| 31. |
- Beaumont, Robin N, et al.
(författare)
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Genome-wide association study of offspring birth weight in 86,577 women identifies five novel loci and highlights maternal genetic effects that are independent of fetal genetics.
- 2018
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Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 1460-2083 .- 0964-6906. ; 27:4, s. 742-756
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) of birth weight have focused on fetal genetics, while relatively little is known about the role of maternal genetic variation. We aimed to identify maternal genetic variants associated with birth weight that could highlight potentially relevant maternal determinants of fetal growth. We meta-analysed data on up to 8.7 million SNPs in up to 86,577 women of European descent from the Early Growth Genetics (EGG) Consortium and the UK Biobank. We used structural equation modelling (SEM) and analyses of mother-child pairs to quantify the separate maternal and fetal genetic effects. Maternal SNPs at 10 loci (MTNR1B, HMGA2, SH2B3, KCNAB1, L3MBTL3, GCK, EBF1, TCF7L2, ACTL9, CYP3A7) were associated with offspring birth weight at P<5x10-8. In SEM analyses, at least 7 of the 10 associations were consistent with effects of the maternal genotype acting via the intrauterine environment, rather than via effects of shared alleles with the fetus. Variants, or correlated proxies, at many of the loci had been previously associated with adult traits, including fasting glucose (MTNR1B, GCK and TCF7L2) and sex hormone levels (CYP3A7), and one (EBF1) with gestational duration. The identified associations indicate genetic effects on maternal glucose, cytochrome P450 activity and gestational duration, and potentially on maternal blood pressure and immune function, are relevant for fetal growth. Further characterization of these associations in mechanistic and causal analyses will enhance understanding of the potentially modifiable maternal determinants of fetal growth, with the goal of reducing the morbidity and mortality associated with low and high birth weights.
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| 32. |
- Been, Frederic, et al.
(författare)
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Assessing geographical differences in illicit drug consumption-A comparison of results from epidemiological and wastewater data in Germany and Switzerland
- 2016
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Ingår i: Drug And Alcohol Dependence. - : Elsevier BV. - 0376-8716 .- 1879-0046. ; 161, s. 189-199
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Tidskriftsartikel (refereegranskat)abstract
- Background: Wastewater analysis is an innovative approach that allows monitoring illicit drug use at the community level. This study focused on investigating geographical differences in drug consumption by comparing epidemiological, crime and wastewater data. Methods: Wastewater samples were collected in 19 cities across Germany and Switzerland during one week, covering a population of approximately 8.1 million people. Self-report data and consumption offences for the investigated areas were used for comparison and to investigate differences between the indicators. Results: Good agreement between data sources was observed for cannabis and amphetamine-type stimulants, whereas substantial discrepancies were observed for cocaine. In Germany, an important distinction could be made between Berlin, Dortmund and Munich, where cocaine and particularly amphetamine were more prevalent, and Dresden, where methamphetamine consumption was clearly predominant. Cocaine consumption was relatively homogenous in the larger urban areas of Switzerland, although prevalence and offences data suggested a more heterogeneous picture. Conversely, marked regional differences in amphetamine and methamphetamine consumption could be highlighted. Conclusions: Combining the available data allowed for a better understanding of the geographical differences regarding prevalence, typology and amounts of substances consumed. For cannabis and amphetamine-type stimulants, the complementarity of survey, police and wastewater data could be highlighted, although notable differences could be identified when considering more stigmatised drugs (i.e. cocaine and heroin). Understanding illicit drug consumption at the national scale remains a difficult task, yet this research illustrates the added value of combining complementary data sources to obtain a more comprehensive and accurate picture of the situation.
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| 33. |
- Bender, P., et al.
(författare)
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Relating Magnetic Properties and High Hyperthermia Performance of Iron Oxide Nanoflowers
- 2018
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Ingår i: Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 122:5, s. 3068-3077
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Tidskriftsartikel (refereegranskat)abstract
- We investigated, in depth, the interrelations among structure, magnetic properties, relaxation dynamics and magnetic hyperthermia performance of magnetic nanoflowers. The nanoflowers are about 39 nm in size, and consist of densely packed iron oxide cores. They display a remanent magnetization, which we explain by the exchange coupling between the cores, but we observe indications for internal spin disorder. By polarized small-angle neutron scattering, we unambiguously confirm that, on average, the nanoflowers are preferentially magnetized along one direction. The extracted discrete relaxation time distribution of the colloidally dispersed particles indicates the presence of three distinct relaxation contributions. We can explain the two slower processes by Brownian and classical Néel relaxation, respectively. The additionally observed very fast relaxation contributions are attributed by us to the relaxation of disordered spins within the nanoflowers. Finally, we show that the intrinsic loss power (ILP, magnetic hyperthermia performance) of the nanoflowers measured in colloidal dispersion at high frequency is comparatively large and independent of the viscosity of the surrounding medium. This concurs with our assumption that the observed relaxation in the high frequency range is primarily a result of internal spin relaxation, and possibly connected to the disordered spins within the individual nanoflowers.
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| 34. |
- Bergamaschi, Peter, et al.
(författare)
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Inverse modelling of European CH4 emissions during 2006–2012 using different inverse models and reassessed atmospheric observations
- 2018
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Ingår i: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7324. ; 18:2, s. 901-920
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Tidskriftsartikel (refereegranskat)abstract
- We present inverse modelling (top down) estimates of European methane (CH4) emissions for 2006–2012 based on a new quality-controlled and harmonised in situ data set from 18 European atmospheric monitoring stations. We applied an ensemble of seven inverse models and performed four inversion experiments, investigating the impact of different sets of stations and the use of a priori information on emissions. The inverse models infer total CH4 emissions of 26.8 (20.2–29.7) Tg CH4 yr−1 (mean, 10th and 90th percentiles from all inversions) for the EU-28 for 2006–2012 from the four inversion experiments. For comparison, total anthropogenic CH4 emissions reported to UNFCCC (bottom up, based on statistical data and emissions factors) amount to only 21.3 Tg CH4 yr−1 (2006) to 18.8 Tg CH4 yr−1 (2012). A potential explanation for the higher range of top-down estimates compared to bottom-up inventories could be the contribution from natural sources, such as peatlands, wetlands, and wet soils. Based on seven different wetland inventories from the Wetland and Wetland CH4 Inter-comparison of Models Project (WETCHIMP), total wetland emissions of 4.3 (2.3–8.2) Tg CH4 yr−1 from the EU-28 are estimated. The hypothesis of significant natural emissions is supported by the finding that several inverse models yield significant seasonal cycles of derived CH4 emissions with maxima in summer, while anthropogenic CH4 emissions are assumed to have much lower seasonal variability. Taking into account the wetland emissions from the WETCHIMP ensemble, the top-down estimates are broadly consistent with the sum of anthropogenic and natural bottom-up inventories. However, the contribution of natural sources and their regional distribution remain rather uncertain. Furthermore, we investigate potential biases in the inverse models by comparison with regular aircraft profiles at four European sites and with vertical profiles obtained during the Infrastructure for Measurement of the European Carbon Cycle (IMECC) aircraft campaign. We present a novel approach to estimate the biases in the derived emissions, based on the comparison of simulated and measured enhancements of CH4 compared to the background, integrated over the entire boundary layer and over the lower troposphere. The estimated average regional biases range between −40 and 20 % at the aircraft profile sites in France, Hungary and Poland.
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| 35. |
- Brandau, Benedikt, et al.
(författare)
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Absorbance study of powder conditions for laser additive manufacturing
- 2022
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Ingår i: Materials & design. - : Elsevier. - 0264-1275 .- 1873-4197. ; 216
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Tidskriftsartikel (refereegranskat)abstract
- Absorbance is often used for simulations or validation of process parameters for powder-based laser materials processing. In this work, the absorbance of 39 metal powders for additive manufacturing is determined at 20 laser wavelengths. Different grain sizes and aging states for: steels, aluminum alloys, titanium alloys, Nitinol, high entropy alloy, chromium, copper, brass and iron ore were analyzed. For this purpose, the absorbance spectrum of the powders was determined via a dual-beam spectrometer in the range of λ = 330 - 1560 nm. At the laser wavelengths of λ = 450 nm, 633 nm and 650 nm, the absorbance averaged over all materials was found to increase by a factor of 2.4 up to 3.3 compared to the usual wavelength of λ = 1070 nm, with minimal variations in absorbance between materials. In the investigation of the aged or used powders, a loss of absorbance was detectable. Almost no changes from the point of view of processing aged and new AlSi10Mg powders, is expected for laser sources with λ = 450 nm. The resulting measurements provide a good basis for process parameters for a variety of laser wavelengths and materials, as well as a data set for improved absorbance simulations.
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| 36. |
- Brueckner, Frank, et al.
(författare)
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Enhanced manufacturing possibilities using multi-materials in laser metal deposition
- 2018
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Ingår i: Journal of laser applications. - : American Institute of Physics (AIP). - 1042-346X .- 1938-1387. ; 26:2, s. 10-12
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Tidskriftsartikel (refereegranskat)abstract
- Additive manufacturing (AM) addresses various benefits as the buildup of complex shaped parts, the possibility of functional integration, reduced lead times or the use of difficult machinable materials compared to conventional manufacturing possibilities. Beside these advantages, the use of more than one material in a component would strongly increase the field of applications in typical AM branches as energy, aerospace, or medical technology. By means of multi-material buildups, cost-intensive alloys could be only used in high-loaded areas of the part, whereas the remaining part could be fabricated with cheaper compositions. The selection of combined materials strongly depends on the requested thermophysical but also mechanical properties. Within this contribution, examples (e.g., used in the turbine business) show how alloys can be arranged to fit together, e.g., in terms of a well-chosen coefficient of thermal expansion. As can be seen in nature, the multi-material usage can be characterized by sharp intersections from one material to the other (e.g., in case of a thin corrosion protection), but also by graded structures enabling a smoother material transition (e.g., in case of dissimilar materials which are joined together without defects). The latter is shown for an example from aerospace within this paper. Another possibility is the simultaneous placement of several materials, e.g., hard carbide particles placed in a more ductile matrix composition. These particles can be varied in size (e.g., TiC versus WC). Also the ratio between carbides and matrix alloy can be adjusted depending on its application. Especially, nozzle-based free form fabrication technologies, e.g., laser metal deposition, enable the utilization of more than one material. Within this contribution, possibilities to feed more than one filler material are demonstrated. In addition, results of multi-material processes are shown. Finally, this work focuses on different (potential) applications, mainly on power generation, but also for medical technology or wear resistant components.
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| 37. |
- Brueckner, Frank, et al.
(författare)
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Fabrication of metallic multi-material components using Laser Metal Deposition
- 2017
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Ingår i: Solid Freeform Fabrication 2017. - : The University of Texas at Austin. ; , s. 2530-2538
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Meanwhile, Laser Metal Deposition (LMD) is a well-known Additive Manufacturing technology used in various industrial branches as energy, tooling or aerospace. It can be used for the fabrication of new components but also repair applications. So far, volume build-ups were mostly carried out with one single material only. However, loading conditions may strongly vary and, hence, the use of more than one material in a component would yield major benefits. By means of multi-material build-ups, cost-intensive alloys could be used in highly-loaded areas of the part, whereas the remaining part could be fabricated with cheaper compositions. The selection of combined materials strongly depends on the requested thermo-physical and mechanical properties. Within this contribution, possibilities of material combinations by LMD and selected examples of beneficial multi-material use are presented.
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| 38. |
- Brunner, Fabian J., et al.
(författare)
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Application of non-HDL cholesterol for population-based cardiovascular risk stratification : results from the Multinational Cardiovascular Risk Consortium
- 2019
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Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 394:10215, s. 2173-2183
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Tidskriftsartikel (refereegranskat)abstract
- Background: The relevance of blood lipid concentrations to long-term incidence of cardiovascular disease and the relevance of lipid-lowering therapy for cardiovascular disease outcomes is unclear. We investigated the cardiovascular disease risk associated with the full spectrum of bloodstream non-HDL cholesterol concentrations. We also created an easy-to-use tool to estimate the long-term probabilities for a cardiovascular disease event associated with non-HDL cholesterol and modelled its risk reduction by lipid-lowering treatment.Methods: In this risk-evaluation and risk-modelling study, we used Multinational Cardiovascular Risk Consortium data from 19 countries across Europe, Australia, and North America. Individuals without prevalent cardiovascular disease at baseline and with robust available data on cardiovascular disease outcomes were included. The primary composite endpoint of atherosclerotic cardiovascular disease was defined as the occurrence of the coronary heart disease event or ischaemic stroke. Sex-specific multivariable analyses were computed using non-HDL cholesterol categories according to the European guideline thresholds, adjusted for age, sex, cohort, and classical modifiable cardiovascular risk factors. In a derivation and validation design, we created a tool to estimate the probabilities of a cardiovascular disease event by the age of 75 years, dependent on age, sex, and risk factors, and the associated modelled risk reduction, assuming a 50% reduction of non-HDL cholesterol.Findings: Of the 524 444 individuals in the 44 cohorts in the Consortium database, we identified 398 846 individuals belonging to 38 cohorts (184 055 [48·7%] women; median age 51·0 years [IQR 40·7–59·7]). 199 415 individuals were included in the derivation cohort (91 786 [48·4%] women) and 199 431 (92 269 [49·1%] women) in the validation cohort. During a maximum follow-up of 43·6 years (median 13·5 years, IQR 7·0–20·1), 54 542 cardiovascular endpoints occurred. Incidence curve analyses showed progressively higher 30-year cardiovascular disease event-rates for increasing non-HDL cholesterol categories (from 7·7% for non-HDL cholesterol <2·6 mmol/L to 33·7% for ≥5·7 mmol/L in women and from 12·8% to 43·6% in men; p<0·0001). Multivariable adjusted Cox models with non-HDL cholesterol lower than 2·6 mmol/L as reference showed an increase in the association between non-HDL cholesterol concentration and cardiovascular disease for both sexes (from hazard ratio 1·1, 95% CI 1·0–1·3 for non-HDL cholesterol 2·6 to <3·7 mmol/L to 1·9, 1·6–2·2 for ≥5·7 mmol/L in women and from 1·1, 1·0–1·3 to 2·3, 2·0–2·5 in men). The derived tool allowed the estimation of cardiovascular disease event probabilities specific for non-HDL cholesterol with high comparability between the derivation and validation cohorts as reflected by smooth calibration curves analyses and a root mean square error lower than 1% for the estimated probabilities of cardiovascular disease. A 50% reduction of non-HDL cholesterol concentrations was associated with reduced risk of a cardiovascular disease event by the age of 75 years, and this risk reduction was greater the earlier cholesterol concentrations were reduced.Interpretation: Non-HDL cholesterol concentrations in blood are strongly associated with long-term risk of atherosclerotic cardiovascular disease. We provide a simple tool for individual long-term risk assessment and the potential benefit of early lipid-lowering intervention. These data could be useful for physician–patient communication about primary prevention strategies.
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| 39. |
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| 40. |
- Caldararu, Octav, et al.
(författare)
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Binding free energies in the SAMPL5 octa-acid host–guest challenge calculated with DFT-D3 and CCSD(T)
- 2017
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Ingår i: Journal of Computer-Aided Molecular Design. - : Springer Science and Business Media LLC. - 0920-654X .- 1573-4951. ; 31:1, s. 87-106
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Tidskriftsartikel (refereegranskat)abstract
- We have tried to calculate the free energy for the binding of six small ligands to two variants of the octa-acid deep cavitand host in the SAMPL5 blind challenge. We employed structures minimised with dispersion-corrected density-functional theory with small basis sets and energies were calculated using large basis sets. Solvation energies were calculated with continuum methods and thermostatistical corrections were obtained from frequencies calculated at the HF-3c level. Care was taken to minimise the effects of the flexibility of the host by keeping the complexes as symmetric and similar as possible. In some calculations, the large net charge of the host was reduced by removing the propionate and benzoate groups. In addition, the effect of a restricted molecular dynamics sampling of structures was tested. Finally, we tried to improve the energies by using the DLPNO–CCSD(T) approach. Unfortunately, results of quite poor quality were obtained, with no correlation to the experimental data, systematically too positive affinities (by ~50 kJ/mol) and a mean absolute error (after removal of the systematic error) of 11–16 kJ/mol. DLPNO–CCSD(T) did not improve the results, so the accuracy is not limited by the energy function. Instead, four likely sources of errors were identified: first, the minimised structures were often incorrect, owing to the omission of explicit solvent. They could be partly improved by performing the minimisations in a continuum solvent with four water molecules around the charged groups of the ligands. Second, some ligands could bind in several different conformations, requiring sampling of reasonable structures. Third, there is an indication the continuum-solvation model has problems to accurately describe the binding of both the negatively and positively charged guest molecules. Fourth, different methods to calculate the thermostatistical corrections gave results that differed by up to 30 kJ/mol and there is an indication that HF-3c overestimates the entropy term. In conclusion, it is a challenge to calculate binding affinities for this octa-acid system with quantum–mechanical methods.
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