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- Correa, J., et al.
(författare)
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The PERCIVAL detector : first user experiments
- 2023
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Ingår i: Journal of Synchrotron Radiation. - 0909-0495 .- 1600-5775. ; 30, s. 242-250
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Tidskriftsartikel (refereegranskat)abstract
- The PERCIVAL detector is a CMOS imager designed for the soft X-ray regime at photon sources. Although still in its final development phase, it has recently seen its first user experiments: ptychography at a free-electron laser, holographic imaging at a storage ring and preliminary tests on X-ray photon correlation spectroscopy. The detector performed remarkably well in terms of spatial resolution achievable in the sample plane, owing to its small pixel size, large active area and very large dynamic range; but also in terms of its frame rate, which is significantly faster than traditional CCDs. In particular, it is the combination of these features which makes PERCIVAL an attractive option for soft X-ray science.
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| 8. |
- Hu, X., et al.
(författare)
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Thermal modelling of water activity on comet 67P/Churyumov-Gerasimenko with global dust mantle and plural dust-to-ice ratio
- 2017
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Ingår i: Monthly notices of the Royal Astronomical Society. - : OXFORD UNIV PRESS. - 0035-8711 .- 1365-2966. ; 469, s. S295-S311
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Tidskriftsartikel (refereegranskat)abstract
- We perform a thermo-physical analysis on water activity of comet 67P/Churyumov-Gerasimenko (67P). The sublimation of water is assumed to occur from beneath a global, desiccated dust mantle over the irregular-shaped nucleus. The concept of two thermal models, the recipe of model formulation and the strategy of application to comet 67P are described. For an accurate and efficient evaluation of energy input by insolation and self-heating over the nucleus, a Landscape data base is devised based on polyhedral shape models of the nucleus. We apply the thermal models to investigate the impact of certain parameters of nucleus properties on water production. It is found that the measured water production of 67P can be overall attributed to sublimation of water ice with a mass abundance of a few to 10 per cent beneath a uniform dust mantle of several millimetres to one centimetre in thickness. Insofar as 67P is concerned, we argue against the necessity to invoke assumptions on localized water activity, or on the distinction of active/dormant surface areas.
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| 11. |
- Janciauskiene, Sabina, et al.
(författare)
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Indirect effect of alpha-1-antitrypsin on endotoxin-induced IL-1β secretion from human PBMCs
- 2022
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Ingår i: Frontiers in Pharmacology. - : Frontiers Media SA. - 1663-9812. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Human alpha-1-antitrypsin (AAT) encoded by the SERPINA1 gene, is an acute phase glycoprotein that regulates inflammatory responses via both protease inhibitory and non-inhibitory activities. We previously reported that AAT controls ATP-induced IL-1β release from human mononuclear cells by stimulating the release of small bioactive molecules. In the current study, we aimed to elucidate the identity of these putative effectors released from human PBMCs in response to AAT, which may inhibit the LPS-induced release of IL-1β. We pre-incubated human PBMCs alone or with different preparations of AAT (4 mg/ml) for 30 min at 37°C, 5% CO2, and collected cell supernatants filtered through centrifugal filters (cutoff 3 kDa) to eliminate AAT and other high molecular weight substances. Supernatants passed through the filters were used to culture PBMCs isolated from the autologous or a heterologous donors with or without adding LPS (1 μg/ml) for 6 h. Unexpectedly, supernatants from PBMCs pre-incubated with AAT (Zemaira®), but not with other AAT preparations tested or with oxidized AAT (Zemaira®), lowered the LPS-induced release of IL-1β by about 25%–60% without affecting IL1B mRNA. The reversed-phase liquid chromatography coupled with mass spectrometry did not confirm the hypothesis that small pro-resolving lipid mediators released from PBMCs after exposure to AAT (Zemaira®) are responsible for lowering the LPS-induced IL-1β release. Distinctively from other AAT preparations, AAT (Zemaira®) and supernatants from PBMCs pre-treated with this protein contained high levels of total thiols. In line, mass spectrometry analysis revealed that AAT (Zemaira®) protein contains freer Cys232 than AAT (Prolastin®). Our data show that a free Cys232 in AAT is required for controlling LPS-induced IL-1β release from human PBMCs. Further studies characterizing AAT preparations used to treat patients with inherited AAT deficiency remains of clinical importance.
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| 12. |
- Jaric, I, et al.
(författare)
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The rearing environment persistently modulates mouse phenotypes from the molecular to the behavioural level
- 2022
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Ingår i: PLoS biology. - : Public Library of Science (PLoS). - 1545-7885. ; 20:10, s. e3001837-
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Tidskriftsartikel (refereegranskat)abstract
- The phenotype of an organism results from its genotype and the influence of the environment throughout development. Even when using animals of the same genotype, independent studies may test animals of different phenotypes, resulting in poor replicability due to genotype-by-environment interactions. Thus, genetically defined strains of mice may respond differently to experimental treatments depending on their rearing environment. However, the extent of such phenotypic plasticity and its implications for the replicability of research findings have remained unknown. Here, we examined the extent to which common environmental differences between animal facilities modulate the phenotype of genetically homogeneous (inbred) mice. We conducted a comprehensive multicentre study, whereby inbred C57BL/6J mice from a single breeding cohort were allocated to and reared in 5 different animal facilities throughout early life and adolescence, before being transported to a single test laboratory. We found persistent effects of the rearing facility on the composition and heterogeneity of the gut microbial community. These effects were paralleled by persistent differences in body weight and in the behavioural phenotype of the mice. Furthermore, we show that environmental variation among animal facilities is strong enough to influence epigenetic patterns in neurons at the level of chromatin organisation. We detected changes in chromatin organisation in the regulatory regions of genes involved in nucleosome assembly, neuronal differentiation, synaptic plasticity, and regulation of behaviour. Our findings demonstrate that common environmental differences between animal facilities may produce facility-specific phenotypes, from the molecular to the behavioural level. Furthermore, they highlight an important limitation of inferences from single-laboratory studies and thus argue that study designs should take environmental background into account to increase the robustness and replicability of findings.
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- Khanin, Vasilii M., et al.
(författare)
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Influence of 3d Transition Metal Impurities on Garnet Scintillator Afterglow
- 2020
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Ingår i: Crystal Growth and Design. - : American Chemical Society (ACS). - 1528-7483 .- 1528-7505. ; 20:5, s. 3007-3017
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Tidskriftsartikel (refereegranskat)abstract
- Garnet scintillators often suffer from undesired afterglow, the origin of which is not always well-understood. A possible origin is contamination with transition metal (TM) ions. These impurities can act as traps giving rise to afterglow. Alternatively, they may show long-lived (microsecond) d-d emission. Here we present a systematic study on the role of 3d TM impurities in (Lu,Gd)3(GaAl)5O12 garnet scintillators. Scintillator disks intentionally doped with ppm levels of Ti, V, Cr, Mn, Fe, Co, Ni, Cu, or Zn were studied to identify TM-related traps in thermoluminescence (TSL) glow curves and their role in afterglow. For Ti, V, and Cr additional TSL peaks were observed that gave rise to RT afterglow in the 10-2-103 s time range, depending on garnet composition. On the millisecond time scale long-lived red/near-infrared emission was observed from Mn and Fe impurities, explained by spin-forbidden d-d emission. We show that afterglow can be reduced by the use of ultrapure raw materials. Other solutions include bandgap engineering for the garnet host to modify trap depths and applying optical filters to block the spin-forbidden d-d emission. The present study provides an insightful overview of the role of 3d TM impurities on afterglow in Ce-doped scintillators and procedures to predict and reduce afterglow. These insights will aid the development of Ce-doped garnets with superior afterglow behavior.
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- Sievers, E., et al.
(författare)
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SRC inhibition represents a potential therapeutic strategy in liposarcoma
- 2015
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136. ; 137:11, s. 2578-2588
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Tidskriftsartikel (refereegranskat)abstract
- Liposarcomas (LS) are the most common malignant mesenchymal tumors, with an overall long-term mortality rate of 60%. LS comprise three major subtypes, i.e., well-differentiated/dedifferentiated liposarcoma (WDLS/DDLS), myxoid/round cell liposarcoma (MLS) and pleomorphic liposarcoma (PLS). Aiming at the preclinical identification of novel therapeutic options, we here investigate the functional significance of SRC in primary human LS and in LS-derived cell lines. Immunohistochemical and Western blot analyses reveal relevant levels of activated p-(Tyr416)-SRC in LS of the different subtypes with particular activation in MLS and PLS. Dysregulation of the SRC modifiers CSK and PTP1B was excluded as major reason for the activation of the kinase. Consistent siRNA-mediated knockdown of SRC or inhibition by the SRC inhibitor Dasatinib led to decreased proliferation of LS cell lines of the different subtypes, with MLS cells reacting particularly sensitive in MTT assays. Flow cytometric analyses revealed that this effect was due to a significant decrease in mitotic activity and an induction of apoptosis. SRC inhibition by Dasatinib resulted in dephosphorylation of SRC itself, its interacting partners FAK and IGF-IR as well as its downstream target AKT. Consistent with a particular role of SRC in cell motility, Dasatinib reduced the migratory and invasive potential of MLS cells in Boyden chamber and Matrigel chamber assays. In summary, we provide evidence that SRC activation plays an important role in LS biology and therefore represents a potential therapeutic target, particularly in MLS and PLS.
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| 18. |
- Thunnissen, Erik, et al.
(författare)
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The Use of Immunohistochemistry Improves the Diagnosis of Small Cell Lung Cancer and Its Differential Diagnosis. An International Reproducibility Study in a Demanding Set of Cases
- 2017
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Ingår i: Journal of Thoracic Oncology. - : Elsevier BV. - 1556-0864 .- 1556-1380. ; 12:2, s. 334-346
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The current WHO classification of lung cancer states that a diagnosis of SCLC can be reliably made on routine histological and cytological grounds but immunohistochemistry (IHC) may be required, particularly (1) in cases in which histologic features are equivocal and (2) in cases in which the pathologist wants to increase confidence in diagnosis. However, reproducibility studies based on hematoxylin and eosin-stained slides alone for SCLC versus large cell neuroendocrine carcinoma (LCNEC) have shown pairwise K scores ranging from 0.35 to 0.81. This study examines whether judicious use of IHC improves diagnostic reproducibility for SCLC.Methods: Nineteen lung pathologists studied interactive digital images of 79 tumors, predominantly neuroendocrine lung tumors. Images of resection and biopsy specimens were used to make diagnoses solely on the basis of morphologic features (level 1), morphologic features along with requested IHC staining results (level 2), and all available IHC staining results (level 3).Results: For the 19 pathologists reading all 79 cases, the rate of agreement for level 1 was 64.7%, and it increased to 73.2% and 77.5% in levels 2 and 3, respectively. With IHC, K scores for four tumor categories (SCLC, LCNEC, carcinoid tumors, and other) increased in resection samples from 0.43 to 0.60 and in biopsy specimens from 0.43 to 0.64.Conclusions: Diagnosis using hematoxylin and eosin staining alone showeds moderate agreement among pathologists in tumors with neuroendocrine morphology, but agreement improved to good in most cases with the judicious use of IHC, especially in the diagnosis of SCLC. An approach for IHC in the differential diagnosis of SCLC is provided. (C) 2017 International Association for the Study of Lung Cancer.
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