| 1. |
- Fellinger, Joris, et al.
(författare)
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Tungsten based divertor development for Wendelstein 7-X
- 2023
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Ingår i: Nuclear Materials and Energy. - 2352-1791. ; 37
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Tidskriftsartikel (refereegranskat)abstract
- Wendelstein 7-X, the world’s largest superconducting stellarator in Greifswald (Germany), started plasma experiments with a water-cooled plasma-facing wall in 2022, allowing for long pulse operation. In parallel, a project was launched in 2021 to develop a W based divertor, replacing the current CFC divertor, to demonstrate plasma performance of a stellarator with a reactor relevant plasma facing materials with low tritium retention. The project consists of two tasks: Based on experience from the previous experimental campaigns and improved physics modelling, the geometry of the plasma-facing surface of the divertor and baffles is optimized to prevent overloads and to improve exhaust. In parallel, the manufacturing technology for a W based target module is qualified. This paper gives a status update of project. It focusses on the conceptual design of a W based target module, the manufacturing technology and its qualification, which is conducted in the framework of the EUROfusion funded WPDIV program. A flat tile design in which a target module is made of a single target element is pursued. The technology must allow for moderate curvatures of the plasma-facing surface to follow the magnetic field lines. The target element is designed for steady state heat loads of 10 MW/m2 (as for the CFC divertor). Target modules of a similar size and weight as for the CFC divertor are assumed (approx. < 0.25 m2 and < 60 kg) using the existing water cooling infrastructure providing 5 l/s and roughly maximum 15 bar pressure drop per module. The main technology under qualification is based on a CuCrZr heat sink made either by additive manufacturing using laser powder bed fusion (LPBF) or by uniaxial diffusion welding of pre-machined forged CuCrZr plates. After heat treatment, the plasma-facing side of the heat sink is covered by W or if feasible by the more ductile WNiFe, preferably by coating or alternatively by hot isostatic pressing W based tiles with a soft OFE-Cu interlayer. Last step is a final machining of the plasma-exposed surface and the interfaces to the water supply lines and supports to correct manufacturing deformations.
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| 2. |
- Herling, L., et al.
(författare)
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Automated analysis of fetal cardiac function using color tissue Doppler imaging
- 2018
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Ingår i: Ultrasound in Obstetrics and Gynecology. - : Wiley. - 0960-7692 .- 1469-0705. ; 52:5, s. 599-608
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Tidskriftsartikel (refereegranskat)abstract
- Objective To evaluate the feasibility of automated analysis of fetal myocardial velocity recordings obtained by color tissue Doppler imaging (cTDI). Methods This was a prospective cross-sectional observational study of 107 singleton pregnancies >= 41 weeks of gestation. Myocardial velocity recordings were obtained by cTDI in a long-axis four-chamber view of the fetal heart. Regions of interest were placed in the septum and the right (RV) and left (LV) ventricular walls at the level of the atrioventricular plane. Peak myocardial velocities and mechanical cardiac time intervals were measured both manually and by an automated algorithm and agreement between the two methods was evaluated. Results In total, 321 myocardial velocity traces were analyzed using each method. It was possible to analyze all velocity traces obtained from the LV, RV and septal walls with the automated algorithm, and myocardial velocities and cardiac mechanical time intervals could be measured in 96% of all traces. The same results were obtained when the algorithm was run repeatedly. The myocardial velocities measured using the automated method correlated significantly with those measured manually. The agreement between methods was not consistent and some cTDI parameters had considerable bias and poor precision. Conclusions Automated analysis of myocardial velocity recordings obtained by cTDI was feasible, suggesting that this technique could simplify and facilitate the use of cTDI in the evaluation of fetal cardiac function, both in research and in clinical practice.
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| 3. |
- Herling, L., et al.
(författare)
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Automated analysis of fetal cardiac function using color tissue Doppler imaging in second half of normal pregnancy
- 2019
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Ingår i: Ultrasound in Obstetrics and Gynecology. - : WILEY. - 0960-7692 .- 1469-0705. ; 53:3, s. 348-357
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Color tissue Doppler imaging (cTDI) is a promising tool for the assessment of fetal cardiac function. However, the analysis of myocardial velocity traces is cumbersome and time-consuming, limiting its application in clinical practice. The aim of this study was to evaluate fetal cardiac function during the second half of pregnancy and to develop reference ranges using an automated method to analyze cTDI recordings from a cardiac four-chamber view. Methods This was a cross-sectional study including 201 normal singleton pregnancies between 18 and 42weeks of gestation. During fetal echocardiography, a four-chamber view of the heart was visualized and cTDI was performed. Regions of interest were positioned at the level of the atrioventricular plane in the left ventricular (LV), right ventricular (RV) and septal walls of the fetal heart, to obtain myocardial velocity traces that were analyzed offline using the automated algorithm. Peak myocardial velocities during atrial contraction (Am), ventricular ejection (Sm) and rapid ventricular filling, i. e. early diastole (Em), as well as the Em/Am ratio, mechanical cardiac time intervals and myocardial performance index (cMPI) were evaluated, and gestational age-specific reference ranges were constructed. Results At 18 weeks of gestation, the peak myocardial velocities, presented as fitted mean with 95% CI, were: LV Am, 3.39 (3.09-3.70) cm/s; LV Sm, 1.62 (1.46-1.79) cm/s; LV Em, 1.95 (1.75-2.15) cm/s; septal Am, 3.07 (2.80-3.36) cm/s; septal Sm, 1.93 (1.81-2.06) cm/s; septal Em, 2.57 (2.32-2.84) cm/s; RV Am, 4.89 (4.59-5.20) cm/s; RV Sm, 2.31 (2.16-2.46) cm/s; and RV Em, 2.94 (2.69-3.21) cm/s. At 42weeks of gestation, the peak myocardial velocities had increased to: LV Am, 4.25 (3.87-4.65) cm/s; LV Sm, 3.53 (3.19-3.89) cm/s; LV Em, 4.55 (4.18-4.94) cm/s; septal Am, 4.49 (4.17-4.82) cm/s; septal Sm, 3.36 (3.17-3.55) cm/s; septal Em, 3.76 (3.51-4.03) cm/s; RV Am, 6.52 (6.09-6.96) cm/s; RV Sm, 4.95 (4.59-5.32) cm/s; and RV Em, 5.42 (4.99-5.88) cm/s. The mechanical cardiac time intervals generally remained more stable throughout the second half of pregnancy, although, with increased gestational age, there was an increase in duration of septal and RV atrial contraction, LV pre-ejection and septal and RV ventricular ejection, while there was a decrease in duration of septal postejection. Regression equations used for the construction of gestational age-specific reference ranges for peak myocardial velocities, Em/Am ratios, mechanical cardiac time intervals and cMPI are presented. Conclusion Peak myocardial velocities increase with gestational age, while the mechanical time intervals remain more stable throughout the second half of pregnancy. Using an automated method to analyze cTDI-derived myocardial velocity traces, it was possible to construct reference ranges, which could be used in distinguishing between normal and abnormal fetal cardiac function.
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| 4. |
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| 5. |
- Rondelet, A., et al.
(författare)
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Clathrin's adaptor interaction sites are repurposed to stabilize microtubules during mitosis
- 2020
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Ingår i: Journal of Cell Biology. - : Rockefeller University Press. - 0021-9525 .- 1540-8140. ; 219:2
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Tidskriftsartikel (refereegranskat)abstract
- Clathrin ensures mitotic spindle stability and efficient chromosome alignment, independently of its vesicle trafficking function. Although clathrin localizes to the mitotic spindle and kinetochore fiber microtubule bundles, the mechanisms by which clathrin stabilizes microtubules are unclear. We show that clathrin adaptor interaction sites on clathrin heavy chain (CHC) are repurposed during mitosis to directly recruit the microtubule-stabilizing protein GTSE1 to the spindle. Structural analyses reveal that these sites interact directly with clathrin-box motifs on GTSE1. Disruption of this interaction releases GTSE1 from spindles, causing defects in chromosome alignment. Surprisingly, this disruption destabilizes astral microtubules, but not kinetochore-microtubule attachments, and chromosome alignment defects are due to a failure of chromosome congression independent of kinetochore-microtubule attachment stability. GTSE1 recruited to the spindle by clathrin stabilizes microtubules by inhibiting the microtubule depolymerase MCAK. This work uncovers a novel role of clathrin adaptor-type interactions to stabilize nonkinetochore fiber microtubules to support chromosome congression, defining for the first time a repurposing of this endocytic interaction mechanism during mitosis.
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| 6. |
- Ryden, Mikael, et al.
(författare)
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Transplanted Bone Marrow-Derived Cells Contribute to Human Adipogenesis
- 2015
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Ingår i: Cell Metabolism. - : Elsevier BV. - 1550-4131 .- 1932-7420. ; 22:3, s. 408-417
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Tidskriftsartikel (refereegranskat)abstract
- Because human white adipocytes display a high turnover throughout adulthood, a continuous supply of precursor cells is required to maintain adipogenesis. Bone marrow (BM)-derived progenitor cells may contribute to mammalian adipogenesis; however, results in animal models are conflicting. Here we demonstrate in 65 subjects who underwent allogeneic BM or peripheral blood stem cell (PBSC) transplantation that, over the entire lifespan, BM/PBSC-derived progenitor cells contribute similar to 10% to the subcutaneous adipocyte population. While this is independent of gender, age, and different transplantation-related parameters, body fat mass exerts a strong influence, with up to 2.5-fold increased donor cell contribution in obese individuals. Exome and whole-genome sequencing of single adipocytes suggests that BM/PBSC-derived progenitors contribute to adipose tissue via both differentiation and cell fusion. Thus, at least in the setting of transplantation, BM serves as a reservoir for adipocyte progenitors, particularly in obese subjects.
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| 7. |
- Schneider, Kara, et al.
(författare)
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Elimination of virus-like particles reduces protein aggregation and extends replicative lifespan in Saccharomyces cerevisiae
- 2024
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Ingår i: Proceedings of the National Academy of Science of the United States of America. - 0027-8424 .- 1091-6490. ; 121:14
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Tidskriftsartikel (refereegranskat)abstract
- A major consequence of aging and stress, in yeast to humans, is an increased accumulation of protein aggregates at distinct sites within the cells. Using genetic screens, immunoelectron microscopy, and three-dimensional modeling in our efforts to elucidate the importance of aggregate annexation, we found that most aggregates in yeast accumulate near the surface of mitochondria. Further, we show that virus-like particles (VLPs), which are part of the retrotransposition cycle of Ty elements, are markedly enriched in these sites of protein aggregation. RNA interference-mediated silencing of Ty expression perturbed aggregate sequestration to mitochondria, reduced overall protein aggregation, mitigated toxicity of a Huntington's disease model, and expanded the replicative lifespan of yeast in a partially Hsp104-dependent manner. The results are in line with recent data demonstrating that VLPs might act as aging factors in mammals, including humans, and extend these findings by linking VLPs to a toxic accumulation of protein aggregates and raising the possibility that they might negatively influence neurological disease progression.
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