| 1. |
- Anderzen, J., et al.
(författare)
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International benchmarking in type 1 diabetes: Large difference in childhood HbA1c between eight high-income countries but similar rise during adolescence-A quality registry study
- 2020
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Ingår i: Pediatric Diabetes. - : Hindawi Limited. - 1399-543X .- 1399-5448. ; 21:4, s. 621-627
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To identify differences and similarities in HbA1c levels and patterns regarding age and gender in eight high-income countries. Subjects 66 071 children and adolescents below18 years of age with type 1 diabetes for at least 3 months and at least one HbA1c measurement during the study period. Methods Pediatric Diabetes Quality Registry data from Austria, Denmark, England, Germany, Norway, Sweden, the United States, and Wales were collected between 2013 and 2014. HbA1c, gender, age, and duration were used in the analysis. Results Distribution of gender and age groups was similar in the eight participating countries. The mean HbA1c varied from 60 to 73 mmol/mol (7.6%-8.8%) between the countries. The increase in HbA1c between the youngest (0-9 years) to the oldest (15-17 years) age group was close to 8 mmol/mol (0.7%) in all countries (P < .001). Females had a 1 mmol/mol (0.1%) higher mean HbA1c than boys (P < .001) in seven out of eight countries. Conclusions In spite of large differences in the mean HbA1c between countries, a remarkable similarity in the increase of HbA1c from childhood to adolescence was found.
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| 2. |
- Fitzka, M., et al.
(författare)
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High Speed In Situ Synchrotron Observation of Cyclic Deformation and Phase Transformation of Superelastic Nitinol at Ultrasonic Frequency
- 2020
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Ingår i: Experimental Mechanics. - : Springer Science and Business Media LLC. - 0014-4851 .- 1741-2765. ; 60:3, s. 317-328
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Tidskriftsartikel (refereegranskat)abstract
- The near equi-atomic intermetallic Ni Ti alloy Nitinol is used for medical implants, notably in self-expanding stent grafts and heart valve frames, which are subjected to several hundred million load cycles in service. Increasing the testing frequency to the ultrasonic range would drastically shorten the testing times and make the very-high cycle regime experimentally accessible. Such tests are, however, only meaningful if the material response at ultrasonic frequency is identical to that observed in conventional fatigue tests. A novel fatigue testing setup where superelastic Nitinol dog bone specimens are loaded at ultrasonic cycling frequency is presented. Loading conditions resemble in vivo loading (i.e., repeated cyclic loading with relatively small strain amplitudes, specimens in a pre-strained multi-phase state). Strains and phase transformations during ultrasonic frequency cycling are quantitatively measured in an X-ray diffraction (XRD) synchrotron experiment and compared to the material response at low frequency. The XRD experiment confirms that forward and reverse stress-induced phase transformation from austenite to martensite via the intermediate R-phase occurs during low frequency (0.1 Hz, strain rate ε˙ ≈ 10−3 s−1) and ultrasonic frequency (20 kHz, ε˙ ≈ 102 s−1) cycling. Since the same deformation mechanisms are active at low and ultrasonic frequency, these findings imply a general applicability of the ultrasonic fatigue testing technique to Nitinol.
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| 3. |
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| 4. |
- Phuyal, S., et al.
(författare)
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Mechanical strain stimulates COPII-dependent secretory trafficking via Rac1
- 2022
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Ingår i: Embo Journal. - : EMBO. - 0261-4189 .- 1460-2075. ; 41:18
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Tidskriftsartikel (refereegranskat)abstract
- Cells are constantly exposed to various chemical and physical stimuli. While much has been learned about the biochemical factors that regulate secretory trafficking from the endoplasmic reticulum (ER), much less is known about whether and how this trafficking is subject to regulation by mechanical signals. Here, we show that subjecting cells to mechanical strain both induces the formation of ER exit sites (ERES) and accelerates ER-to-Golgi trafficking. We found that cells with impaired ERES function were less capable of expanding their surface area when placed under mechanical stress and were more prone to develop plasma membrane defects when subjected to stretching. Thus, coupling of ERES function to mechanotransduction appears to confer resistance of cells to mechanical stress. Furthermore, we show that the coupling of mechanotransduction to ERES formation was mediated via a previously unappreciated ER-localized pool of the small GTPase Rac1. Mechanistically, we show that Rac1 interacts with the small GTPase Sar1 to drive budding of COPII carriers and stimulates ER-to-Golgi transport. This interaction therefore represents an unprecedented link between mechanical strain and export from the ER.
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| 5. |
- Reiterer, M, et al.
(författare)
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Acute and chronic hypoxia differentially predispose lungs for metastases
- 2019
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 10246-
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Tidskriftsartikel (refereegranskat)abstract
- Oscillations in oxygen levels affect malignant cell growth, survival, and metastasis, but also somatic cell behaviour. In this work, we studied the effect of the differential expression of the two primary hypoxia inducible transcription factor isoforms, HIF-1α and HIF-2α, and pulmonary hypoxia to investigate how the hypoxia response of the vascular endothelium remodels the lung pre-metastatic niche. Molecular responses to acute versus chronic tissue hypoxia have been proposed to involve dynamic HIF stabilization, but the downstream consequences and the extent to which differential lengths of exposure to hypoxia can affect HIF-isoform activation and secondary organ pre-disposition for metastasis is unknown. We used primary pulmonary endothelial cells and mouse models with pulmonary endothelium-specific deletion of HIF-1α or HIF-2α, to characterise their roles in vascular integrity, inflammation and metastatic take after acute and chronic hypoxia. We found that acute hypoxic response results in increased lung metastatic tumours, caused by HIF-1α-dependent endothelial cell death and increased microvascular permeability, in turn facilitating extravasation. This is potentiated by the recruitment and retention of specific myeloid cells that further support a pro-metastatic environment. We also found that chronic hypoxia delays tumour growth to levels similar to those seen in normoxia, and in a HIF-2α-specific fashion, correlating with increased endothelial cell viability and vascular integrity. Deletion of endothelial HIF-2α rendered the lung environment more vulnerable to tumour cell seeding and growth. These results demonstrate that the nature of the hypoxic challenge strongly influences the nature of the endothelial cell response, and affects critical parameters of the pulmonary microenvironment, significantly impacting metastatic burden. Additionally, this work establishes endothelial cells as important players in lung remodelling and metastatic progression.
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| 6. |
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| 7. |
- Reiterer, M, et al.
(författare)
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Hyperoxia Reprogrammes Microvascular Endothelial Cell Response to Hypoxia in an Organ-Specific Manner
- 2022
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Ingår i: Cells. - : MDPI AG. - 2073-4409. ; 11:16
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Tidskriftsartikel (refereegranskat)abstract
- Organ function relies on microvascular networks to maintain homeostatic equilibrium, which varies widely in different organs and during different physiological challenges. The endothelium role in this critical process can only be evaluated in physiologically relevant contexts. Comparing the responses to oxygen flux in primary murine microvascular EC (MVEC) obtained from brain and lung tissue reveals that supra-physiological oxygen tensions can compromise MVEC viability. Brain MVEC lose mitochondrial activity and undergo significant alterations in electron transport chain (ETC) composition when cultured under standard, non-physiological atmospheric oxygen levels. While glycolytic capacity of both lung and brain MVEC are unchanged by environmental oxygen, the ability to trigger a metabolic shift when oxygen levels drop is greatly compromised following exposure to hyperoxia. This is particularly striking in MVEC from the brain. This work demonstrates that the unique metabolism and function of organ-specific MVEC (1) can be reprogrammed by external oxygen, (2) that this reprogramming can compromise MVEC survival and, importantly, (3) that ex vivo modelling of endothelial function is significantly affected by culture conditions. It further demonstrates that physiological, metabolic and functional studies performed in non-physiological environments do not represent cell function in situ, and this has serious implications in the interpretation of cell-based pre-clinical models.
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