| 1. |
- Ghosheh, Nidal, et al.
(författare)
-
Comparative transcriptomics of hepatic differentiation of human pluripotent stem cells and adult human liver tissue
- 2017
-
Ingår i: Physiological Genomics. - : American Physiological Society. - 1094-8341 .- 1531-2267. ; 49:8, s. 430-446
-
Tidskriftsartikel (refereegranskat)abstract
- Hepatocytes derived from human pluripotent stem cells (hPSC-HEP) have the potential to replace presently used hepatocyte sources applied in liver disease treatment and models of drug discovery and development. Established hepatocyte differentiation protocols are effective and generate hepatocytes, which recapitulate some key features of their in vivo counterparts. However, generating mature hPSC-HEP remains a challenge. In this study, we applied transcriptomics to investigate the progress of in vitro hepatic differentiation of hPSCs at the developmental stages, definitive endoderm, hepatoblasts, early hPSC-HEP, and mature hPSC-HEP, to identify functional targets that enhance efficient hepatocyte differentiation. Using functional annotation, pathway and protein interaction network analyses, we observed the grouping of differentially expressed genes in specific clusters representing typical developmental stages of hepatic differentiation. In addition, we identified hub proteins and modules that were involved in the cell cycle process at early differentiation stages. We also identified hub proteins that differed in expression levels between hPSC-HEP and the liver tissue controls. Moreover, we identified a module of genes that were expressed at higher levels in the liver tissue samples than in the hPSC-HEP. Considering that hub proteins and modules generally are essential and have important roles in the protein-protein interactions, further investigation of these genes and their regulators may contribute to a better understanding of the differentiation process. This may suggest novel target pathways and molecules for improvement of hPSC-HEP functionality, having the potential to finally bring this technology to a wider use.
|
|
| 2. |
- Ghosheh, Nidal, et al.
(författare)
-
Highly Synchronized Expression of Lineage-Specific Genes during In Vitro Hepatic Differentiation of Human Pluripotent Stem Cell Lines
- 2016
-
Ingår i: Stem Cells International. - : Hindawi Limited. - 1687-966X .- 1687-9678.
-
Tidskriftsartikel (refereegranskat)abstract
- Human pluripotent stem cells- (hPSCs-) derived hepatocytes have the potential to replace many hepatic models in drug discovery and provide a cell source for regenerative medicine applications. However, the generation of fully functional hPSC-derived hepatocytes is still a challenge. Towards gaining better understanding of the differentiation and maturation process, we employed a standardized protocol to differentiate six hPSC lines into hepatocytes and investigated the synchronicity of the hPSC lines by applying RT-qPCR to assess the expression of lineage-specific genes (OCT4, NANOG, T, SOX17, CXCR4, CER1, HHEX, TBX3, PROX1, HNF6, AFP, HNF4a, KRT18, ALB, AAT, and CYP3A4) which serve as markers for different stages during liver development. The data was evaluated using correlation and clustering analysis, demonstrating that the expression of these markers is highly synchronized and correlated well across all cell lines. The analysis also revealed a distribution of the markers in groups reflecting the developmental stages of hepatocytes. Functional analysis of the differentiated cells further confirmed their hepatic phenotype. Taken together, these results demonstrate, on the molecular level, the highly synchronized differentiation pattern across multiple hPSC lines. Moreover, this study provides additional understanding for future efforts to improve the functionality of hPSC-derived hepatocytes and thereby increase the value of related models.
|
|
| 3. |
- Lestinsky, M., et al.
(författare)
-
Physics book: CRYRING@ESR
- 2016
-
Ingår i: European Physical Journal: Special Topics. - : Springer Science and Business Media LLC. - 1951-6401 .- 1951-6355. ; 225:5, s. 797-882
-
Forskningsöversikt (refereegranskat)abstract
- The exploration of the unique properties of stored and cooled beams of highly-charged ions as provided by heavy-ion storage rings has opened novel and fascinating research opportunities in the realm of atomic and nuclear physics research. Since the late 1980s, pioneering work has been performed at the CRYRING at Stockholm (Abrahamsson et al. 1993) and at the Test Storage Ring (TSR) at Heidelberg (Baumann et al. 1988). For the heaviest ions in the highest charge-states, a real quantum jump was achieved in the early 1990s by the commissioning of the Experimental Storage Ring (ESR) at GSI Helmholtzzentrum für Schwerionenforschung (GSI) in Darmstadt (Franzke 1987) where challenging experiments on the electron dynamics in the strong field regime as well as nuclear physics studies on exotic nuclei and at the borderline to atomic physics were performed. Meanwhile also at Lanzhou a heavy-ion storage ring has been taken in operation, exploiting the unique research opportunities in particular for medium-heavy ions and exotic nuclei (Xia et al. 2002).
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
- Asp, Margareta, professor, 1958-, et al.
(författare)
-
Physical mobility, physical activity, and obesity among elderly : findings from a large population-based Swedish survey
- 2017
-
Ingår i: Public Health. - : Elsevier B.V.. - 0033-3506 .- 1476-5616. ; 147, s. 84-91
-
Tidskriftsartikel (refereegranskat)abstract
- Objective To examine how physical activity and physical mobility are related to obesity in the elderly. Study design A cross-sectional study of 2558 men and women aged 65 years and older who participated in a population survey in 2012 was conducted in mid-Sweden with an overall response rate of 67%. Methods Obesity (body mass index ≥30 kg/m2) was based on self-reported weight and height, and physical activity and physical mobility on questionnaire data. Chi-squared test and multiple logistic regressions were used as statistical analyses. Results The overall prevalence of obesity was 19% in women and 15% in men and decreased after the age of 75 years. A strong association between both physical activity and obesity, and physical mobility and obesity was found. The odds for obesity were higher for impaired physical mobility (odds ratio [OR] 2.83, 95% confidence interval [CI] 2.14–3.75) than for physical inactivity (OR 1.63, 95% CI 1.28–2.08) when adjusted for gender, age, socio-economic status and fruit and vegetable intake. However, physical activity was associated with obesity only among elderly with physical mobility but not among those with impaired physical mobility. Conclusion It is important to focus on making it easier for elderly with physical mobility to become or stay physically active, whereas elderly with impaired physical mobility have a higher prevalence of obesity irrespective of physical activity.
|
|
| 7. |
|
|
| 8. |
- Azeez, Ahmed, et al.
(författare)
-
Low Cycle Fatigue Modelling of Steam Turbine Rotor Steel
- 2019
-
Ingår i: 9th International Conference Materials Structure & Micromechanics of Fracture (MSMF9). - : Elsevier. ; , s. 149-154, s. 149-154
-
Konferensbidrag (refereegranskat)abstract
- Materials in steam turbine rotors are subjected to cyclic loads at high temperature, causing cracks to initiate and grow. To allow for more flexible operation, accurate fatigue models for life prediction must not be overly conservative. In this study, fully reversed low cycle fatigue tests were performed on a turbine rotor steel called FB2. The tests were done isothermally, within temperature range of room temperature to 600 °C, under strain control with 0.8-1.2 % total strain range. Some tests included hold time to calibrate the short-time creep behaviour of the material. Different fatigue life models were constructed. The life curve in terms of stress amplitude was found unusable at 600 °C, while the life curve in terms of total strain or inelastic strain amplitudes displayed inconsistent behaviour at 500 °C. To construct better life model, the inelastic strain amplitudes were separated into plastic and creep components by modelling the deformation behaviour of the material, including creep. Based on strain range partitioning approach, the fatigue life depends on different damage mechanisms at different strain ranges. This allowed the formulation of life curves based on plasticity or creep domination, which showed creep domination at 600 °C, while at 500 °C, creep only dominates for higher strain range.
|
|
| 9. |
- Busse, Christian, et al.
(författare)
-
Evaluation of the crystallographic fatigue crack growth rate in a single-crystal nickel-base superalloy
- 2019
-
Ingår i: International Journal of Fatigue. - : ELSEVIER SCI LTD. - 0142-1123 .- 1879-3452. ; 127, s. 259-267
-
Tidskriftsartikel (refereegranskat)abstract
- Cracks in single-crystal nickel-base superalloys have been observed to switch cracking mode from Mode I to crystallographic cracking. The crack propagation rate is usually higher on the crystallographic planes compared to Mode I, which is important to account for in crack growth life predictions. In this paper, a method to evaluate the crystallographic fatigue crack growth rate, based on a previously developed crystallographic crack driving force parameter, is presented. The crystallographic crack growth rate was determined by evaluating heat tints on the fracture surfaces of the test specimens from the experiments. Complicated crack geometries including multiple crystallographic crack fronts were modelled in a three dimensional finite element context, The data points of the crystallographic fatigue crack growth rate collapse on a narrow scatter band for the crystallographic cracks indicating a correlation with the previously developed crystallographic crack driving force.
|
|
| 10. |
- Busse, Christian, 1989-, et al.
(författare)
-
Prediction of crystallographic cracking planes in single-crystal nickel-base superalloys
- 2018
-
Ingår i: Engineering Fracture Mechanics. - : Elsevier. - 0013-7944 .- 1873-7315. ; 196, s. 206-223
-
Tidskriftsartikel (refereegranskat)abstract
- The inherent anisotropy of single-crystal nickel-base superalloys brings many difficulties in terms of modelling, evaluation and prediction of fatigue crack growth. Two models to predict on which crystallographic plane cracking will occur is presented. The models are based on anisotropic stress intensity factors resolved on crystallographic slip planes calculated in a three-dimensional finite-element context. The developed models have been compared to experiments on two different test specimen geometries. The results show that a correct prediction of the crystallographic cracking plane can be achieved. This knowledge is of great interest for the industry and academia to better understand and predict crack growth in single-crystal materials.
|
|
