| 1. |
- Limburg, Karin E., et al.
(författare)
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In search of the dead zone : Use of otoliths for tracking fish exposure to hypoxia
- 2015
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Ingår i: Journal of Marine Systems. - : Elsevier BV. - 0924-7963 .- 1879-1573. ; 141, s. 167-178
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Tidskriftsartikel (refereegranskat)abstract
- Otolith chemistry is often useful for tracking provenance of fishes, as well as examining migration histories. Whereas elements such as strontium and barium correlate well with salinity and temperature, experiments that examine manganese uptake as a function of these parameters have found no such correlation. Instead, dissolved manganese is available as a redox product, and as such, is indicative of low-oxygen conditions. Here we present evidence for that mechanism in a range of habitats from marine to freshwater, across species, and also present ancillary proxies that support the mechanism as well. For example, iodine is redox-sensitive and varies inversely with Mn; and sulfur stable isotope ratios provide evidence of anoxic sulfate reduction in some circumstances. Further, S may be incorporated trophically whereas other elements appear to be taken up directly from water. This research suggests a potential means to identify individual fish exposure to hypoxia, over entire lifetimes. With further testing and understanding, in the future fish may be able to be used as "mobile monitors" of hypoxic conditions. (C) 2014 The Authors. Published by Elsevier B.V.
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| 2. |
- Brockmann, Sarah J., et al.
(författare)
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CHCHD10 mutations p.R15L and p.G66V cause motoneuron disease by haploinsufficiency
- 2018
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Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 27:4, s. 706-715
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Tidskriftsartikel (refereegranskat)abstract
- Mutations in the mitochondrially located protein CHCHD10 cause motoneuron disease by an unknown mechanism. In this study, we investigate the mutations p. R15L and p. G66V in comparison to wild-type CHCHD10 and the non-pathogenic variant p. P34S in vitro, in patient cells as well as in the vertebrate in vivo model zebrafish. We demonstrate a reduction of CHCHD10 protein levels in p. R15L and p. G66V mutant patient cells to approximately 50%. Quantitative real-time PCR revealed that expression of CHCHD10 p. R15L, but not of CHCHD10 p. G66V, is already abrogated at the mRNA level. Altered secondary structure and rapid protein degradation are observed with regard to the CHCHD10 p. G66V mutant. In contrast, no significant differences in expression, degradation rate or secondary structure of non-pathogenic CHCHD10 p. P34S are detected when compared with wild-type protein. Knockdown of CHCHD10 expression in zebrafish to about 50% causes motoneuron pathology, abnormal myofibrillar structure and motility deficits in vivo. Thus, our data show that the CHCHD10 mutations p. R15L and p. G66V cause motoneuron disease primarily based on haploinsufficiency of CHCHD10.
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| 3. |
- Dunlop, Malcolm G, et al.
(författare)
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Cumulative impact of 10 common genetic variants on colorectal cancer risk in 42,333 individuals from eight populations
- 2012
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Ingår i: Gut. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. - 1468-3288 .- 0017-5749.
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Colorectal cancer (CRC) has a substantial heritable component. Common genetic variation has been shown to contribute to CRC risk. A study was conducted in a large multi-population study to assess the feasibility of CRC risk prediction using common genetic variant data combined with other risk factors. A risk prediction model was built and applied to the Scottish population using available data. DESIGN: Nine populations of European descent were studied to develop and validate CRC risk prediction models. Binary logistic regression was used to assess the combined effect of age, gender, family history (FH) and genotypes at 10 susceptibility loci that individually only modestly influence CRC risk. Risk models were generated from case-control data incorporating genotypes alone (n=39 266) and in combination with gender, age and FH (n=11 324). Model discriminatory performance was assessed using 10-fold internal cross-validation and externally using 4187 independent samples. The 10-year absolute risk was estimated by modelling genotype and FH with age- and gender-specific population risks. RESULTS: The median number of risk alleles was greater in cases than controls (10 vs 9, p<2.2×10(-16)), confirmed in external validation sets (Sweden p=1.2×10(-6), Finland p=2×10(-5)). The mean per-allele increase in risk was 9% (OR 1.09; 95% CI 1.05 to 1.13). Discriminative performance was poor across the risk spectrum (area under curve for genotypes alone 0.57; area under curve for genotype/age/gender/FH 0.59). However, modelling genotype data, FH, age and gender with Scottish population data shows the practicalities of identifying a subgroup with >5% predicted 10-year absolute risk. CONCLUSION: Genotype data provide additional information that complements age, gender and FH as risk factors, but individualised genetic risk prediction is not currently feasible. Nonetheless, the modelling exercise suggests public health potential since it is possible to stratify the population into CRC risk categories, thereby informing targeted prevention and surveillance.
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| 4. |
- Moritz, Juliane, et al.
(författare)
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Electron beam powder bed fusion of γ‐titanium aluminide : Effect of processing parameters on part density, surface characteristics and aluminum content
- 2021
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Ingår i: Metals. - : MDPI. - 2075-4701. ; 11:7
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Tidskriftsartikel (refereegranskat)abstract
- Gamma titanium aluminides are very interesting for their use in high‐performance applications such as aircraft engines due to their low density, high stiffness and favorable hightemperature properties. However, the pronounced brittleness of these intermetallic alloys is a major challenge for their processing through conventional fabrication methods. Additive manufacturing by means of electron beam powder bed fusion (EB‐PBF) significantly improves the processability of titanium aluminides due to the high preheating temperatures and facilitates complex components. The objective of this study was to determine a suitable processing window for EB‐PBF of the TNM‐B1 alloy (Ti‐43.5Al‐4Nb‐1Mo‐0.1B), using an increased aluminum content in the powder raw material to compensate for evaporation losses during the process. Design of experiments was used to evaluate the effect of beam current, scan speed, focus offset, line offset and layer thickness on porosity. Top surface roughness was assessed through laser scanning confocal microscopy. Scanning electron microscopy, electron backscatter diffraction (EBSD) and energydispersive X‐ray spectroscopy (EDX) were used for microstructural investigation and to analyze aluminum loss depending on the volumetric energy density used in EB‐PBF. An optimized process parameter set for achieving part densities of 99.9% and smooth top surfaces was derived. The results regarding microstructures and aluminum evaporation suggest a solidification via the β‐phase.
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| 5. |
- Moritz, Juliane, et al.
(författare)
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Influence of Electron Beam Powder Bed Fusion Process Parameters at Constant Volumetric Energy Density on Surface Topography and Microstructural Homogeneity of a Titanium Aluminide Alloy
- 2023
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Ingår i: Advanced Engineering Materials. - : John Wiley & Sons. - 1438-1656 .- 1527-2648. ; 25:15
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Tidskriftsartikel (refereegranskat)abstract
- In powder bed fusion additive manufacturing, the volumetric energy density E V is a commonly used parameter to quantify process energy input. However, recent results question the suitability of E V as a design parameter, as varying the contributing parameters may yield different part properties. Herein, beam current, scan velocity, and line offset in electron beam powder bed fusion (PBF-EB) of the titanium aluminide alloy TNM–B1 are systematically varied while maintaining an overall constant E V. The samples are evaluated regarding surface morphology, relative density, microstructure, hardness, and aluminum loss due to evaporation. Moreover, the specimens are subjected to two different heat treatments to obtain fully lamellar (FL) and nearly lamellar (NLγ) microstructures, respectively. With a combination of low beam currents, low-to-intermediate scan velocities, and low line offsets, parts with even surfaces, relative densities above 99.9%, and homogeneous microstructures are achieved. On the other hand, especially high beam currents promote the formation of surface bulges and pronounced aluminum evaporation, resulting in inhomogeneous banded microstructures after heat treatment. The results demonstrate the importance of considering the individual parameters instead of E V in process optimization for PBF-EB.
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| 6. |
- Moritz, Juliane, et al.
(författare)
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Influence of Two-Step Heat Treatments on Microstructure and Mechanical Properties of a β-Solidifying Titanium Aluminide Alloy Fabricated via Electron Beam Powder Bed Fusion
- 2023
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Ingår i: Advanced Engineering Materials. - : John Wiley & Sons. - 1438-1656 .- 1527-2648. ; 25:2
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Tidskriftsartikel (refereegranskat)abstract
- Additive manufacturing technologies, particularly electron beam powder bed fusion (PBF-EB/M), are becoming increasingly important for the processing of intermetallic titanium aluminides. This study presents the effects of hot isostatic pressing (HIP) and subsequent two-step heat treatments on the microstructure and mechanical properties of the TNM-B1 alloy (Ti–43.5Al–4Nb–1Mo–0.1B) fabricated via PBF-EB/M. Adequate solution heat treatment temperatures allow the adjustment of fully lamellar (FL) and nearly lamellar (NL-β) microstructures. The specimens are characterized by optical microscopy and scanning electron microscopy (SEM), X-ray computed tomography (CT), X-ray diffraction (XRD), and electron backscatter diffraction (EBSD). The mechanical properties at ambient temperatures are evaluated via tensile testing and subsequent fractography. While lack-of-fusion defects are the main causes of failure in the as-built condition, the mechanical properties in the heat-treated conditions are predominantly controlled by the microstructure. The highest ultimate tensile strength is achieved after HIP due to the elimination of lack-of-fusion defects. The results reveal challenges originating from the PBF-EB/M process, for example, local variations in chemical composition due to aluminum evaporation, which in turn affect the microstructures after heat treatment. For designing suitable heat treatment strategies, particular attention should therefore be paid to the microstructural characteristics associated with additive manufacturing.
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| 7. |
- Moritz, Juliane, et al.
(författare)
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Locally Adapted Microstructures in an Additively Manufactured Titanium Aluminide Alloy Through Process Parameter Variation and Heat Treatment
- 2023
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Ingår i: Advanced Engineering Materials. - : John Wiley & Sons. - 1438-1656 .- 1527-2648. ; 25:2
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Tidskriftsartikel (refereegranskat)abstract
- Electron beam powder bed fusion (PBF-EB/M) has been attracting great research interest as a promising technology for additive manufacturing of titanium aluminide alloys. However, challenges often arise from the process-induced evaporation of aluminum, which is linked to the PBF-EB/M process parameters. This study applies different volumetric energy densities during PBF-EB/M processing to deliberately adjust the aluminum contents in additively manufactured Ti–43.5Al–4Nb–1Mo–0.1B (TNM-B1) samples. The specimens are subsequently subjected to hot isostatic pressing (HIP) and a two-step heat treatment. The influence of process parameter variation and heat treatments on microstructure and defect distribution are investigated using optical and scanning electron microscopy, as well as X-ray computed tomography (CT). Depending on the aluminum content, shifts in the phase transition temperatures can be identified via differential scanning calorimetry (DSC). It is confirmed that the microstructure after heat treatment is strongly linked to the PBF-EB/M parameters and the associated aluminum evaporation. The feasibility of producing locally adapted microstructures within one component through process parameter variation and subsequent heat treatment can be demonstrated. Thus, fully lamellar and nearly lamellar microstructures in two adjacent component areas can be adjusted, respectively.
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| 8. |
- Nyström, Helena, 1985-, et al.
(författare)
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Prognosis after intensive care for COPD exacerbation in relation to long-term oxygen therapy : a nationwide cohort study
- 2023
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Ingår i: COPD. - : Routledge. - 1541-2555 .- 1541-2563. ; 20:1, s. 64-70
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Tidskriftsartikel (refereegranskat)abstract
- Decisions to admit or refuse admission to intensive care for acute exacerbations of COPD (AECOPD) can be difficult, due to an uncertainty about prognosis. Few studies have evaluated outcomes after intensive care for AECOPD in patients with chronic respiratory failure requiring long-term oxygen therapy (LTOT). In this nationwide observational cohort study, we investigated survival after first-time admission for AECOPD in all patients aged ≥40 years admitted to Swedish intensive care units between January 2008 and December 2015, comparing patients with and without LTOT. Among the 4,648 patients enrolled in the study, 450 were on LTOT prior to inclusion. Respiratory support data was available for 2,631 patients; 73% of these were treated with noninvasive ventilation (NIV) only, 17% were treated with immediate invasive ventilation, and 10% were intubated after failed attempt with NIV. Compared to patients without LTOT, patients with LTOT had higher 30-day mortality (38% vs. 25%; p < 0.001) and one-year mortality (70% vs. 43%; p < 0.001). Multivariable logistic and Cox regression models adjusted for age, sex and SAPS3 score confirmed higher mortality in LTOT, odds ratio for 30-day mortality was 1.8 ([95% confidence interval] 1.5–2.3) and hazard ratio for one-year mortality was 1.8 (1.6–2.0). In summary, although need for LTOT is a negative prognostic marker for survival after AECOPD requiring intensive care, a majority of patients with LTOT survived the AECOPD and 30% were alive after one year.
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| 9. |
- Plötner, Björn, et al.
(författare)
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Chlorosis caused by two recessively interacting genes reveals a role of RNA helicase in hybrid breakdown in Arabidopsis thaliana
- 2017
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Ingår i: The Plant Journal. - : Wiley. - 0960-7412 .- 1365-313X. ; 91:2, s. 251-262
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Tidskriftsartikel (refereegranskat)abstract
- Hybrids often differ in fitness from their parents. They may be superior, translating into hybrid vigour or heterosis, but they may also be markedly inferior, because of hybrid weakness or incompatibility. The underlying genetic causes for the latter can often be traced back to genes that evolve rapidly because of sexual or host-pathogen conflicts. Hybrid weakness may manifest itself only in later generations, in a phenomenon called hybrid breakdown. We have characterized a case of hybrid breakdown among two Arabidopsis thaliana accessions, Shahdara (Sha, Tajikistan) and Lövvik-5 (Lov-5, Northern Sweden). In addition to chlorosis, a fraction of the F2 plants have defects in leaf and embryo development, and reduced photosynthetic efficiency. Hybrid chlorosis is due to two major-effect loci, of which one, originating from Lov-5, appears to encode an RNA helicase (AtRH18). To examine the role of the chlorosis allele in the Lövvik area, in addition to eight accessions collected in 2009, we collected another 240 accessions from 15 collections sites, including Lövvik, from Northern Sweden in 2015. Genotyping revealed that Lövvik collection site is separated from the rest. Crosses between 109 accessions from this area and Sha revealed 85 cases of hybrid chlorosis, indicating that the chlorosis-causing allele is common in this area. These results suggest that hybrid breakdown alleles not only occur at rapidly evolving loci, but also at genes that code for conserved processes.
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