| 1. |
- Karlsson, Mattias, 1980, et al.
(författare)
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Biomimetic nanoscale reactors and networks
- 2004
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Ingår i: Annual Review of Physical Chemistry. - : Annual Reviews. - 0066-426X .- 1545-1593. ; 55, s. 613-49
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Tidskriftsartikel (refereegranskat)abstract
- Methods based on self-assembly, self-organization, and forced shape transformations to form synthetic or semisynthetic enclosed lipid bilayer structures with several properties similar to biological nanocompartments are reviewed. The procedures offer unconventional micro- and nanofabrication routes to yield complex soft-matter devices for a variety of applications for example, in physical chemistry and nanotechnology. In particular, we describe novel micromanipulation methods for producing fluid-state lipid bilayer networks of nanotubes and surface-immobilized vesicles with controlled geometry, topology, membrane composition, and interior contents. Mass transport in nanotubes and materials exchange, for example, between conjugated containers, can be controlled by creating a surface tension gradient that gives rise to a moving boundary or by induced shape transformations. The network devices can operate with extremely small volume elements and low mass, to the limit of single molecules and particles at a length scale where a continuum mechanics approximation may break down. Thus, we also describe some concepts of anomalous fluctuation-dominated kinetics and anomalous diffusive behaviours, including hindered transport, as they might become important in studying chemistry and transport phenomena in these confined systems. The networks are suitable for initiating and controlling chemical reactions in confined biomimetic compartments for rationalizing, for example, enzyme behaviors, as well as for applications in nanofluidics, bioanalytical devices, and to construct computational and complex sensor systems with operations building on chemical kinetics, coupled reactions and controlled mass transport.
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| 2. |
- Karlsson, Mattias, 1980, et al.
(författare)
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Micropipet-assisted formation of microscopic networks of unilamellar lipid bilayer nanotubes and containers
- 2001
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Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 17:22, s. 6754-6758
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Tidskriftsartikel (refereegranskat)abstract
- We describe a novel micropipet-assisted technique for the construction of complex, surface-immobilized two-dimensional microscopic networks of unilamellar phospholipid bilayer vesicles (1-50 pm in diameter, 10(-15)-10(-12) L) interconnected by lipid nanotubes (100-300 nm in diameter). As starting material for the construction of networks, we used twinned vesicle pairs, one of which is multilamellar and functions as a membrane donor and the other unilamellar and functions as a membrane acceptor upon manipulation. By electromechanical insertion of a pipet tip into the unilamellar vesicle followed by lateral pulling of the micropipet away from the vesicle, a nanotube was formed. Buffer solution contained in the pipet was then injected into the nanotube orifice, forming a vesicle of controlled size that was immobilized on the surface. The networks have controlled connectivity and are well-defined with regard to the container size, angle between nanotube extensions, and nanotube length. The internal fluid composition of individual vesicles is defined during the formation of a network by selection of the solution contained in the micropipet.
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| 3. |
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| 4. |
- Grinderslev, Jakob B., et al.
(författare)
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Neutron Scattering Investigations of the Global and Local Structures of Ammine Yttrium Borohydrides
- 2021
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Ingår i: Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 125:28, s. 15415-15423
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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.
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| 5. |
- Nedumkandathil, Reji, et al.
(författare)
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Hydride Reduction of BaTiO3 ? Oxyhydride Versus O Vacancy Formation
- 2018
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Ingår i: ACS Omega. - : American Chemical Society (ACS). - 2470-1343. ; 3:9, s. 11426-11438
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Tidskriftsartikel (refereegranskat)abstract
- We investigated the hydride reduction of tetragonal BaTiO3 using the metal hydrides CaH2, NaH, MgH2, NaBH4, and NaAlH4. The reactions employed molar BaTiO3/H ratios of up to 1.8 and temperatures near 600 °C. The air-stable reduced products were characterized by powder X-ray diffraction (PXRD), transmission electron microscopy, thermogravimetric analysis (TGA), and 1H magic angle spinning (MAS) NMR spectroscopy. PXRD showed the formation of cubic products - indicative of the formation of BaTiO3-xHx - except for NaH. Lattice parameters were in a range between 4.005 Å (for NaBH4-reduced samples) and 4.033 Å (for MgH2-reduced samples). With increasing H/BaTiO3 ratio, CaH2-, NaAlH4-, and MgH2-reduced samples were afforded as two-phase mixtures. TGA in air flow showed significant weight increases of up to 3.5% for reduced BaTiO3, suggesting that metal hydride reduction yielded oxyhydrides BaTiO3-xHx with x values larger than 0.5. 1H MAS NMR spectroscopy, however, revealed rather low concentrations of H and thus a simultaneous presence of O vacancies in reduced BaTiO3. It has to be concluded that hydride reduction of BaTiO3 yields complex disordered materials BaTiO3-xHy?(x-y) with x up to 0.6 and y in a range 0.04-0.25, rather than homogeneous solid solutions BaTiO3-xHx. Resonances of (hydridic) H substituting O in the cubic perovskite structure appear in the ?2 to ?60 ppm spectral region. The large range of negative chemical shifts and breadth of the signals signifies metallic conductivity and structural disorder in BaTiO3-xHy?(x-y). Sintering of BaTiO3-xHy?(x-y) in a gaseous H2 atmosphere resulted in more ordered materials, as indicated by considerably sharper 1H resonances.
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| 6. |
- Nzulu, Gabriel Kofi, 1974-, et al.
(författare)
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Growth and thermal stability of Sc-doped BaZrO 3 thin films deposited on single crystal substrates
- 2023
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Ingår i: Thin Solid Films. - : Elsevier BV. - 0040-6090 .- 1879-2731. ; 772
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Tidskriftsartikel (refereegranskat)abstract
- Thin films of BaZr1-xScxO3-x/2, (0 ≤ x ≤ 0.64), well known as proton conducting solid electrolytes for intermediate temperature solid oxide fuel cell, were deposited by magnetron sputtering. X-ray diffraction analysis of the as deposited films reveals the presence of single-phase perovskite structure. The films were deposited on four different substrates (c-Al2O3, LaAlO3〈100〉, LaAlO3〈110〉, LaAlO3〈111〉) yielding random, (110)- or (100)-oriented films. The stability of the as-deposited films was assessed by annealing in air at 600 °C for 2 h. The annealing treatment revealed instabilities of the perovskite structure for the (110) and randomly oriented films, but not for (100) oriented film. The instability of the coating under heat treatment was attributed to the low oxygen content in the film (understoichiometry) prior annealing combined with the surface energy and atomic layers stacking along the growth direction. An understoichiometric (100) oriented perovskite films showed higher stability of the structure under an annealing in air at 600 °C.
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| 7. |
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| 8. |
- Aidanpää, Jan-Olov, et al.
(författare)
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Developments in rotor dynamical modeling of hydropower units
- 2009
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Ingår i: Proceedings of the IUTAM Symposium on Emerging Trends in Rotor Dynamics. - Dordrecht : Encyclopedia of Global Archaeology/Springer Verlag. - 9789400700192
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Konferensbidrag (refereegranskat)
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| 9. |
- Davidson, M., et al.
(författare)
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Fluid mixing in growing microscale vesicles conjugated by surfactant nanotubes
- 2005
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 1520-5126 .- 0002-7863. ; 127:4, s. 1251-1257
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Tidskriftsartikel (refereegranskat)abstract
- This work addresses novel means for controlled mixing and reaction initiation in biomimetic confined compartments having volume elements in the range of 10-12 to 10-15 L. The method is based on mixing fluids using a two-site injection scheme into growing surfactant vesicles. A solid-state injection needle is inserted into a micrometer-sized vesicle (radius 5-25 μm), and by pulling on the needle, we create a nanoscale surfactant channel connecting injection needle and the vesicle. Injection of a solvent A from the needle into the nanotube results in the formation of a growing daughter vesicle at the tip of the needle in which mixing takes place. The growth of the daughter vesicle requires a flow of surfactants in the nanotube that generates a flow of solvent B inside the nanotube which is counterdirectional to the pressure-injected solvent. The volume ratio ψ between solvent A and B inside the mixing vesicle was analyzed and found to depend only on geometrical quantities. The majority of fluid injected to the growing daughter vesicle comes from the pressure-based injection, and for a micrometer-sized vesicle it dominates. For the formation of one daughter vesicle (conjugated with a 100-nm radius tube) expanded from 1 to 200 μm in radius, the mixing ratios cover almost 3 orders of magnitude. We show that the system can be expanded to linear strings of nanotube-conjugated vesicles that display exponential dilution. Mixing ratios spanning 6 orders of magnitude were obtained in strings of three nanotube-conjugated micrometer-sized daughter vesicles.
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| 10. |
- 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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| 11. |
- Eriksson, Anna L, et al.
(författare)
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Serum Glycine Levels Are Associated With Cortical Bone Properties and Fracture Risk in Men.
- 2021
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 106:12
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Tidskriftsartikel (refereegranskat)abstract
- In a recent study a pattern of 27 metabolites, including serum glycine, associated with bone mineral density (BMD).To investigate associations for serum and urinary glycine levels with BMD, bone microstructure, and fracture risk in men.In the population-based Osteoporotic Fractures in Men (MrOS) Sweden study (men, 69-81 years) serum glycine and BMD were measured at baseline (n=965) and 5-year follow-up (n=546). Cortical and trabecular bone parameters of the distal tibia were measured at follow-up using high-resolution peripheral quantitative computed tomography. Urinary (n=2682) glycine was analyzed at baseline. X-ray-validated fractures (n=594) were ascertained during a median follow-up of 9.6 years. Associations were evaluated using linear regression (bone parameters) or Cox regression (fractures).Circulating glycine levels were inversely associated with femoral neck (FN)-BMD. A meta-analysis (n=7543) combining MrOS Sweden data with data from 3 other cohorts confirmed a robust inverse association between serum glycine levels and FN-BMD (P=7.7×10-9). Serum glycine was inversely associated with the bone strength parameter failure load in the distal tibia (P=0.002), mainly as a consequence of an inverse association with cortical cross-sectional area and a direct association with cortical porosity. Both serum and urinary glycine levels predicted major osteoporotic fractures (serum: hazard ratio [HR] per SD increase=1.22, 95% CI, 1.05-1.43; urine: HR=1.13, 95% CI, 1.02-1.24). These fracture associations were only marginally reduced in models adjusted by FRAX with BMD.Serum and urinary glycine are indirectly associated with FN-BMD and cortical bone strength, and directly associated with fracture risk in men.
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| 12. |
- Hurtig, Johan, 1974, et al.
(författare)
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Topographic SU 8 Substrates for Immobilization of Three-Dimensional Nanotube-Vesicle Networks
- 2004
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Ingår i: Langmuir. - : American Chemical Society (ACS). - 1520-5827 .- 0743-7463. ; 20:13, s. 5637-5641
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Tidskriftsartikel (refereegranskat)abstract
- A method to create three-dimensional compact liposome networks, adhered to topographic substrates fabricated in the epoxy polymer SU-8 was described. The polymeric photoresist SU-8 is a highly suitable material for soybean lipid vesicle immobilization displaying sufficient contact potential for secure anchoring of liposomes and minimal lipid spreading. The material allows fluid-state lipid membrane structures to retain their structural integrity for long time periods. The use of the construction techniques increases the compactness of lipid nanotube networks as the tube density from a single vesicle is increased when access to the off-equatorial area is provided.
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| 13. |
- Hutchinson, B., et al.
(författare)
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Microstructures and hardness of as-quenched martensites (0.1-0.5%C)
- 2011
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Ingår i: Acta Materialia. - : Elsevier BV. - 1359-6454 .- 1873-2453. ; 59:14, s. 5845-5858
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Tidskriftsartikel (refereegranskat)abstract
- Four commercial steels with carbon contents in the range 0.1-0.5 wt.% have been examined in the as-quenched condition using electron microscopy, X-ray diffraction and atom probe tomography. The austenite had been deformed 0%, 10% and 30% prior to brine quenching. No influence of this deformation was evident on the martensite hardness or in any of the microstructure measurements. Increasing carbon content showed a well-known marked effect on the hardness but resulted in little refinement in the grain structure of the martensite. All crystal structures were cubic; no evidence of tetragonality was seen even at the highest carbon level but some systematic changes in grain boundary misorientations existed. The content of carbon in true interstitial solid solution deduced from X-ray line shifts was small (similar to 0.02 wt.%), and was independent of the total carbon content in the steel. Atom probe tomography showed that carbon was almost completely segregated to lath boundaries and dislocations but with an increasing density of segregates in the higher carbon steels. Calculations of diffusion distances confirmed that the segregation patterns were compatible with autotempering of the martensite during quenching. Analysis of different possible contributions to strength leads to the conclusion that segregated carbon atoms at defects behave similarly to carbon in true solid solution and that this is the largest single factor controlling the strength of as-quenched martensite. (C) 2011 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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| 14. |
- Karasik, D., et al.
(författare)
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Disentangling the genetics of lean mass
- 2019
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Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 109:2, s. 276-287
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Tidskriftsartikel (refereegranskat)abstract
- Background: Lean body mass (LM) plays an important role in mobility and metabolic function. We previously identified five loci associated with LM adjusted for fat mass in kilograms. Such an adjustment may reduce the power to identify genetic signals having an association with both lean mass and fat mass. Objectives: To determine the impact of different fat mass adjustments on genetic architecture of LM and identify additional LM loci. Methods: We performed genome-wide association analyses for whole-body LM (20 cohorts of European ancestry with n = 38,292) measured using dual-energy X-ray absorptiometry) or bioelectrical impedance analysis, adjusted for sex, age, age(2), and height with or without fat mass adjustments (Model 1 no fat adjustment; Model 2 adjustment for fat mass as a percentage of body mass; Model 3 adjustment for fat mass in kilograms). Results: Seven single-nucleotide polymorphisms (SNPs) in separate loci, including one novel LM locus (TNRC6B), were successfully replicated in an additional 47,227 individuals from 29 cohorts. Based on the strengths of the associations in Model 1 vs Model 3, we divided the LM loci into those with an effect on both lean mass and fat mass in the same direction and refer to those as "sumo wrestler" loci (FTO and MC4R). In contrast, loci with an impact specifically on LMwere termed "body builder" loci (VCAN and ADAMTSL3). Using existing available genome-wide association study databases, LM increasing alleles of SNPs in sumo wrestler loci were associated with an adverse metabolic profile, whereas LM increasing alleles of SNPs in "body builder" loci were associated with metabolic protection. Conclusions: In conclusion, we identified one novel LM locus (TNRC6B). Our results suggest that a genetically determined increase in lean mass might exert either harmful or protective effects on metabolic traits, depending on its relation to fat mass.
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| 15. |
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| 16. |
- Manousaki, D., et al.
(författare)
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Low-Frequency Synonymous Coding Variation in CYP2R1 Has Large Effects on Vitamin D Levels and Risk of Multiple Sclerosis
- 2017
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 101:2, s. 227-238
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Tidskriftsartikel (refereegranskat)abstract
- Vitamin D insufficiency is common, correctable, and influenced by genetic factors, and it has been associated with risk of several diseases. We sought to identify low-frequency genetic variants that strongly increase the risk of vitamin D insufficiency and tested their effect on risk of multiple sclerosis, a disease influenced by low vitamin D concentrations. We used whole-genome sequencing data from 2,619 individuals through the UK10K program and deep-imputation data from 39,655 individuals genotyped genome-wide. Meta-analysis of the summary statistics from 19 cohorts identified in CYP2R1 the low-frequency (minor allele frequency = 2.5%) synonymous coding variant g.14900931G>A (p.Asp120Asp) (rs117913124[A]), which conferred a large effect on 25-hydroxyvitamin D (25OHD) levels (-0.43 SD of standardized natural log-transformed 25OHD per A allele; p value = 1.5 x 10(-88)). The effect on 25OHD was four times larger and independent of the effect of a previously described common variant near CYP2R1. By analyzing 8,711 individuals, we showed that heterozygote carriers of this low-frequency variant have an increased risk of vitamin D insufficiency (odds ratio [OR] = 2.2, 95% confidence interval [CI] = 1.78-2.78, p = 1.26 3 10 x(-12)). Individuals carrying one copy of this variant also had increased odds of multiple sclerosis (OR = 1.4, 95% CI = 1.19-1.64, p = 2.63 3 10 x(-5)) in a sample of 5,927 case and 5,599 control subjects. In conclusion, we describe a low-frequency CYP2R1 coding variant that exerts the largest effect upon 25OHD levels identified to date in the general European population and implicates vitamin D in the etiology of multiple sclerosis.
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| 17. |
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| 18. |
- Nethander, Maria, 1980, et al.
(författare)
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BMD-Related Genetic Risk Scores Predict Site-Specific Fractures as Well as Trabecular and Cortical Bone Microstructure
- 2020
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 105:4
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: It is important to identify patients at highest risk of fractures. OBJECTIVE: To compare the separate and combined performances of bone-related genetic risk scores (GRSs) for prediction of forearm, hip and vertebral fractures separately, as well as of trabecular and cortical bone microstructure parameters separately. DESIGN, SETTING, AND PARTICIPANTS: Using 1103 single nucleotide polymorphisms (SNPs) independently associated with estimated bone mineral density of the heel (eBMD), we developed a weighted GRS for eBMD and determined its contribution to fracture prediction beyond 2 previously developed GRSs for femur neck BMD (49 SNPs) and lumbar spine BMD (48 SNPs). Associations between these GRSs and forearm (ncases = 1020; ncontrols = 2838), hip (ncases = 1123; ncontrols = 2630) and vertebral (ncases = 288; ncontrols = 1187) fractures were evaluated in 3 Swedish cohorts. Associations between the GRSs and trabecular and cortical bone microstructure parameters (n = 426) were evaluated in the MrOS Sweden cohort. RESULTS: We found that eBMDGRS was the only significant independent predictor of forearm and vertebral fractures while both FN-BMDGRS and eBMDGRS were significant independent predictors of hip fractures. The eBMDGRS was the major GRS contributing to prediction of trabecular bone microstructure parameters while both FN-BMDGRS and eBMDGRS contributed information for prediction of cortical bone microstructure parameters. CONCLUSIONS: The eBMDGRS independently predicts forearm and vertebral fractures while both FN-BMDGRS and eBMDGRS contribute independent information for prediction of hip fractures. We propose that eBMDGRS captures unique information about trabecular bone microstructure useful for prediction of forearm and vertebral fractures. These findings may facilitate personalized medicine to predict site-specific fractures as well as cortical and trabecular bone microstructure separately.
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| 19. |
- Nilsson, Fritjof, Docent, 1978-, et al.
(författare)
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Nanocomposites and polyethylene blends: two potentially synergistic strategies for HVDC insulation materials with ultra-low electrical conductivity
- 2021
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Ingår i: Composites Part B: Engineering. - : Elsevier BV. - 1359-8368 .- 1879-1069. ; 204
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Tidskriftsartikel (refereegranskat)abstract
- Among the various requirements that high voltage direct current (HVDC) insulation materials need to satisfy, sufficiently low electrical conductivity is one of the most important. The leading commercial HVDC insulation material is currently an exceptionally clean cross-linked low-density polyethylene (XLPE). Previous studies have reported that the DC-conductivity of low-density polyethylene (LDPE) can be markedly reduced either by including a fraction of high-density polyethylene (HDPE) or by adding a small amount of a well dispersed, semiconducting nanofiller such as Al2O3 coated with a silane. This study demonstrates that by combining these two strategies a synergistic effect can be achieved, resulting in an insulation material with an ultra-low electrical conductivity. The addition of both HDPE and C8–Al2O3 nanoparticles to LDPE resulted in ultra-insulating nanocomposites with a conductivity around 500 times lower than of the neat LDPE at an electric field of 32 kV/mm and 60–90 °C. The new nanocomposite is thus a promising material regarding the electrical conductivity and it can be further optimized since the polyethylene blend and the nanoparticles can be improved independently.
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| 20. |
- Ohlsson, Claes, 1965, et al.
(författare)
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Low Serum DHEAS Predicts Increased Fracture Risk in Older Men: The MrOS Sweden Study
- 2017
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 32:8, s. 1607-1614
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Tidskriftsartikel (refereegranskat)abstract
- The adrenal-derived hormones dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) are the most abundant circulating hormones and their levels decline substantially with age. DHEAS is considered an inactive precursor, which is converted into androgens and estrogens via local metabolism in peripheral target tissues. The predictive value of serum DHEAS for fracture risk is unknown. The aim of this study was, therefore, to assess the associations between baseline DHEAS levels and incident fractures in a large cohort of older men. Serum DHEAS levels were analyzed with mass spectrometry in the population-based Osteoporotic Fractures in Men study in Sweden (n = 2568, aged 69 to 81 years). Incident X-ray validated fractures (all, n = 594; non-vertebral major osteoporotic, n = 255; hip, n = 175; clinical vertebral, n = 206) were ascertained during a median follow-up of 10.6 years. DHEAS levels were inversely associated with the risk of any fracture (hazard ratio [HR] per SD decrease = 1.14, 95% confidence interval [CI] 1.05-1.24), non-vertebral major osteoporotic fractures (HR = 1.31, 95% CI 1.16-1.48), and hip fractures (HR = 1.18, 95% CI 1.02-1.37) but not clinical vertebral fractures (HR = 1.09, 95% CI 0.95-1.26) in Cox regression models adjusted for age, body mass index (BMI) and prevalent fractures. Further adjustment for traditional risk factors for fracture, bone mineral density (BMD), and/or physical performance variables as well as serum sex steroid levels only slightly attenuated the associations between serum DHEAS and fracture risk. Similarly, the point estimates were only marginally reduced after adjustment for FRAX estimates with BMD. The inverse association between serum DHEAS and all fractures or major osteoporotic fractures was nonlinear, with a substantial increase in fracture risk (all fractures 22%, major osteoporotic fractures 33%) for those participants with serum DHEAS levels below the median (0.60 mg/mL). In conclusion, low serum DHEAS levels are a risk marker of mainly non-vertebral fractures in older men, of whom those with DHEAS levels below 0.60 mg/mL are at highest risk. (C) The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.
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| 21. |
- Olofsson, Jessica, 1975, et al.
(författare)
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A microfluidics approach to the problem of creating separate solution environments accessible from macroscopic volumes
- 2004
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Ingår i: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 76:17, s. 4968-4976
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Tidskriftsartikel (refereegranskat)abstract
- We report on a microfluidic device that generates separate solution environments in macroscopic volumes. Spatially distinct patterns are created by emitting fluids from 16 different sources (closely spaced microchannels) into a solution-filled macroscopic chamber. The fluid in neighboring microchannels couples viscously in the macroscopic container, generating one single interdigitated stream. Scanning nanoelectrode amperometry was used for characterizing the concentration landscape and the diffusion zones between solutions running in parallel at different coordinates in the stream. These experiments were complemented by finite element simulations of the Navier-Stokes and mass transport equations to describe the velocity distributions and the diffusion behavior. For in channel flow velocities of 50 mm·s -1 , patterns could persist on the order of millimeters to centimeters in the open volume. The most narrow diffusion zones with widths less than 10 μm (5-95% concentration change) were found some tens of micrometers out in the macroscopic container. We demonstrate that a 14-μm-diameter nearly spherical object (biological cell) attached to a micropipet can be moved from one solution environment to another by a lateral displacement of only 8 μm. The device is suitable for applications where the solution environment around a microscopic or nanoscopic sensor needs to be changed multiple times, i.e., in order to build layered structures, for obtaining binding isotherms, and kinetic information, for example, on ion channels, enzymes, and receptors as well as in applications where different loci on an object need to be exposed to different environments or where complex solution environments need to be created for studies of interfacial chemistry between two streaming layers.
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| 22. |
- Onoue, Y., et al.
(författare)
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A giant liposome for single-molecule observation of conformational changes in membrane proteins
- 2009
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Ingår i: Biochimica et Biophysica Acta - Biomembranes. - : Elsevier BV. - 1879-2642 .- 0005-2736. ; 1788:6, s. 1332-1340
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Tidskriftsartikel (refereegranskat)abstract
- We present an experimental system that allows visualization of conformational changes in membrane proteins at the single-molecule level. The target membrane protein is reconstituted in a giant liposome for independent control of the aqueous environments on the two sides of the membrane. For direct observation of conformational changes, an extra-liposomal site(s) of the target protein is bound to a glass surface, and a probe that is easily visible under a microscope, such as a micron-sized plastic bead, is attached to another site on the intra-liposomal side. A conformational change, or an angular motion in the tiny protein molecule, would manifest as a visible motion of the probe. The attachment of the protein on the glass surface also immobilizes the liposome, greatly facilitating its manipulation such as the probe injection. As a model system, we reconstituted ATP synthase (FOF1) in liposomes tens of mu m in size, attached the protein specifically to a glass surface, and demonstrated its ATP-driven rotation in the membrane through the motion of a submicron bead. (c) 2009 Elsevier B.V. All rights reserved.
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| 23. |
- Orwoll, Eric S., et al.
(författare)
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The Limited Clinical Utility of Testosterone, Estradiol, and Sex Hormone Binding Globulin Measurements in the Prediction of Fracture Risk and Bone Loss in Older Men
- 2017
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Ingår i: Journal of Bone and Mineral Research. - : WILEY. - 0884-0431 .- 1523-4681. ; 32:3, s. 633-640
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Tidskriftsartikel (refereegranskat)abstract
- Measurement of serum testosterone (T) levels is recommended in the evaluation of osteoporosis in older men and estradiol (E2) and sex hormone binding globulin (SHBG) levels are associated with the rate of bone loss and fractures, but the clinical utility of sex steroid and SHBG measurements for the evaluation of osteoporosis in men has not been examined. To evaluate whether measurements of T, E2, and/or SHBG are useful for the prediction of fracture risk or the rate of bone loss in older men, we analyzed longitudinal data from 5487 community-based men participating in the Osteoporotic Fractures in Men (MrOS) study in the United States, Sweden, and Hong Kong. Serum T, E2, and SHBG levels were assessed at baseline; incident fractures were self-reported at 4-month intervals with radiographic verification (US), or ascertained via national health records (Sweden, Hong Kong). Rate of bone loss was assessed by serial measures of hip bone mineral density (BMD). We used receiver operating characteristic (ROC) curves, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) to assess improvement in prediction. Mean age at baseline was 72 to 75 years and the prevalence of low T levels (<300 ng/dL) was 7.6% to 21.3% in the three cohorts. There were 619 incident major osteoporotic and 266 hip fractures during follow-up of approximately 10 years. Based on ROC curves, there were no improvements in fracture risk discrimination for any biochemical measure when added to models, including the Fracture Risk Assessment Tool (FRAX) with BMD. Although minor improvements in NRI were observed for the dichotomous parameters low bioavailable E2 (BioE2) (<11.4 pg/mL) and high SHBG(>59.1 nM), neither sex steroids nor SHBG provided clinically useful improvement in fracture risk discrimination. Similarly, they did not contribute to the prediction of BMD change. In conclusion, there is limited clinical utility of serum E2, T, and SHBG measures for the evaluation of osteoporosis risk in elderly men.
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| 24. |
- Paternoster, Lavinia, et al.
(författare)
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Genetic determinants of trabecular and cortical volumetric bone mineral densities and bone microstructure.
- 2013
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Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404 .- 1553-7390. ; 9:2
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Tidskriftsartikel (refereegranskat)abstract
- Most previous genetic epidemiology studies within the field of osteoporosis have focused on the genetics of the complex trait areal bone mineral density (aBMD), not being able to differentiate genetic determinants of cortical volumetric BMD (vBMD), trabecular vBMD, and bone microstructural traits. The objective of this study was to separately identify genetic determinants of these bone traits as analysed by peripheral quantitative computed tomography (pQCT). Separate GWA meta-analyses for cortical and trabecular vBMDs were performed. The cortical vBMD GWA meta-analysis (n=5,878) followed by replication (n=1,052) identified genetic variants in four separate loci reaching genome-wide significance (RANKL, rs1021188, p=3.6×10⁻¹⁴; LOC285735, rs271170, p=2.7×10⁻¹²; OPG, rs7839059, p=1.2×10⁻¹⁰; and ESR1/C6orf97, rs6909279, p=1.1×10⁻⁹). The trabecular vBMD GWA meta-analysis (n=2,500) followed by replication (n=1,022) identified one locus reaching genome-wide significance (FMN2/GREM2, rs9287237, p=1.9×10⁻⁹). High-resolution pQCT analyses, giving information about bone microstructure, were available in a subset of the GOOD cohort (n=729). rs1021188 was significantly associated with cortical porosity while rs9287237 was significantly associated with trabecular bone fraction. The genetic variant in the FMN2/GREM2 locus was associated with fracture risk in the MrOS Sweden cohort (HR per extra T allele 0.75, 95% confidence interval 0.60-0.93) and GREM2 expression in human osteoblasts. In conclusion, five genetic loci associated with trabecular or cortical vBMD were identified. Two of these (FMN2/GREM2 and LOC285735) are novel bone-related loci, while the other three have previously been reported to be associated with aBMD. The genetic variants associated with cortical and trabecular bone parameters differed, underscoring the complexity of the genetics of bone parameters. We propose that a genetic variant in the RANKL locus influences cortical vBMD, at least partly, via effects on cortical porosity, and that a genetic variant in the FMN2/GREM2 locus influences GREM2 expression in osteoblasts and thereby trabecular number and thickness as well as fracture risk.
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| 25. |
- Perrichon, Adrien, 1988, et al.
(författare)
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Local structure and vibrational dynamics of proton conducting Ba2In2O5(H2O)x
- 2019
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Ingår i: Journal of Materials Chemistry A. - : Royal Society of Chemistry (RSC). - 2050-7488 .- 2050-7496. ; 7:29, s. 17626-17636
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Tidskriftsartikel (refereegranskat)abstract
- We study the local structure and vibrational dynamics of the brownmillerite-based proton conductors Ba2In2O5(H2O)x, with x = 0.30, 0.76, and 0.92, using infrared spectroscopy, inelastic neutron scattering and ab initio molecular dynamics simulations. Ba2In2O5(H2O)x is found to exhibit two main types of proton sites, H(1) and H(2). The H(1) site is characterised by the coexistence of two intra-octahedral hydrogen-bond geometries, whereas the H(2) site is characterised by inter-octahedral hydrogen bonding. While the strength of the hydrogen bonding is similar for the majority of protons in the two proton sites, ≈10% of the H(2) protons forms unusually strong hydrogen bonds due to local proton environments characterised by an unusually short oxygen-oxygen separation distance of ≈2.6 Å. These local proton environments are manifested as two O-H stretch bands in the infrared absorbance spectra, at 255 and 290 meV, respectively. These O-H stretch bands are as well observed in the related class of In-doped perovskite-type oxides, BaInyZr1-yO3-y/2 (0.25 ≤ y ≤ 0.75), suggesting that these perovskites may display brownmillerite-like distortions on a local length scale. In effect, these results point towards a clustering of the In atoms in these perovskite materials. Further, the infrared spectra of Ba2In2O5(H2O)x show a minor evolution as a function of x, because the protons tend to segregate into oxygen-rich hydrogen-rich domains upon dehydration. This points towards a highly anisotropic proton conduction mechanism in partially hydrated phases. This insight motivates efforts to identify ways to avoid phase separation, perhaps by suitable cation substitutions, as a route to accommodate high proton conductivity.
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| 26. |
- Pihl, Johan, 1975, et al.
(författare)
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Microfluidic gradient-generating device for pharmacological profiling
- 2005
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Ingår i: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 77:13, s. 3897-3903
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Tidskriftsartikel (refereegranskat)abstract
- We describe an on-chip microfluidic gradient-generating device that generates concentration gradients spanning nearly 5 orders of magnitude starting from a single concentration. The exiting stream of drugs held at different concentrations remains laminar in a recording chamber and can be presented as 24 discrete solutions to a cell-based sensor. The high-performance characteristics of the device are demonstrated by pharmacological screening of voltage-gated K + channels (hERG) and ligand-gated GABAA receptors using scanning-probe patch-clamp measurements. Multiple data point dose-response curves and IC 50 and EC 50 values were rapidly obtained, typically in less than 30 min, through its combined functionality of gradient generation and open-volume laminar flow. The device facilitates rapid pharmacological profiling of ion channel and GPCR effectors and enables the acquisition of large numbers of data points with minute sample consumption and handling. © 2005 American Chemical Society.
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| 27. |
- Sandberg, David, 1980, et al.
(författare)
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The Characteristics of Sleepiness During Real Driving at Night - A Study of Driving Performance, Physiology and Subjective Experience
- 2011
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Ingår i: Sleep. - 1550-9109 .- 0161-8105. ; 34:10, s. 1317-1325
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Tidskriftsartikel (refereegranskat)abstract
- Study Objectives: Most studies of sleepy driving have been carried out in driving simulators. A few studies of real driving are available, but these have used only a few sleepiness indicators. The purpose of the present study was to characterize sleepiness in several indicators during real driving at night, compared with daytime driving. Design: Participants drove 55 km (at 90km/h) on a 9-m-wide rural highway in southern Sweden. Daytime driving started at 09: 00 or 11: 00 (2 groups) and night driving at 01: 00 or 03: 00 (balanced design). Setting: Instrumented car on a real road in normal traffic. Participants: Eighteen participants drawn from the local driving license register. Interventions: Daytime and nighttime drives. Measurement and Results: The vehicle was an instrumented car with video monitoring of the edge of the road and recording of the lateral position and speed. Electroencephalography and electrooculography were recorded, together with ratings of sleepiness every 5 minutes. Pronounced effects of night driving were seen for subjective sleepiness, electroencephalographic indicators of sleepiness, blink duration, and speed. Also, time on task showed significant effects for subjective sleepiness, blink duration, lane position, and speed. Sleepiness was highest toward the end of the nighttime drive. Night driving caused a leftward shift in lateral position and a reduction of speed. The latter two findings, as well as the overall pattern of sleepiness indicators, provide new insights into the effects of night driving. Conclusion: Night driving is associated with high levels of subjective, electrophysiologic, and behavioral sleepiness.
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| 28. |
- Sott, Kristin, 1974, et al.
(författare)
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Micropipet Writing Technique for Production of Two-Dimensional Lipid Bilayer Nanotube-Vesicle Networks on Functionalized and Patterned Surfaces
- 2003
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Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 19:9, s. 3904-3910
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Tidskriftsartikel (refereegranskat)abstract
- We present a micropipet-assisted writing technique for formation of two-dimensional networks of phospholipid vesicles and nanotubes on functionalized and patterned substrates. The substrates are patterned with vesicle-adhesive circular spots (5-7.5 µm in diameter) consisting of a basal layer of biotin on gold and an apical coating of NeutrAvidin in a sandwich manner. The area surrounding the adhesive spots is coated with a phosphatidylcholine bilayer membrane, preventing protein and liposome adhesion. Networks were formed by aspirating a biotin-functionalized giant unilamellar or multilamellar liposome (5-50 µm in diameter) into a ~3 µm inner diameter borosilicate glass micropipet. By using a pressurized-air microejection system, a portion of the liposome is then ejected back into the solution while forming a first vesicle ~3 µm in diameter. This vesicle is placed on an adhesive spot. When the micropipet is moved, a nanotube connection is formed from the first vesicle and is pulled to the next adhesive spot where a second vesicle is ejected. This procedure can then be repeated until the lipid material is consumed in the pipet. The method allows for formation of networks with a large number of nodes and vertexes with well-defined geometry and surface adhesion, and represents a first step toward very large scale integration of nanotube-vesicle networks in, for example, nanofluidic applications.
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| 29. |
- Teumer, A., et al.
(författare)
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Genomewide meta-analysis identifies loci associated with IGF-I and IGFBP-3 levels with impact on age-related traits
- 2016
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Ingår i: Aging Cell. - : Wiley. - 1474-9718 .- 1474-9726. ; 15:5, s. 811-824
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Tidskriftsartikel (refereegranskat)abstract
- The growth hormone/insulin-like growth factor (IGF) axis can be manipulated in animal models to promote longevity, and IGF-related proteins including IGF-I and IGF-binding protein-3 (IGFBP-3) have also been implicated in risk of human diseases including cardiovascular diseases, diabetes, and cancer. Through genomewide association study of up to 30884 adults of European ancestry from 21 studies, we confirmed and extended the list of previously identified loci associated with circulating IGF-I and IGFBP-3 concentrations (IGF1, IGFBP3, GCKR, TNS3, GHSR, FOXO3, ASXL2, NUBP2/IGFALS, SORCS2, and CELSR2). Significant sex interactions, which were characterized by different genotype–phenotype associations between men and women, were found only for associations of IGFBP-3 concentrations with SNPs at the loci IGFBP3 and SORCS2. Analyses of SNPs, gene expression, and protein levels suggested that interplay between IGFBP3 and genes within the NUBP2 locus (IGFALS and HAGH) may affect circulating IGF-I and IGFBP-3 concentrations. The IGF-I-decreasing allele of SNP rs934073, which is an eQTL of ASXL2, was associated with lower adiposity and higher likelihood of survival beyond 90years. The known longevity-associated variant rs2153960 (FOXO3) was observed to be a genomewide significant SNP for IGF-I concentrations. Bioinformatics analysis suggested enrichment of putative regulatory elements among these IGF-I- and IGFBP-3-associated loci, particularly of rs646776 at CELSR2. In conclusion, this study identified several loci associated with circulating IGF-I and IGFBP-3 concentrations and provides clues to the potential role of the IGF axis in mediating effects of known (FOXO3) and novel (ASXL2) longevity-associated loci. © 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.
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| 30. |
- Vandenput, Liesbeth, 1974, et al.
(författare)
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Low Testosterone, but Not Estradiol, Is Associated With Incident Falls in Older Men: The International MrOS Study
- 2017
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 32:6, s. 1174-1181
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Tidskriftsartikel (refereegranskat)abstract
- Fracture risk is determined by bone strength and the risk of falls. The relationship between serum sex steroids and bone strength parameters in men is well known, whereas the predictive value of sex steroids for falls is less studied. The aim of this study was to assess the associations between serum testosterone (T) and estradiol (E2) and the likelihood of falls. Older men (aged > 65 years) from the United States (n = 1919), Sweden (n = 2495), and Hong Kong (n = 1469) participating in the Osteoporotic Fractures in Men Study had baseline T and E2 analyzed by mass spectrometry. Bioavailable (Bio) levels were calculated using mass action equations. Incident falls were ascertained every 4 months during a mean follow-up of 5.7 years. Associations between sex steroids and falls were estimated by generalized estimating equations. Fall rate was highest in the US and lowest in Hong Kong (US 0.50, Sweden 0.31, Hong Kong 0.12 fall reports/person/year). In the combined cohort of 5883 men, total T (odds ratio [OR] per SD increase = 0.88, 95% confidence interval [CI] 0.86-0.91) and BioT (OR = 0.86, 95% CI 0.83-0.88) were associated with incident falls in models adjusted for age and prevalent falls. These associations were only slightly attenuated after simultaneous adjustment for physical performance variables (total T: OR = 0.94, 95% CI 0.91-0.96; BioT: OR = 0.91, 95% CI 0.89-0.94). E2, BioE2, and sex hormone-binding globulin (SHBG) were not significantly associated with falls. Analyses in the individual cohorts showed that both total T and BioT were associated with falls in MrOS US and Sweden. No association was found in MrOS Hong Kong, and this may be attributable to environmental factors rather than ethnic differences because total T and BioT predicted falls in MrOS US Asians. In conclusion, low total T and BioT levels, but not E2 or SHBG, are associated with increased falls in older men. (C) 2017 American Society for Bone and Mineral Research.
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| 31. |
- Wang, Z., et al.
(författare)
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Genome-wide association analyses of physical activity and sedentary behavior provide insights into underlying mechanisms and roles in disease prevention
- 2022
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 54:9, s. 1332-1344
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Tidskriftsartikel (refereegranskat)abstract
- Although physical activity and sedentary behavior are moderately heritable, little is known about the mechanisms that influence these traits. Combining data for up to 703,901 individuals from 51 studies in a multi-ancestry meta-analysis of genome-wide association studies yields 99 loci that associate with self-reported moderate-to-vigorous intensity physical activity during leisure time (MVPA), leisure screen time (LST) and/or sedentary behavior at work. Loci associated with LST are enriched for genes whose expression in skeletal muscle is altered by resistance training. A missense variant in ACTN3 makes the alpha-actinin-3 filaments more flexible, resulting in lower maximal force in isolated type IIA muscle fibers, and possibly protection from exercise-induced muscle damage. Finally, Mendelian randomization analyses show that beneficial effects of lower LST and higher MVPA on several risk factors and diseases are mediated or confounded by body mass index (BMI). Our results provide insights into physical activity mechanisms and its role in disease prevention. Multi-ancestry meta-analyses of genome-wide association studies for self-reported physical activity during leisure time, leisure screen time, sedentary commuting and sedentary behavior at work identify 99 loci associated with at least one of these traits.
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| 32. |
- Wennergren, Mattias, 1993, et al.
(författare)
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Swedish Child Health Services Register: a quality register for child health services and children's well-being.
- 2023
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Ingår i: BMJ paediatrics open. - : BMJ. - 2399-9772. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Swedish child health services (CHS) is a free-of-charge healthcare system that reaches almost all children under the age of 6. The aim for the CHS is to improve children's physical, psychological and social health by promoting health and development, preventing illness and detecting emerging problems early in the child's life. The services are defined in a national programme divided into three parts: universal interventions, targeted interventions and indicated interventions.The Swedish Child Health Services Register (BHVQ) is a national Quality Register developed in 2013. The register extracts data from the child's health record and automatically presents current data in real time. At present, the register includes 21 variables.We aim to describe data available in the BHVQ and the completeness of data in BHVQ across variables.Child-specific data were exported from the register, and data for children born in the regions were retrieved from Statistics Sweden to calculate coverage.The register includes over 110000 children born between 2011 and 2022 from 221 child healthcare centres in eight of Sweden's 21 regions. In seven of the eight regions, 100% of centres report data.The completeness of data differs between participating regions and birth cohorts. The average coverage for children born in 2021 is 71%.The BHVQ is a valuable resource for evaluating Child Health Services nationally, with high coverage for the youngest children. As a result of continuous improvement of the services, the possibility to follow the development of children's health in Sweden is possible through the register. When fully expanded, the register will be a natural and essential part of developing preventive services, improving healthcare for children below 6years of age and a tool for developing evidence-based child health interventions.
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| 33. |
- Zheng, Hou-Feng, et al.
(författare)
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WNT16 influences bone mineral density, Cortical bone thickness, bone strength, and Osteoporotic fracture risk
- 2012
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Ingår i: PLoS genetics. - SAN FRANCISCO, USA : PUBLIC LIBRARY SCIENCE. - 1553-7404. ; 8:7, s. e1002745-
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Tidskriftsartikel (refereegranskat)abstract
- We aimed to identify genetic variants associated with cortical bone thickness (CBT) and bone mineral density (BMD) by performing two separate genome-wide association study (GWAS) meta-analyses for CBT in 3 cohorts comprising 5,878 European subjects and for BMD in 5 cohorts comprising 5,672 individuals. We then assessed selected single-nucleotide polymorphisms (SNPs) for osteoporotic fracture in 2,023 cases and 3,740 controls. Association with CBT and forearm BMD was tested for ∼2.5 million SNPs in each cohort separately, and results were meta-analyzed using fixed effect meta-analysis. We identified a missense SNP (Thr>Ile; rs2707466) located in the WNT16 gene (7q31), associated with CBT (effect size of -0.11 standard deviations [SD] per C allele, P = 6.2×10(-9)). This SNP, as well as another nonsynonymous SNP rs2908004 (Gly>Arg), also had genome-wide significant association with forearm BMD (-0.14 SD per C allele, P = 2.3×10(-12), and -0.16 SD per G allele, P = 1.2×10(-15), respectively). Four genome-wide significant SNPs arising from BMD meta-analysis were tested for association with forearm fracture. SNP rs7776725 in FAM3C, a gene adjacent to WNT16, was associated with a genome-wide significant increased risk of forearm fracture (OR = 1.33, P = 7.3×10(-9)), with genome-wide suggestive signals from the two missense variants in WNT16 (rs2908004: OR = 1.22, P = 4.9×10(-6) and rs2707466: OR = 1.22, P = 7.2×10(-6)). We next generated a homozygous mouse with targeted disruption of Wnt16. Female Wnt16(-/-) mice had 27% (P<0.001) thinner cortical bones at the femur midshaft, and bone strength measures were reduced between 43%-61% (6.5×10(-13)
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