg-based nanostructures and new compounds; hydrides based on intermetallic TiFe alloys, high entropy alloys, Laves phases, and Pd-containing alloys. Finally, an outlook is presented on current worldwide investments and future research directions for hydrogen-based energy storage.
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31.
  • Pedersen, Helle Krogh, et al. (författare)
  • Human gut microbes impact host serum metabolome and insulin sensitivity
  • 2016
  • Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 535:7612, s. 376-381
  • Tidskriftsartikel (refereegranskat)abstract
    • Insulin resistance is a forerunner state of ischaemic cardiovascular disease and type 2 diabetes. Here we show how the human gut microbiome impacts the serum metabolome and associates with insulin resistance in 277 non-diabetic Danish individuals. The serum metabolome of insulin-resistant individuals is characterized by increased levels of branched-chain amino acids (BCAAs), which correlate with a gut microbiome that has an enriched biosynthetic potential for BCAAs and is deprived of genes encoding bacterial inward transporters for these amino acids. Prevotella copri and Bacteroides vulgatus are identified as the main species driving the association between biosynthesis of BCAAs and insulin resistance, and in mice we demonstrate that P. copri can induce insulin resistance, aggravate glucose intolerance and augment circulating levels of BCAAs. Our findings suggest that microbial targets may have the potential to diminish insulin resistance and reduce the incidence of common metabolic and cardiovascular disorders.
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32.
  • Thomassen, Mads, et al. (författare)
  • Clinical, splicing, and functional analysis to classify BRCA2 exon 3 variants : Application of a points-based ACMG/AMP approach
  • 2022
  • Ingår i: Human Mutation. - : Hindawi Limited. - 1059-7794 .- 1098-1004. ; 43:12, s. 1921-1944
  • Tidskriftsartikel (refereegranskat)abstract
    • Skipping of BRCA2 exon 3 (∆E3) is a naturally occurring splicing event, complicating clinical classification of variants that may alter ∆E3 expression. This study used multiple evidence types to assess pathogenicity of 85 variants in/near BRCA2 exon 3. Bioinformatically predicted spliceogenic variants underwent mRNA splicing analysis using minigenes and/or patient samples. ∆E3 was measured using quantitative analysis. A mouse embryonic stem cell (mESC) based assay was used to determine the impact of 18 variants on mRNA splicing and protein function. For each variant, population frequency, bioinformatic predictions, clinical data, and existing mRNA splicing and functional results were collated. Variant class was assigned using a gene-specific adaptation of ACMG/AMP guidelines, following a recently proposed points-based system. mRNA and mESC analysis combined identified six variants with transcript and/or functional profiles interpreted as loss of function. Cryptic splice site use for acceptor site variants generated a transcript encoding a shorter protein that retains activity. Overall, 69/85 (81%) variants were classified using the points-based approach. Our analysis shows the value of applying gene-specific ACMG/AMP guidelines using a points-based approach and highlights the consideration of cryptic splice site usage to appropriately assign PVS1 code strength.
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33.
  • Andersson, Mikael, 1988, et al. (författare)
  • Interplay of NH4+ and BH4- reorientational dynamics in NH4BH4
  • 2020
  • Ingår i: Physical Review Materials. - 2475-9953. ; 4:8
  • Tidskriftsartikel (refereegranskat)abstract
    • The reorientational dynamics of ammonium borohydride (NH4BH4) was studied using quasielastic neutron scattering in the temperature interval from 10 to 240 K, which covers both the dynamically ordered and disordered polymorphs of NH4BH4. In the low-temperature (50 K) ordered polymorph of NH4BH4, analysis of the quasielastic neutron scattering data reveals that no reorientational dynamics is present within the probed timescale region of 0.1 to 100 ps. In the high-temperature (50 K) disordered polymorph, the analysis establishes the onset of NH4+ and BH4- dynamics at around 50 and 125 K, respectively. The relaxation time at 150 K for NH4+ is approximately 1 ps, while around 100 ps for BH4- . The NH4+ dynamics at temperatures below 125 K is associated with preferential tetrahedral tumbling motions, where each of the hydrogen atoms in the NH4+ tetrahedron can visit any of the four hydrogen sites, however, reorientations around a specific axis are more frequently occurring (C-2 or C3). At higher temperatures, the analysis does not exclude a possible evolution of the NH4+ dynamics from tetrahedral tumbling to either cubic tumbling, where the hydrogen atoms can visit any of the eight positions corresponding to the corners of a cube, or isotropic rotational diffusion, where the hydrogen atoms can visit any location on the surface of a sphere. The BH4- dynamics can be described as cubic tumbling. The difference in reorientational dynamics between the two ions is related to the difference of the local environment where the dynamically much slower BH4- anion imposes a noncubic environment on the NH4+ cation.
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34.
  • Antoniou, Antonis C., et al. (författare)
  • Common alleles at 6q25.1 and 1p11.2 are associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers
  • 2011
  • Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 20:16, s. 3304-3321
  • Tidskriftsartikel (refereegranskat)abstract
    • Two single nucleotide polymorphisms (SNPs) at 6q25.1, near the ESR1 gene, have been implicated in the susceptibility to breast cancer for Asian (rs2046210) and European women (rs9397435). A genome-wide association study in Europeans identified two further breast cancer susceptibility variants: rs11249433 at 1p11.2 and rs999737 in RAD51L1 at 14q24.1. Although previously identified breast cancer susceptibility variants have been shown to be associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers, the involvement of these SNPs to breast cancer susceptibility in mutation carriers is currently unknown. To address this, we genotyped these SNPs in BRCA1 and BRCA2 mutation carriers from 42 studies from the Consortium of Investigators of Modifiers of BRCA1/2. In the analysis of 14 123 BRCA1 and 8053 BRCA2 mutation carriers of European ancestry, the 6q25.1 SNPs (r(2) = 0.14) were independently associated with the risk of breast cancer for BRCA1 mutation carriers [ hazard ratio (HR) = 1.17, 95% confidence interval (CI): 1.11-1.23, P-trend = 4.5 x 10(-9) for rs2046210; HR = 1.28, 95% CI: 1.18-1.40, P-trend = 1.3 x 10(-8) for rs9397435], but only rs9397435 was associated with the risk for BRCA2 carriers (HR = 1.14, 95% CI: 1.01-1.28, P-trend = 0.031). SNP rs11249433 (1p11.2) was associated with the risk of breast cancer for BRCA2 mutation carriers (HR = 1.09, 95% CI: 1.02-1.17, P-trend = 0.015), but was not associated with breast cancer risk for BRCA1 mutation carriers (HR = 0.97, 95% CI: 0.92-1.02, P-trend = 0.20). SNP rs999737 (RAD51L1) was not associated with breast cancer risk for either BRCA1 or BRCA2 mutation carriers (P-trend = 0.27 and 0.30, respectively). The identification of SNPs at 6q25.1 associated with breast cancer risk for BRCA1 mutation carriers will lead to a better understanding of the biology of tumour development in these women.
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35.
  • Arnbjerg, Lene M., et al. (författare)
  • Structure and Dynamics for LiBH4-LiCl Solid Solutions
  • 2009
  • Ingår i: Chemistry of Materials. - : American Chemical Society (ACS). - 0897-4756 .- 1520-5002. ; 21:24, s. 5772-5782
  • Tidskriftsartikel (refereegranskat)abstract
    • A Surprisingly high degree of structural and compositional dynamics is observed in the system LiBH4-LiCl as a function of temperature and time. Rietveld refinement of synchrotron radiation powder X-ray diffraction (SR-PXD) data reveals that Cl- readily substitutes for BH4- in the Structure of LiBH4. Prolonged heating a sample of LiBH4-LiCl (1:1 molar ratio) above the phase transition temperature and below the melting point (108 < T < 275 degrees C) can produce highly chloride substituted hexagonal lithium borohydride, h-Li(BH4)(l-x)Cl-x, e.g., x similar to 0.42, after heating from room temperature (RT) to 224 degrees C at 2.5 degrees C/min. LiCl has a higher solubility in h-LiBH4 its compared to orthorhombic lithium borohydride, o-LiBH4, which is illustrated by a LiBH4-LiCl (1:1) sample equilibrated at 245 degrees C for 24 days and left at RT for another 13 months. Rietveld refinement reveals that this sample contains o-Li(BH4)(0.91)Cl-0.09 and LiCl. This illustrates a significantly faster dissolution of LiCl in h-LiBH4 its compared to a slower segregation of LiCl from o-LiBH4, which is also demonstrated by in situ SR-PXD from three cycles of heating and cooling of the same Li(BH4)(0.91)Cl-0.09 sample. The substitution of the smaller Cl- for the larger BH4- ion is clearly observed as a reduction in the unit cell volume as a function of time and temperature. A significant stabilization of h-LiBH4 is found to depend on the degree of anion substitution. Variable temperature solid-state magic-angle spinning (MAS) Li-7 and B-13 NMR experiments oil pure LiBH4 show an increase in full width at half maximum (fwhm) when approaching the phase transition from o- to h-LiBH4, which indicates an increase of the relaxation rate (i.e. T-2 decreases). A less pronounced effect is observed for ion-substituted Li(BH4)(1-x)Cl-x, 0.09 < x < 0.42. The MAS NMR experiments also demonstrate a higher degree of motion in the hexagonal phase, i.e., fwhm is reduced by more than a Factor of 10 at the o- to h-LiBH4 phase transition.
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36.
  • Barkhordarian, Gagik, et al. (författare)
  • Formation of Ca(BH4)(2) from hydrogenation of CaH2+MgB2 composite
  • 2008
  • Ingår i: Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 112:7, s. 2743-2749
  • Tidskriftsartikel (refereegranskat)abstract
    • The hydrogenation of the CaH2+MgB2 Composite and the dehydrogenation of the resulting products are investigated in detail by in situ time-resolved synchrotron radiation powder X-ray diffraction, high-pressure differential scanning calorimetry, infrared, and thermovolumetric measurements. It is demonstrated that a Ca(BH4)(2)+MgH2 composite is formed by hydrogenating a CaH2+MgB2 composite, at 350 degrees C and 140 bar of hydrogen. Two phases of Ca(BH4)(2) were characterized: alpha- and beta-Ca(BH4)(2). alpha-Ca(BH4)(2) transforms to beta-Ca(BH4)(2) at about 130 degrees C. Under the conditions used in the present study, beta-Ca(BH4)(2) decomposes first to CaH2, Ca3Mg4H14, Mg, B (or MgB2 depending on experimental conditions), and hydrogen at 360 degrees C, before complete decomposition to CaH2, Mg, B (or MgB2), and hydrogen at 400 degrees C. During hydrogenation under 140 bar of hydrogen, beta-Ca(BH4)(2) is formed at 250 degrees C, and alpha-Ca(BH4)(2) is formed when the sample is cooled to less than 130 degrees C. Ti isopropoxide improves the kinetics of the reactions, during both hydrogenation and dehydrogenation. The dehydrogenation temperature decreases to 250 degrees C, with 1 wt % of this additive, and hydrogenation starts already at 200 degrees C. We propose that the improved kinetics of the above reactions with MgB2 (compared to pure boron) can be explained by the different boron bonding within the crystal structure of MgB2 and pure boron.
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37.
  • Christensen, Axel Norlund, et al. (författare)
  • Thermally induced phase transitions of barium oxalates
  • 2011
  • Ingår i: Solid State Sciences. - : Elsevier BV. - 1873-3085 .- 1293-2558. ; 13:7, s. 1407-1413
  • Tidskriftsartikel (refereegranskat)abstract
    • The thermal decomposition of BaC2O4 center dot 3.5H(2)O and BaC2O4 center dot 0.5H(2)O was investigated using in situ synchrotron X-ray and neutron powder diffraction. The decomposition routes for the barium oxalate hydrates were observed to depend on the applied heating rate. Thermal decomposition of BaC2O4 center dot 0.5H(2)O showed transformation to alpha-BaC2O4 and to beta-BaC2O4 prior to the formation of BaCO3. The decomposition of BaC2O4 center dot 3.5H(2)O showed formation of BaC2O4 center dot 0.5H(2)O at 58 degrees C and the hemi hydrate transforms to alpha-BaC2O4 at 187 degrees C using a relatively fast heating rate of 6.25 degrees C/min. The phase transitions were more complicated using lower heating rate, which also reveal formation of beta-BaC2O4 coexisting with alpha-BaC2O4 along with an unidentified compound. Heating alpha- and beta-BaC2O4 to higher temperatures (T > 400 degrees C) produced BaCO3. A sample of alpha-BaC2O4 was prepared in situ by thermal decomposition of BaC2O4 center dot 3.5H(2)O on a powder neutron diffractometer. The neutron diffraction data has broad diffraction peaks due to small crystallite sizes and overlapping Bragg reflections. [A structural model for alpha-BaC2O4 was derived from the neutron pattern, triclinic, space group P-1, a = 5.127(7), b = 8.905(12), c = 9.068(12) angstrom, alpha = 82.74(1), beta = 99.46(2), gamma = 100.10(1)degrees measured at T= 300 degrees C. The average Ba-O distances are 2.84(3) angstrom and 2.66(3) angstrom for Ba 1 and Ba2 respectively, C-O atom distances in the oxalate ions were found in the range 1.25(3)-1.26(4) angstrom, and C-C distances were 1.60(1)-1.61(1) angstrom]. (C) 2011 Elsevier Masson SAS. All rights reserved.
  •  
38.
  • Filippov, Stanislav, et al. (författare)
  • Analysis of Dihydrogen Bonding in Ammonium Borohydride
  • 2019
  • Ingår i: Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 123:47, s. 28631-28639
  • Tidskriftsartikel (refereegranskat)abstract
    • The structural and vibrational properties of ammonium borohydride, NH4BH4, have been examined by first-principles density functional theory (DFT) calculations and inelastic neutron scattering (INS). The H disordered crystal structure of NH4BH4 is composed of the tetrahedral complex ions NH4+ and BH4-, which are arranged as in the fcc NaCl structure and linked by intermolecular dihydrogen bonding. Upon cooling, the INS spectra revealed a structural transition between 45 and 40 K. The reversible transition occurs upon heating between 46 and 49 K. In the low-temperature form reorientational dynamics are frozen. The libration modes for BH4- and NH4+ are near 300 and 200 cm(-1), respectively. Upon entering the fcc high-temperature form, NH4+ ions attain fast reorientational dynamics, as indicated in the disappearance of the NH4+ libration band, whereas BH4- ions become significantly mobile only at temperatures above 100 K. The vibrational behavior of BH4- ions in NH4BH4 compares well to the heavier alkali metal borohydrides, NaBH4-CsBH4. DFT calculations revealed a nondirectional nature of the dihydrogen bonding in NH4BH4 with only weak tendency for long-range order. Different rotational configurations of complex ions appear quasi-degenerate, which is reminiscent of glasses.
  •  
39.
  • Gosalawit-Utke, Rapee, et al. (författare)
  • Ca(BH4)(2)-MgF2 Reversible Hydrogen Storage: Reaction Mechanisms and Kinetic Properties
  • 2011
  • Ingår i: Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 115:9, s. 3762-3768
  • Tidskriftsartikel (refereegranskat)abstract
    • A composite of Ca(BH4)(2)-MgF2 is proposed as a reversible hydrogen storage system. The dehydrogenation and rehydrogenation reaction mechanisms are investigated by in situ time-resolved synchrotron radiation powder X-ray diffraction (SR-PXD) and Raman spectroscopy. The formation of an intermediate phase (CaF2-xHx) is observed during rehydrogenation. The hydrogen content of 4.3 wt % is obtained within 4 h during the first dehydrogenation at isothermal and isobaric conditions of 330 degrees C and 0.5 bar H-2, respectively. The cycling efficiency is evaluated by three release and uptake cycles together with absorbed hydrogen content in the range 5.1-5.8 wt % after 2.5 h (T = 330 degrees C and p(H-2) = 130 bar). The kinetic properties on the basis of hydrogen absorption are comparable for all cycles. As compared to pure Ca(BH4)(2) and Ca(BH4)(2)-MgH2 composite, Ca(BH4)(2)-MgF2 composite reveals the kinetic destabilization and the reproducibility of hydrogen storage capacities during cycling, respectively.
  •  
40.
  • Gosalawit-Utke, Rapee, et al. (författare)
  • Nanoconfined 2LiBH(4)-MgH2 Prepared by Direct Melt Infiltration into Nanoporous Materials
  • 2011
  • Ingår i: Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 115:21, s. 10903-10910
  • Tidskriftsartikel (refereegranskat)abstract
    • Nanoconfined 2LiBH(4)-MgH2 is prepared by direct melt infiltration of bulk 2LiBH(4)-MgH2 into an inert nanoporous resorcinol-formaldehyde carbon aerogel scaffold material. Scanning electron microscopy (SEM) micrographs and energy dispersive X-ray spectroscopy (EDS) mapping reveal homogeneous dispersion of Mg (from MgH2) and B (from LiBH4) inside the carbon aerogel scaffold. Moreover, nanoconfinement of LiBH4 in the carbon aerogel scaffold is confirmed by differential scanning calorimetry (DSC). The hydrogen desorption kinetics of the nanoconfined 2LiBH(4)-MgH2 is significantly improved as compared to bulk 2LiBH(4)-MgH2. For instance, the nanoconfined 2LiBH(4)-MgH2 releases 90% of the total hydrogen storage capacity within 90 mm, whereas the bulk material releases only 34% (at T = 425 degrees C and p(H-2) = 3.4 bar). A reversible gravimetric hydrogen storage capacity of 10.8 wt % H-2, calculated with respect to the metal hydride content, is preserved over four hydrogen release and uptake cycles.
  •  
41.
  • Grinderslev, Jakob B., et al. (författare)
  • Neutron Scattering Investigations of the Global and Local Structures of Ammine Yttrium Borohydrides
  • 2021
  • Ingår i: Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 125:28, s. 15415-15423
  • Tidskriftsartikel (refereegranskat)abstract
    • Complex metal hydrides are a fascinating and continuously expanding class of materials with many properties relevant for solid-state hydrogen and ammonia storage and solid-state electrolytes. The crystal structures are often investigated using powder X-ray diffraction (PXD), which can be ambiguous. Here, we revisit the crystal structure of Y(11BD4)3·3ND3 with the use of neutron diffraction, which, in comparison to previous PXD studies, provides accurate information about the D positions in the compound. Upon cooling to 10 K, the compound underwent a polymorphic transition, and a new monoclinic low-temperature polymorph denoted as α-Y(11BD4)3·3ND3 was discovered. Furthermore, the series of Y(11BH4)3·xNH3 (x = 0, 3, and 7) were also investigated with inelastic neutron scattering and infrared spectroscopy techniques, which provided information of the local coordination environment of the 11BH4- and NH3 groups and unique insights into the hydrogen dynamics. Partial deuteration using ND3 in Y(11BH4)3·xND3 (x = 3 and 7) allowed for an unambiguous assignment of the vibrational bands corresponding to the NH3 and 11BH4- in Y(11BH4)3·xNH3, due to the much larger neutron scattering cross section of H compared to D. The vibrational spectra of Y(11BH4)3·xNH3 could roughly be divided into three regions: (i) below 55 meV, containing mainly 11BH4- librational motions, (ii) 55-130 meV, containing mainly NH3 librational motions, and (iii) above 130 meV, containing 11B-H and N-H bending and stretching motions.
  •  
42.
  • Grinderslev, Jakob B., et al. (författare)
  • Reorientational Dynamics in Y(BH 4 ) 3 ·xNH 3 (x = 0, 3, and 7): The Impact of NH 3 on BH 4 - Dynamics
  • 2024
  • Ingår i: Journal of Physical Chemistry C. - 1932-7447 .- 1932-7455. ; 128:11, s. 4431-4439
  • Tidskriftsartikel (refereegranskat)abstract
    • The reorientational dynamics of Y(BH4)3·xNH3 (x = 0, 3, and 7) was studied using quasielastic neutron scattering (QENS) and neutron spin echo (NSE). The results showed that changing the number of NH3 ligands drastically alters the reorientational mobility of the BH4- anion. From the QENS experiments, it was determined that the BH4- anion performs 2-fold reorientations around the C2 axis in Y(BH4)3, 3-fold reorientations around the C3 axis in Y(BH4)3·3NH3, and either 2-fold reorientations around the C2 axis or 3-fold reorientations around the C3 axis in Y(BH4)3·7NH3. The relaxation time of the BH4- anion at 300 K decreases from 2 × 10-7 s for x = 0 to 1 × 10-12 s for x = 3 and to 7 × 10-13 s for x = 7. In addition to the reorientational dynamics of the BH4- anion, it was shown that the NH3 ligands exhibit 3-fold reorientations around the C3 axis in Y(BH4)3·3NH3 and Y(BH4)3·7NH3 as well as 3-fold quantum mechanical rotational tunneling around the same axis at 5 K. The new insights constitute a significant step toward understanding the relationship between the addition of ligands and the enhanced ionic conductivity observed in systems such as LiBH4·xNH3 and Mg(BH4)2·xCH3NH2
  •  
43.
  • Hirscher, Michael, et al. (författare)
  • Materials for hydrogen-based energy storage - past, recent progress and future outlook
  • 2020
  • Ingår i: Journal of Alloys and Compounds. - : Elsevier BV. - 0925-8388 .- 1873-4669. ; 827
  • Tidskriftsartikel (refereegranskat)abstract
    • Globally, the accelerating use of renewable energy sources, enabled by increased efficiencies and reduced costs, and driven by the need to mitigate the effects of climate change, has significantly increased research in the areas of renewable energy production, storage, distribution and end-use. Central to this discussion is the use of hydrogen, as a clean, efficient energy vector for energy storage. This review, by experts of Task 32, Hydrogen-based Energy Storage of the International Energy Agency, Hydrogen TCP, reports on the development over the last 6 years of hydrogen storage materials, methods and techniques, including electrochemical and thermal storage systems. An overview is given on the background to the various methods, the current state of development and the future prospects. The following areas are covered; porous materials, liquid hydrogen carriers, complex hydrides, intermetallic hydrides, electrochemical storage of energy, thermal energy storage, hydrogen energy systems and an outlook is presented for future prospects and research on hydrogen-based energy storage.
  •  
44.
  • Jensen, Torben R., et al. (författare)
  • Versatile in situ powder X-ray diffraction cells for solid-gas investigations
  • 2010
  • Ingår i: Journal of Applied Crystallography. - 1600-5767. ; 43, s. 1456-1463
  • Tidskriftsartikel (refereegranskat)abstract
    • This paper describes new sample cells and techniques for in situ powder X-ray diffraction specifically designed for gas absorption studies up to ca 300 bar (1 bar = 100 000 Pa) gas pressure. The cells are for multipurpose use, in particular the study of solid-gas reactions in dosing or flow mode, but can also handle samples involved in solid-liquid-gas studies. The sample can be loaded into a single-crystal sapphire (Al2O3) capillary, or a quartz (SiO2) capillary closed at one end. The advantages of a sapphire single-crystal cell with regard to rapid pressure cycling are discussed, and burst pressures are calculated and measured to be similar to 300 bar. An alternative and simpler cell based on a thin-walled silicate or quartz glass capillary, connected to a gas source via a VCR fitting, enables studies up to similar to 100 bar. Advantages of the two cell types are compared and their applications are illustrated by case studies.
  •  
45.
  • Korablov, Dmytro, et al. (författare)
  • Activation effects during hydrogen release and uptake of MgH2
  • 2014
  • Ingår i: International journal of hydrogen energy. - : Elsevier BV. - 0360-3199 .- 1879-3487. ; 39:18, s. 9888-9892
  • Tidskriftsartikel (refereegranskat)abstract
    • Scandium(II)hydride, ScH2, and scandium(III)chloride, ScCl3, are explored as additives to facilitate hydrogen release and uptake for magnesium hydride. These additives are expected to form more homogeneous composites with Mg/MgH2 as compared to metallic scandium. However, scandium(III)chloride, reacts with MgH2 during mechano-chemical treatment and form ScH2 and MgCl2 (that later crystallise during heat treatment). The composite MgH2-ScH2 was investigated using in-situ synchrotron radiation powder X-ray diffraction during up to five cycles of continuous release and uptake of hydrogen at isothermal conditions at 320, 400 and 450 degrees C and p(H-2) = 100-150 or 10(-2) bar. The data were analysed by Rietveld refinement and no reaction is observed between either MgH2/ScH2 or Mg/ScH2 during cycling. The extracted sigmoidal shaped curves for formation or decomposition of Mg/MgH2 suggest that a nucleation process is preceding the crystal growth. The reaction rate increases with increasing number of cycles of hydrogen release and uptake at isothermal conditions possibly due to activation effects. This kinetic enhancement is strongest between the first cycles and may be denoted an activation effect. Copyright (C) 2014, Hydrogen Energy Publications, LLC. Published by Elsevier Ltd. All rights reserved.
  •  
46.
  • Lee, Ji Youn, et al. (författare)
  • Decomposition Reactions and Reversibility of the LiBH4-Ca(BH4)(2) Composite
  • 2009
  • Ingår i: Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 113:33, s. 15080-15086
  • Tidskriftsartikel (refereegranskat)abstract
    • LiBH4 is one of the promising candidates for hydrogen storage materials because of its high gravimetric and volumetric hydrogen capacity. However, its high dehydrogenation temperature and limited reversibility has been a hurdle for its use in real applications. In an effort to overcome this barrier and to adjust the thermal stability, we make a composite system LiBH4-Ca(BH4)(2). In order to fully characterize this composite system we study xLiBH(4) + (1 - x)Ca(BH4)(2) for several x values between 0 and 1, using differential scanning calorimetry, in situ synchrotron X-ray diffraction, thermogravimetric analysis, and mass spectrometry. Interestingly, this composite undergoes a eutectic melting at ca. 200 degrees C in a wide composition range, and the eutectic composition lies between x = 0.6 and 0.8. The decomposition characteristics and the hydrogen capacity of this composite vary with x, and the decomposition temperature is lower than both the pure LiBH4 and Ca(BH4)(2) at intermediate conpositions, for example, for x approximate to 0.4, decomposition is finished below 400 degrees C releasing about 10 wt % of hydrogen. Partial reversibility of this system was also confirmed for the first time for the case of if mixed borohydride composite.
  •  
47.
  • Moghadasi, Setareh, et al. (författare)
  • The BRCA1 c. 5096G > A p.Arg1699Gln (R1699Q) intermediate risk variant : breast and ovarian cancer risk estimation and recommendations for clinical management from the ENIGMA consortium
  • 2018
  • Ingår i: Journal of Medical Genetics. - : BMJ PUBLISHING GROUP. - 0022-2593 .- 1468-6244. ; 55:1, s. 15-20
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: We previously showed that the BRCA1 variant c. 5096G> A p.Arg1699Gln (R1699Q) was associated with an intermediate risk of breast cancer (BC) and ovarian cancer (OC). This study aimed to assess these cancer risks for R1699Q carriers in a larger cohort, including follow-up of previously studied families, to further define cancer risks and to propose adjusted clinical management of female BRCA1* R1699Q carriers.Methods: Data were collected from 129 BRCA1* R1699Q families ascertained internationally by ENIGMA (Evidence-based Network for the Interpretation of Germline Mutant Alleles) consortium members. A modified segregation analysis was used to calculate BC and OC risks. Relative risks were calculated under both monogenic model and major gene plus polygenic model assumptions.Results: In this cohort the cumulative risk of BC and OC by age 70 years was 20% and 6%, respectively. The relative risk for developing cancer was higher when using a model that included the effects of both the R1699Q variant and a residual polygenic component compared with monogenic model (for BC 3.67 vs 2.83, and for OC 6.41 vs 5.83).Conclusion: O ur results confirm that BRCA1* R1699Q confers an intermediate risk for BC and OC. Breast surveillance for female carriers based on mammogram annually from age 40 is advised. Bilateral salpingooophorectomy should be considered based on family history.
  •  
48.
  • Mosegaard, Lene, et al. (författare)
  • Intermediate phases observed during decomposition of LiBH4
  • 2007
  • Ingår i: Journal of Alloys and Compounds. - 0925-8388. ; 446-447, s. 301-305
  • Konferensbidrag (refereegranskat)abstract
    • Lithium tetrahydridoboranate is among the materials with the highest hydrogen content and has great potential as a possible H-2-storage material, although, the release and uptake of H-2 is not fully understood. In this work, LiBH4 was studied by in situ synchrotron radiation powder X-ray diffraction (PXD) and solid state CP/MAS NNIR both at variable temperatures. This study revealed two new phases observed during dehydrogenation of LiBH4. Phase I is hexagonal, a = 4.93(2) and c = 13.47(3) angstrom and is observed in the temperature range -200-300 degrees C, and phase II is orthorhombic, a = 8.70(1), b = 5.44(1) and c = 4.44](8) angstrom and is observed in the temperature range similar to 300-400 degrees C applying a constant heating rate of 5 degrees C/min. Apparently, I transforms into II, e.g. at a constant temperature of T= 265 degrees C after 5 h. Furthermore, a third phase, III, is observed in the temperature range RT to 70 degrees C, and is caused by a reaction between LiBH4 and water vapor from the atmosphere. Hydrogen release is associated with the decomposition of III at ca. 65 degrees C. (C) 2007 Elsevier B.V. All rights reserved.
  •  
49.
  • Mosegaard, Lene, et al. (författare)
  • Reactivity of LiBH4: In situ synchrotron radiation powder X-ray diffraction study
  • 2008
  • Ingår i: Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 112:4, s. 1299-1303
  • Tidskriftsartikel (refereegranskat)abstract
    • Lithium tetrahydridoboranate (LiBH4) may be a potentially interesting material for hydrogen storage, but in order to absorb and desorb hydrogen routinely and reversibly, the kinetics and thermodynamics need to be improved significantly. A priori, this material has one of the highest theoretical gravimetric hydrogen contents, 18.5 wt%, but unfortunately for practical applications, hydrogen release occurs at too high temperature in a non-reversible way. By means of in situ synchrotron radiation powder X-ray diffraction (SR-PXD), the interaction between LiBH4 and different additives-SiO2, TiCl3, LiCl, and Au - is investigated. It is found that silicon dioxide reacts with molten LiBH4 and forms Li2SiO3 or Li4SiO4 at relatively low amounts of SiO2, e.g., with 5.0 and 9.9 mol % SiO2 in LiBH4, Whereas, for higher amounts of SiO2 (e.g., 25.5 mol %), only the Li2SiO3 phase is observed. Furthermore, we demonstrate that a solid-state reaction occurs between LiBH4 and TiCl3 to form LiCl at room temperature. At elevated temperatures, more LiCl is formed simultaneously with a decrease in the diffracted intensity from TiCl3. Lithium chloride shows some solubility in solid LiBH4 at T > 100 degrees C. This is the first report of substituents that accommodate the structure of LiBH4 by a solid/solid dissolution reaction. Gold is found to react with molten LiBH4 forming a Li-Au alloy with CuAu3-type structure. These studies demonstrate that molten LiBH4 has a high reactivity, and finding a catalyst for this H-rich system may be a challenge.
  •  
50.
  • Nielsen, Thomas K., et al. (författare)
  • A Reversible Nanoconfined Chemical Reaction
  • 2010
  • Ingår i: ACS Nano. - : American Chemical Society (ACS). - 1936-086X .- 1936-0851. ; 4:7, s. 3903-3908
  • Tidskriftsartikel (refereegranskat)abstract
    • Hydrogen is recognized as a potential, extremely interesting energy carrier system, which can facilitate efficient utilization of unevenly distributed renewable energy. A major challenge in a future "hydrogen economy" is the development of a safe, compact, robust, and efficient means of hydrogen storage, in particular, for mobile applications. Here we report on a new concept for hydrogen storage using nanoconfined reversible chemical reactions. LiBH4 and MgH2 nanoparticles are embedded in a nanoporous carbon aerogel scaffold with pore size D-max similar to 21 nm and react during release of hydrogen and form MgB2. The hydrogen desorption kinetics is significantly improved compared to bulk conditions, and the nanoconfined system has a high degree of reversibility and stability and possibly also improved thermodynamic properties. This new scheme of nanoconfined chemistry may have a wide range of interesting applications in the future, for example, within the merging area of chemical storage of renewable energy.
  •  
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