| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
- Nilsson, Hans, et al.
(författare)
-
Evolution of the ion environment of comet 67P/Churyumov-Gerasimenko
- 2015
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 583
-
Tidskriftsartikel (refereegranskat)abstract
- Context. The Rosetta spacecraft is escorting comet 67P/Churyumov-Gerasimenko from a heliocentric distance of >3.6 AU, where the comet activity was low, until perihelion at 1.24 AU. Initially, the solar wind permeates the thin comet atmosphere formed from sublimation. Aims. Using the Rosetta Plasma Consortium Ion Composition Analyzer (RPC-ICA), we study the gradual evolution of the comet ion environment, from the first detectable traces of water ions to the stage where cometary water ions accelerated to about 1 keV energy are abundant. We compare ion fluxes of solar wind and cometary origin. Methods. RPC-ICA is an ion mass spectrometer measuring ions of solar wind and cometary origins in the 10 eV-40 keV energy range. Results. We show how the flux of accelerated water ions with energies above 120 eV increases between 3.6 and 2.0 AU. The 24 h average increases by 4 orders of magnitude, mainly because high-flux periods become more common. The water ion energy spectra also become broader with time. This may indicate a larger and more uniform source region. At 2.0 AU the accelerated water ion flux is frequently of the same order as the solar wind proton flux. Water ions of 120 eV-few keV energy may thus constitute a significant part of the ions sputtering the nucleus surface. The ion density and mass in the comet vicinity is dominated by ions of cometary origin. The solar wind is deflected and the energy spectra broadened compared to an undisturbed solar wind. Conclusions. The flux of accelerated water ions moving from the upstream direction back toward the nucleus is a strongly nonlinear function of the heliocentric distance.
|
|
| 5. |
|
|
| 6. |
- Edberg, Niklas J. T., et al.
(författare)
-
Spatial distribution of low-energy plasma around comet 67P/CG from Rosetta measurements
- 2015
-
Ingår i: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 42:11, s. 4263-4269
-
Tidskriftsartikel (refereegranskat)abstract
- We use measurements from the Rosetta plasma consortium Langmuir probe and mutual impedance probe to study the spatial distribution of low-energy plasma in the near-nucleus coma of comet 67P/Churyumov-Gerasimenko. The spatial distribution is highly structured with the highest density in the summer hemisphere and above the region connecting the two main lobes of the comet, i.e., the neck region. There is a clear correlation with the neutral density and the plasma to neutral density ratio is found to be approximate to 1-210(-6), at a cometocentric distance of 10km and at 3.1AU from the Sun. A clear 6.2h modulation of the plasma is seen as the neck is exposed twice per rotation. The electron density of the collisionless plasma within 260km from the nucleus falls off with radial distance as approximate to 1/r. The spatial structure indicates that local ionization of neutral gas is the dominant source of low-energy plasma around the comet.
|
|
| 7. |
- Mandt, K. E., et al.
(författare)
-
RPC observation of the development and evolution of plasma interaction boundaries at 67P/Churyumov-Gerasimenko
- 2016
-
Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 462, s. S9-S22
-
Tidskriftsartikel (refereegranskat)abstract
- One of the primary objectives of the Rosetta Plasma Consortium, a suite of five plasma instruments on-board the Rosetta spacecraft, is to observe the formation and evolution of plasma interaction regions at the comet 67P/Churyumov-Gerasimenko (67P/CG). Observations made between 2015 April and 2016 February show that solar wind-cometary plasma interaction boundaries and regions formed around 2015 mid-April and lasted through early 2016 January. At least two regions were observed, separated by an ion-neutral collisionopause boundary. The inner region was located on the nucleus side of the boundary and was characterized by low-energy water-group ions, reduced magnetic field pileup and enhanced electron densities. The outer region was located outside of the boundary and was characterized by reduced electron densities, water-group ions that are accelerated to energies above 100 eV and enhanced magnetic field pileup compared to the inner region. The boundary discussed here is outside of the diamagnetic cavity and shows characteristics similar to observations made on-board the Giotto spacecraft in the ion pileup region at 1P/Halley. We find that the boundary is likely to be related to ion-neutral collisions and that its location is influenced by variability in the neutral density and the solar wind dynamic pressure.
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
- Edberg, Niklas J. T., et al.
(författare)
-
Solar wind interaction with comet 67P : Impacts of corotating interaction regions
- 2016
-
Ingår i: Journal of Geophysical Research - Space Physics. - 2169-9380 .- 2169-9402. ; 121:2, s. 949-965
-
Tidskriftsartikel (refereegranskat)abstract
- We present observations from the Rosetta Plasma Consortium of the effects of stormy solar wind on comet 67P/Churyumov-Gerasimenko. Four corotating interaction regions (CIRs), where the first event has possibly merged with a coronal mass ejection, are traced from Earth via Mars (using Mars Express and Mars Atmosphere and Volatile EvolutioN mission) to comet 67P from October to December 2014. When the comet is 3.1-2.7AU from the Sun and the neutral outgassing rate approximate to 10(25)-10(26)s(-1), the CIRs significantly influence the cometary plasma environment at altitudes down to 10-30km. The ionospheric low-energy (approximate to 5eV) plasma density increases significantly in all events, by a factor of >2 in events 1 and 2 but less in events 3 and 4. The spacecraft potential drops below -20V upon impact when the flux of electrons increases. The increased density is likely caused by compression of the plasma environment, increased particle impact ionization, and possibly charge exchange processes and acceleration of mass-loaded plasma back to the comet ionosphere. During all events, the fluxes of suprathermal (approximate to 10-100eV) electrons increase significantly, suggesting that the heating mechanism of these electrons is coupled to the solar wind energy input. At impact the magnetic field strength in the coma increases by a factor of 2-5 as more interplanetary magnetic field piles up around the comet. During two CIR impact events, we observe possible plasma boundaries forming, or moving past Rosetta, as the strong solar wind compresses the cometary plasma environment. We also discuss the possibility of seeing some signatures of the ionospheric response to tail disconnection events.
|
|
| 11. |
- Harvey, B. P., et al.
(författare)
-
Evolution of marine organisms under climate change at different levels of biological organisation
- 2014
-
Ingår i: Water. - : MDPI AG. - 2073-4441. ; 6:11, s. 3545-3574
-
Tidskriftsartikel (refereegranskat)abstract
- Research to date has suggested that both individual marine species and ecologicalprocesses are expected to exhibit diverse responses to the environmental effects of climatechange. Evolutionary responses can occur on rapid (ecological) timescales, and yet studiestypically do not consider the role that adaptive evolution will play in modulating biologicalresponses to climate change. Investigations into such responses have typically been focusedat particular biological levels (e.g., cellular, population, community), often lackinginteractions among levels. Since all levels of biological organisation are sensitive to globalclimate change, there is a need to elucidate how different processes and hierarchicalinteractions will influence species fitness. Therefore, predicting the responses ofcommunities and populations to global change will require multidisciplinary efforts acrossmultiple levels of hierarchy, from the genetic and cellular to communities and ecosystems.Eventually, this may allow us to establish the role that acclimatisation and adaptation willplay in determining marine community structures in future scenarios.
|
|
| 12. |
- Hollman, P, et al.
(författare)
-
Tribological evaluation of thermally activated CVD diamond-like carbon (DLC) coatings
- 1997
-
Ingår i: SURFACE & COATINGS TECHNOLOGY. - 0257-8972. ; 96:2-3, s. 230-235
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Diamond-lie carbon coatings have been the subject of expanding technological interest for wear resistance and low friction applications during recent years. In this study diamond-like carbon coatings were deposited by thermally activated chemical vapour
|
|
| 13. |
|
|
| 14. |
|
|
| 15. |
|
|
| 16. |
|
|
| 17. |
- Lundqvist, Björn, et al.
(författare)
-
Thermal conductivity of isotopically enriched silicon carbide
- 2013
-
Ingår i: THERMINIC 2013 - 19th International Workshop on Thermal Investigations of ICs and Systems, Proceedings. - : IEEE. ; , s. 58-61, s. 58-61
-
Konferensbidrag (refereegranskat)abstract
- Since the semiconductor silicon carbide presents attractive opportunities for the fabrication of novel electronic devices, there is significant interest in improving its material quality. Shrinking component sizes and high demands for efficiency and reliability make the capability to release excess heat an important factor for further development. Experience from Si and Diamond tells us that isotopic enrichment is a possible way to increase the thermal conductivity. We have produced samples of 4H-SiC that contain 28Si and 12C to a purity of 99.5%. The thermal conductivity in the c-direction of these samples has been measured by a transient thermoreflectance method. An improvement due to enrichment of at least 18% was found. The result is valid for a temperature of 45K above room temperature. A preliminary study of the temperature dependence of the thermal conductivity demonstrates a strong temperature dependence in agreement with earlier reports for 4H. © 2013 IEEE.
|
|
| 18. |
|
|
| 19. |
|
|
| 20. |
|
|
| 21. |
- Sjöberg, Klas, et al.
(författare)
-
Autoimmune markers in lymphoid malignancies.
- 2008
-
Ingår i: Scandinavian Journal of Immunology. - : Wiley. - 1365-3083 .- 0300-9475. ; 67:5, s. 509-515
-
Tidskriftsartikel (refereegranskat)abstract
- Chronic immune stimulation such as Helicobacter pylori (hp) infection, Sjögren's syndrome or coeliac disease may initiate non-Hodgkin lymphoma (NHL). The opposite (appearance of autoimmunity) has also been reported. The aim of this study was to describe the pattern of these immune markers in patients with lymphoid malignancies. Sera from 96 patients with NHL (median age 72, range 38-88, F/M 41/55) were analysed with ELISA to determine the frequency of antibodies against guinea pig (gp) and human recombinant (hr) transglutaminase type 2 (Tg2), and hr factor XIII subunit a* (part of the Tg-family), extractable nuclear antigen (ENA), and hp. As hp antibodies decrease in younger age cohorts a sex- and age-matched control group of 768 persons was used. The control population for transglutaminase antibodies consisted of 59 blood donors, (median 42 years, range 19-65) was analysed with a commercial kit. Gp-Tg2-IgG positivity was documented in 72% and hr-Tg2-IgG positivity in 15% (5% positive controls for both; P < 0.001 and ns, respectively). For IgA 3% had gp-Tg2 and 4% hr-Tg2 (5% in controls: ns for both). Anti-FXIII-IgA positivity was found in 22% (5% in controls; P = 0.03). Unspecific anti-ENA-IgG positivity was found in 24% (P < 0.001), while only 2% had specific ENA autoantibodies. Moreover, 36% were positive for anti-hp-IgG, while controls were positive in 54% (P < 0.001). The frequency of unspecific autoantibodies was increased. No differences could be noted in specific autoantibodies (hr-Tg2-IgA). In contrast, fewer than expected were anti-hp-positive. A defective immune response, similar to that in autoimmune diseases, could contribute to the pathogenesis of lymphoid malignancies.
|
|
| 22. |
|
|
| 23. |
|
|
| 24. |
|
|
| 25. |
|
|
| 26. |
|
|
| 27. |
- Volwerk, M., et al.
(författare)
-
Mass-loading, pile-up, and mirror-mode waves at comet 67P/Churyumov-Gerasimenko
- 2016
-
Ingår i: Annales Geophysicae. - : Copernicus GmbH. - 0992-7689 .- 1432-0576. ; 34:1, s. 1-15
-
Tidskriftsartikel (refereegranskat)abstract
- The data from all Rosetta plasma consortium instruments and from the ROSINA COPS instrument are used to study the interaction of the solar wind with the outgassing cometary nucleus of 67P/Churyumov-Gerasimenko. During 6 and 7 June 2015, the interaction was first dominated by an increase in the solar wind dynamic pressure, caused by a higher solar wind ion density. This pressure compressed the draped magnetic field around the comet, and the increase in solar wind electrons enhanced the ionization of the outflow gas through collisional ionization. The new ions are picked up by the solar wind magnetic field, and create a ring/ring-beam distribution, which, in a high-beta plasma, is unstable for mirror mode wave generation. Two different kinds of mirror modes are observed: one of small size generated by locally ionized water and one of large size generated by ionization and pick-up farther away from the comet.
|
|
| 28. |
|
|
| 29. |
- André, Mats, et al.
(författare)
-
Lower hybrid waves at comet 67P/Churyumov-Gerasimenko
- 2017
-
Ingår i: Monthly notices of the Royal Astronomical Society. - : OXFORD UNIV PRESS. - 0035-8711 .- 1365-2966. ; 469, s. S29-S38
-
Tidskriftsartikel (refereegranskat)abstract
- We investigate the generation of waves in the lower hybrid frequency range by density gradients in the near plasma environment of comet 67P/Churyumov-Gerasimenko. When the plasma is dominated by water ions from the comet, a situation with magnetized electrons and unmagnetized ions is favourable for the generation of lower hybrid waves. These waves can transfer energy between ions and electrons and reshape the plasma environment of the comet. We consider cometocentric distances out to a few hundred km. We find that when the electron motion is not significantly interrupted by collisions with neutrals, large average gradients within tens of km of the comet, as well as often observed local large density gradients at larger distances, are often likely to be favourable for the generation of lower hybrid waves. Overall, we find that waves in the lower hybrid frequency range are likely to be common in the near plasma environment.
|
|
| 30. |
- Assaf, Sara, et al.
(författare)
-
Asthma in the era of COVID-19
- 2023
-
Ingår i: Respiratory Medicine. - 0954-6111. ; 218
-
Tidskriftsartikel (refereegranskat)abstract
- Since its global invasion in 2019, COVID-19 has affected several aspects of patients’ lives and posed a significant impact on the health care system. Several patient populations were identified to be at high risk of contracting SARS-CoV-2 infection and/or developing severe COVID-19-related sequelae. Conversely, anyone who has contracted SARS-CoV-2 is at risk to experience symptoms and signs consistent with post-COVID manifestations. Patients with asthma were initially thought to be at increased risk and severity for SARS-CoV-2 infection. However, accumulating evidence demonstrates that asthma endotypes/phenotypes and comorbidities influence the risk stratification in this population. Furthermore, initial concerns about the potentially increased risk of poor outcomes with asthma treatments such as inhaled corticosteroids and biologics have not been substantiated. In this review, we provide an update on COVID-19 and asthma, including risk of susceptibility, clinical manifestations and course in this population as well as discuss recommendations for management.
|
|
| 31. |
|
|
| 32. |
- Behar, Etienne, et al.
(författare)
-
The root of a comet tail : Rosetta ion observations at comet 67P/Churyumov–Gerasimenko
- 2018
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 616
-
Tidskriftsartikel (refereegranskat)abstract
- Context.The first 1000 km of the ion tail of comet 67P/Churyumov–Gerasimenko were explored by the EuropeanRosettaspacecraft,2.7 au away from the Sun.Aims.We characterised the dynamics of both the solar wind and the cometary ions on the night-side of the comet’s atmosphere.Methods.We analysed in situ ion and magnetic field measurements and compared the data to a semi-analytical model.Results.The cometary ions are observed flowing close to radially away from the nucleus during the entire excursion. The solar windis deflected by its interaction with the new-born cometary ions. Two concentric regions appear, an inner region dominated by theexpanding cometary ions and an outer region dominated by the solar wind particles.Conclusions.The single night-side excursion operated byRosettarevealed that the near radial flow of the cometary ions can beexplained by the combined action of three different electric field components, resulting from the ion motion, the electron pressuregradients, and the magnetic field draping. The observed solar wind deflection is governed mostly by the motional electric field−uion×B.
|
|
| 33. |
|
|
| 34. |
- Brindefalk, B., et al.
(författare)
-
Bacterial composition in Swedish raw drinking water reveals three major interacting ubiquitous metacommunities
- 2022
-
Ingår i: Microbiologyopen. - : Wiley. - 2045-8827. ; 11:5
-
Tidskriftsartikel (refereegranskat)abstract
- Background Surface raw water used as a source for drinking water production is a critical resource, sensitive to contamination. We conducted a study on Swedish raw water sources, aiming to identify mutually co-occurring metacommunities of bacteria, and environmental factors driving such patterns. Methods The water sources were different regarding nutrient composition, water quality, and climate characteristics, and displayed various degrees of anthropogenic impact. Water inlet samples were collected at six drinking water treatment plants over 3 years, totaling 230 samples. The bacterial communities of DNA sequenced samples (n = 175), obtained by 16S metabarcoding, were analyzed using a joint model for taxa abundance. Results Two major groups of well-defined metacommunities of microorganisms were identified, in addition to a third, less distinct, and taxonomically more diverse group. These three metacommunities showed various associations to the measured environmental data. Predictions for the well-defined metacommunities revealed differing sets of favored metabolic pathways and life strategies. In one community, taxa with methanogenic metabolism were common, while a second community was dominated by taxa with carbohydrate and lipid-focused metabolism. Conclusion The identification of ubiquitous persistent co-occurring bacterial metacommunities in freshwater habitats could potentially facilitate microbial source tracking analysis of contamination issues in freshwater sources.
|
|
| 35. |
- Cedervall, T, et al.
(författare)
-
Allosteric and temperature effects on the plasma protein binding by streptococcal M protein family members
- 1995
-
Ingår i: Scandinavian Journal of Immunology. - : Wiley. - 0300-9475 .- 1365-3083. ; 42:4, s. 41-433
-
Tidskriftsartikel (refereegranskat)abstract
- Most group A streptococcal strains bind immunoglobulins (Ig) and fibrinogen to their cell walls. It is shown in this paper that the Ig-binding of three different strains was much weaker at 37 degrees C than at room temperature (20 degrees C), whereas the fibrinogen binding was unaffected by temperature. The binding properties and molecular sizes of two purified group A streptococcal cell surface proteins from the M protein family were studied at various temperatures, M1 protein with affinity for IgG, fibrinogen and albumin, and protein Sir22 with affinity for IgA and IgG. Both proteins appeared as monomers which bound all their ligands, including fibrinogen, very weakly at 37 degrees C, and as strongly binding dimers at 10 and 20 degrees C. Furthermore, the results demonstrated that the plasma protein binding of the bacterial proteins was allosterically regulated, i.e. the binding of a ligand to one site modulated the binding of a ligand to a second site. For example, the binding of albumin or IgG to purified M1 protein at 10 and 20 degrees C strongly enhanced the binding of fibrinogen at 37 degrees C. This indicates that the high affinity dimer form of the bacterial proteins can be stabilized at 37 degrees C, a possible explanation for the strong fibrinogen binding of whole bacteria. Finally, the sizes and binding properties of three M1 protein fragments were studied and the results indicated that the centrally located C-repeats, which are conserved among the members of the M protein family, are important for the formation of the high-affinity dimers of the bacterial proteins.
|
|
| 36. |
|
|
| 37. |
- De Chiara, Matteo, et al.
(författare)
-
Domestication reprogrammed the budding yeast life cycle
- 2022
-
Ingår i: Nature Ecology & Evolution. - : Springer Science and Business Media LLC. - 2397-334X .- 2397-334X. ; 6
-
Tidskriftsartikel (refereegranskat)abstract
- Domestication of plants and animals is the foundation for feeding the world human population but can profoundly alter the biology of the domesticated species. Here we investigated the effect of domestication on one of our prime model organisms, the yeast Saccharomyces cerevisiae, at a species-wide level. We tracked the capacity for sexual and asexual reproduction and the chronological life span across a global collection of 1,011 genome-sequenced yeast isolates and found a remarkable dichotomy between domesticated and wild strains. Domestication had systematically enhanced fermentative and reduced respiratory asexual growth, altered the tolerance to many stresses and abolished or impaired the sexual life cycle. The chronological life span remained largely unaffected by domestication and was instead dictated by clade-specific evolution. We traced the genetic origins of the yeast domestication syndrome using genome-wide association analysis and genetic engineering and disclosed causative effects of aneuploidy, gene presence/absence variations, copy number variations and single-nucleotide polymorphisms. Overall, we propose domestication to be the most dramatic event in budding yeast evolution, raising questions about how much domestication has distorted our understanding of the natural biology of this key model species.
|
|
| 38. |
- de Peppo, G.M., et al.
(författare)
-
Human Embryonic Mesodermal Progenitors Highly Resemble Human Mesenchymal Stem Cells and Display High Potential for Tissue Engineering Applications
- 2010
-
Ingår i: Tissue Engineering. Part A. - : Mary Ann Liebert. - 1937-3341 .- 1937-335X. ; 16:7, s. 2161-2182
-
Tidskriftsartikel (refereegranskat)abstract
- Adult stem cells, such as human mesenchymal stem cells (hMSCs), show limited proliferative capacity and, after long-term culture, lose their differentiation capacity and are therefore not an optimal cell source for tissue engineering. Human embryonic stem cells (hESCs) constitute an important new resource in this field, but one major drawback is the risk of tumor formation in the recipients. One alternative is to use progenitor cells derived from hESCs which are more lineage restricted but do not form teratomas. We have recently derived a cell line from hESCs denoted human embryonic stem cell-derived mesodermal progenitors (hESMPs) and here, using genome wide microarray analysis, report that the process of hES-MPs derivation results in a significantly altered expression of hESCs characteristic genes to an expression level highly similar to that of hMSCs. However, hES-MPs displayed a significantly higher proliferative capacity and longer telomeres. Interestingly, the hES-MPs also demonstrated a lower expression of HLA class II proteins before and after interferon-γ treatment, indicating that these cells may somewhat be immunoprivileged and potentially used for HLA-incompatible transplantation. The hES-MPs are thus an appealing alternative to hMSCs in tissue engineering applications and stem cell-based therapies for mesodermal tissues.
|
|
| 39. |
- Edberg, Niklas J. T., et al.
(författare)
-
CME impact on comet 67P/Churyumov-Gerasimenko
- 2016
-
Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 462, s. S45-S56
-
Tidskriftsartikel (refereegranskat)abstract
- We present Rosetta observations from comet 67P/Churyumov-Gerasimenko during the impact of a coronal mass ejection (CME). The CME impacted on 2015 Oct 5-6, when Rosetta was about 800 km from the comet nucleus, and 1.4 au from the Sun. Upon impact, the plasma environment is compressed to the level that solar wind ions, not seen a few days earlier when at 1500 km, now reach Rosetta. In response to the compression, the flux of suprathermal electrons increases by a factor of 5-10 and the background magnetic field strength increases by a factor of similar to 2.5. The plasma density increases by a factor of 10 and reaches 600 cm(-3), due to increased particle impact ionization, charge exchange and the adiabatic compression of the plasma environment. We also observe unprecedentedly large magnetic field spikes at 800 km, reaching above 200 nT, which are interpreted as magnetic flux ropes. We suggest that these could possibly be formed by magnetic reconnection processes in the coma as the magnetic field across the CME changes polarity, or as a consequence of strong shears causing Kelvin-Helmholtz instabilities in the plasma flow. Due to the limited orbit of Rosetta, we are not able to observe if a tail disconnection occurs during the CME impact, which could be expected based on previous remote observations of other CME-comet interactions.
|
|
| 40. |
- Edenius, C, et al.
(författare)
-
INHIBITION OF MICROSOMAL PROSTAGLANDIN E SYNTHASE-1 (MPGES-1) BY GS-248 REDUCES PROSTAGLANDIN E2 BIOSYNTHESIS WHILE INCREASING PROSTACYCLIN IN HUMAN SUBJECTS
- 2020
-
Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 79, s. 1099-1099
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Microsomal prostaglandin E synthase-1 (mPGES-1) catalyzes the formation prostaglandin (PG) E2from cyclooxygenase derived PGH2(1, 2). Inhibition of mPGES-1 leads to reduction of pro-inflammatory PGE2, while in vessels there is a concomitant increase of vasoprotective prostacyclin (PGI2) via shunting of PGH2(3,4). Apart from relieving symptoms in experimental animal models of inflammation, inhibitors of mPGES-1 cause relaxation of human medium sized arteries(4)and resistance arteries(5). The prostaglandin profile following mPGES-1 inhibition, explains the anti-inflammatory effects and also opens for the possibility of treating inflammatory diseases with concomitant vasculopathies. GS-248 is a potent and selective inhibitor of mPGES-1 exhibiting sub-nanomolar IC50in human whole bloodex vivo.Objectives:To evaluate safety, tolerability, pharmacokinetics and pharmacodynamics of GS-248.Methods:Healthy males and females (age 18–73 years) were included in the study. Six cohorts were administrated single oral doses of 1-300mg GS-248 (n=36) or placebo (n=12), three cohorts were administered once daily doses of 20-180mg GS-248 (n=18) or placebo (n=12) over ten days. In addition, 8 subjects were treated in a separate cohort with 200mg celecoxib bid for ten days. Blood samples were drawn for measurement of GS-248 exposure and production of PGE2after LPS incubationex vivo. The content of PGE2and PGI2metabolites was measured in urine. All analyses were performed by LC-MS/MS.Results:GS-248 was safe and well tolerated at all tested dose levels. Maximum plasma concentration was achieved 1 - 2.5 hours after dosing, and half-life was about 10 hours. Induced PGE2formationex vivo,catalyzed by mPGES-1, was completely inhibited for 24 hours after a single low dose (40mg) of GS-248. In urine, GS-248 dose-dependently reduced the excretion of PGE2metabolite by more than 50% whereas the excretion of PGI2metabolite increased more than twice the baseline levels. In the celecoxib cohort urinary metabolites of both PGE2and PGI2were reduced with approx 50%.Conclusion:GS-248 at investigated oral doses was safe and well tolerated. There was a sustained inhibition of LPS induced PGE2formation in whole blood. In urine, there was a metabolite shift showing reduced PGE2and increased PGI2, while celecoxib reduced both PGE2and PGI2metabolites. This suggests that selective inhibition of mPGES-1 results in systemic shunting of PGH2to PGI2formation, leading to anti-inflammatory and vasodilatory effects, while preventing platelet activation. The results warrant further evaluation of GS-248 in inflammatory conditions with vasculopathies such as Digital Ulcers and Raynaud’s Phenomenon in Systemic Sclerosis.References:[1]Korotkova M, Jakobsson PJ. Persisting eicosanoid pathways in rheumatic diseases. Nat Rev Rheumatol. 2014;10:229-41[2]Bergqvist F, Morgenstern R, Jakobsson PJ. A review on mPGES-1 inhibitors: From preclinical studies to clinical applications. Prostaglandins Other Lipid Mediat. 2019;147:106383[3]Kirkby NS, et al. Mechanistic definition of the cardiovascular mPGES-1/COX-2/ADMA axis. Cardiovasc Res. 2020[4]Ozen G, et al. Inhibition of microsomal PGE synthase-1 reduces human vascular tone by increasing PGI2: a safer alternative to COX-2 inhibition. Br J Pharmacol. 2017;174:4087-98[5]Larsson K, et al. Biological characterization of new inhibitors of microsomal PGE synthase-1 in preclinical models of inflammation and vascular tone. Br J Pharmacol. 2019;176:4625-38Disclosure of Interests:Charlotte Edenius Shareholder of: Gesynta Pharma, Consultant of: Gesynta Pharma,, Gunilla Ekström Shareholder of: Gesynta Pharma, Consultant of: Gesynta Pharma,, Johan Kolmert Consultant of: Gesynta Pharma,, Ralf Morgenstern Shareholder of: Gesynta Pharma, Employee of: Gesynta Pharma, Patric Stenberg Shareholder of: Gesynta Pharma, Employee of: Gesynta Pharma, Per-Johan Jakobsson Shareholder of: Gesynta Pharma, Grant/research support from: Gesynta Pharma, AstraZeneca,, Göran Tornling Shareholder of: Gesynta Pharma, Vicore Pharma,, Consultant of: Gesynta Pharma, Vicore Pharma, AnaMar
|
|
| 41. |
- Engelhardt, Ilka. A. D., et al.
(författare)
-
Plasma Density Structures at Comet 67P/Churyumov-Gerasimenko
- 2018
-
Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 477:1, s. 1296-1307
-
Tidskriftsartikel (refereegranskat)abstract
- We present Rosetta RPC case study from four events at various radial distance, phase angle and local time from autumn 2015, just after perihelion of comet 67P/Churyumov-Gerasimenko. Pulse like (high amplitude, up to minutes in time) signatures are seen with several RPC instruments in the plasma density (LAP, MIP), ion energy and flux (ICA) as well as magnetic field intensity (MAG). Furthermore the cometocentric distance relative to the electron exobase is seen to be a good organizing parameter for the measured plasma variations. The closer Rosetta is to this boundary, the more pulses are measured. This is consistent with the pulses being filaments of plasma originating from the diamagnetic cavity boundary as predicted by simulations.
|
|
| 42. |
- Ermilova, Inna, et al.
(författare)
-
Quantum chemical and molecular dynamics modelling of hydroxylated polybrominated diphenyl ethers
- 2017
-
Ingår i: Physical Chemistry, Chemical Physics - PCCP. - : Royal Society of Chemistry (RSC). - 1463-9076 .- 1463-9084. ; 19:41, s. 28263-28274
-
Tidskriftsartikel (refereegranskat)abstract
- A series of 19 hydroxylated polybrominated diphenyl ethers (OH-PBDEs) have been studied using density functional theory (DFT) and molecular dynamics simulations with the purpose of investigating eventual correlations between their physicochemical properties and toxic action. Dissociation constants (pK(a)), solvation free energies and octanol-water partition coefficients (logP) have been computed. Additionally, metadynamics simulations of OH-PBDEs passing through a lipid bilayer have been carried out for four OH-PBDE species. No correlations between computed pKa values and toxicity data have been found. Medium correlations were found between partition coefficients and the ability of OH-PBDEs to alter membrane potential in cell cultures, which is attributed to higher uptake of molecules with larger log P parameters. It was also demonstrated that in lipid bilayers, OH-PBDE molecules differ in their orientational distributions and can adopt different conformations which can affect the uptake of these molecules and influence the pathways of their toxic action.
|
|
| 43. |
- Gunell, H., et al.
(författare)
-
Ion acoustic waves at comet 67P/Churyumov-Gerasimenko : Observations and computations
- 2017
-
Ingår i: Astronomy and Astrophysics. - : EDP SCIENCES S A. - 0004-6361 .- 1432-0746. ; 600
-
Tidskriftsartikel (refereegranskat)abstract
- Context. On 20 January 2015 the Rosetta spacecraft was at a heliocentric distance of 2.5 AU, accompanying comet 67P/Churyumov-Gerasimenko on its journey toward the Sun. The Ion Composition Analyser (RPC-ICA), other instruments of the Rosetta Plasma Consortium, and the ROSINA instrument made observations relevant to the generation of plasma waves in the cometary environment.Aims. Observations of plasma waves by the Rosetta Plasma Consortium Langmuir probe (RPC-LAP) can be explained by dispersion relations calculated based on measurements of ions by the Rosetta Plasma Consortium Ion Composition Analyser (RPC-ICA), and this gives insight into the relationship between plasma phenomena and the neutral coma, which is observed by the Comet Pressure Sensor of the Rosetta Orbiter Spectrometer for Ion and Neutral Analysis instrument (ROSINA-COPS).Methods. We use the simple pole expansion technique to compute dispersion relations for waves on ion timescales based on the observed ion distribution functions. These dispersion relations are then compared to the waves that are observed. Data from the instruments RPC-LAP, RPC-ICA and the mutual impedance probe (RPC-MIP) are compared to find the best estimate of the plasma density.Results. We find that ion acoustic waves are present in the plasma at comet 67P/Churyumov-Gerasimenko, where the major ion species is H2O+. The bulk of the ion distribution is cold, k(B)T(i) = 0.01 eV when the ion acoustic waves are observed. At times when the neutral density is high, ions are heated through acceleration by the solar wind electric field and scattered in collisions with the neutrals. This process heats the ions to about 1 eV, which leads to significant damping of the ion acoustic waves.Conclusions. In conclusion, we show that ion acoustic waves appear in the H2O+ plasmas at comet 67P/Churyumov-Gerasimenko and how the interaction between the neutral and ion populations affects the wave properties.
|
|
| 44. |
- Gunell, Herbert, et al.
(författare)
-
Plasma waves confined to the diamagnetic cavity of comet 67P/Churyumov-Gerasimenko
- 2017
-
Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press. - 0035-8711 .- 1365-2966. ; 469, s. S84-S92
-
Tidskriftsartikel (refereegranskat)abstract
- Ion acoustic waves were observed in the diamagnetic cavity of comet 67P/Churyumov-Gerasimenko by the Rosetta spacecraft on 2015 August 3, when the comet was 1.25 au from the Sun. Wave spectra recorded by the Langmuir probe (RPC-LAP), peak near 200 Hz, decrease for higher frequencies and reach the noise floor at approximately 1.5 kHz. These waves were observed only when the spacecraft was in the diamagnetic cavity or at its boundary, which is identified as a sharp drop in magnetic field magnitude, measured by RPC-MAG. The plasma, on both sides of the boundary, is dominated by a cold (a few hundred K) water group ion population, one cold (k(B)T(e) similar to 0.1 eV) and one warm (k(B)T(e) similar to 10 eV) electron population. The observations are interpreted in terms of current-driven ion acoustic waves, generated by currents that flow through bulges on the boundary of the diamagnetic cavity.
|
|
| 45. |
- Hallberg, D, et al.
(författare)
-
Donor-derived myofibroblasts in the ocular surface after allogeneic haematopoetic stem cell transplantation
- 2006
-
Ingår i: Acta Ophthalmologica Scandinavica. - 1395-3907. ; 84, s. 774-780
-
Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT. Purpose: To identify and characterize cells of donor origin in the ocular surface of female recipients who have undergone allogeneic haematopoietic stem cell transplantation (allo-SCT) from a male donor. Methods: Cytological impressions from the eyes of nine allografted patients (17 eyes) were analysed. Donor cells were identified using sex-chromosomespecific fluorescence in situ hybridization (FISH). Cells were characterized by immunohistochemistry (IHC) using the CK3 and CK19 epithelial markers, the panleucocytic marker CD45 and the myofibroblast marker a-SMA. Results: No epithelial cells of donor origin were observed in the corneal or conjunctival samples. Cells of donor origin were found in the corneal samples, although these were often too degraded to allow characterization by IHC. In the conjunctiva, a median of 86% of the total number of cells were of recipient origin, including a subgroup (2%) of giant cells exhibiting polyploidy (range 4–18 n), found in the limbal region. Donor cells were detected in the conjunctiva of all nine patients at a median ratio of 9%, of which two-thirds were CD45+⁄ a-SMA+. Conclusions: We observed superficially located myofibroblasts of donor origin in all allografted patients, but not in samples from healthy controls. Whether myofibroblasts are implicated in ocular graft-versus-host disease requires further studies.
|
|
| 46. |
- Holmdahl, Idun, et al.
(författare)
-
Early Life Wheeze and Risk Factors for Asthma-A Revisit at Age 7 in the GEWAC-Cohort
- 2021
-
Ingår i: Children. - : MDPI. - 2227-9067. ; 8:6
-
Tidskriftsartikel (refereegranskat)abstract
- One third of all toddlers are in need of medical care because of acute wheeze and many of these children have persistent asthma at school age. Our aims were to assess risk factors for and the prevalence of asthma at age 7 in a cohort of children suffering from an acute wheezing episode as toddlers. A total of 113 children, included during an acute wheezing episode (cases), and 54 healthy controls were followed prospectively from early pre-school age to 7 years. The protocol included questionnaires, ACT, FeNO, nasopharyngeal virus samples, blood sampling for cell count, vitamin D levels, and IgE to food and airborne allergens. The prevalence of asthma at age 7 was 70.8% among cases and 1.9% among controls (p < 0.001). Acute wheeze caused by rhinovirus (RV) infection at inclusion was more common among cases with asthma at age 7 compared to cases without asthma (p = 0.011) and this association remained significant following adjustment for infection with other viruses (OR 3.8, 95% CI 1.4-10.5). Cases with asthma at age 7 had been admitted to hospital more often (p = 0.024) and spent more days admitted (p = 0.01) during the year following inclusion compared to cases without asthma. RV infection stands out as the main associated factor for wheeze evolving to persistent asthma. Cases who developed asthma also had an increased need of hospital time and care for wheeze during the year after inclusion.
|
|
| 47. |
- Imhagen, Annika, 1972-, et al.
(författare)
-
Levels of Physical Activity, Enjoyment, Self-Efficacy for Exercise, and Social Support Before and After Metabolic and Bariatric Surgery : a Longitudinal Prospective Observational Study
- 2023
-
Ingår i: Obesity Surgery. - : Springer. - 0960-8923 .- 1708-0428. ; 33:12, s. 3899-3906
-
Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Physical activity (PA) after metabolic and bariatric surgery (MBS) can influence weight loss, health status, and quality of life. Known mediators to participate in PA are enjoyment, self-efficacy, and social support. Little is known about PA behavior in MBS individuals. The aim of this study was to explore levels of PA and the PA mediators enjoyment, self-efficacy, and social support before and after MBS and to investigate changes over time.METHODS: Adults scheduled to undergo MBS were recruited from a Swedish university hospital. Accelerometer-measured and self-reported PA, body weight, and PA mediators were collected at baseline and at 12 to 18 months post-surgery.RESULTS: Among 90 individuals included, 50 completed the follow-up assessment and had valid accelerometer data. Sedentary time (minutes/day) was unchanged, but sedentary time as percentage of wear time decreased significantly from 67.2% to 64.5% (p<0.05). Time spent in light PA and total PA increased significantly from 259.3 to 288.7 min/day (p < 0.05) and from 270.5 to 303.5 min/day (p < 0.01), respectively. Step counts increased significantly from 6013 to 7460 steps/day (p < 0.01). There was a significant increase in self-reported PA, enjoyment, self-efficacy for exercise, and positive social support from family. The increase in PA mediators did not lead to a significant change in time spent in moderate to vigorous PA.CONCLUSION: The increase in PA-mediators was not associated with an increase in moderate to vigorous PA, but the strengthened PA mediators suggest potential for an increase in moderate to vigorous PA in patients undergoing MBS.
|
|
| 48. |
|
|
| 49. |
- Jivegård, Lennart, 1950, et al.
(författare)
-
Effects of three months of low molecular weight heparin (dalteparin) treatment after bypass surgery for lower limb ischemia--a randomised placebo-controlled double blind multicentre trial.
- 2005
-
Ingår i: European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery. - : Elsevier BV. - 1078-5884. ; 29:2, s. 190-8
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To test the hypothesis that long-term postoperative dalteparin (Fragmin), Pharmacia Corp) treatment improves primary patency of peripheral arterial bypass grafts (PABG) in lower limb ischemia patients on acetylsalicylic acid (ASA) treatment. DESIGN: Prospective randomised double blind multicenter study. MATERIALS AND METHODS: Using a computer algorithm 284 patients with lower limb ischemia, most with pre-operative ischemic ulceration or partial gangrene, from 12 hospitals were randomised, after PABG, to 5000 IU dalteparin or placebo injections once daily for 3 months. All patients received 75 mg of ASA daily for 12 months. Graft patency was assessed at 1, 3 and 12 months. RESULTS: At 1 year, 42 patients had died or were lost to follow-up. Compliance with the injection schedule was 80%. Primary patency rate, in the dalteparin versus the control group, respectively, was 83 versus 80% (n.s.) at 3 months and 59% for both groups at 12 months. Major complication rates and cardiovascular morbidity were not different between the two groups. CONCLUSIONS: In patients on ASA treatment, long-term postoperative dalteparin treatment did not improve patency after peripheral artery bypass grafting. Therefore, low molecular weight heparin treatment cannot be recommended for routine use after bypass surgery for critical lower limb ischemia.
|
|
| 50. |
- Johansson, Fredrik, et al.
(författare)
-
Plasma densities, flow, and solar EUV flux at comet 67P : A cross-calibration approach
- 2021
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 653
-
Tidskriftsartikel (refereegranskat)abstract
- Context. During its two-year mission at comet 67P, Rosetta nearly continuously monitored the inner coma plasma environment for gas production rates varying over three orders of magnitude, at distances to the nucleus ranging from a few to a few hundred kilometres. To achieve the best possible measurements, cross-calibration of the plasma instruments is needed. Aims. Our goal is to provide a consistent plasma density dataset for the full mission, while in the process providing a statistical characterisation of the plasma in the inner coma and its evolution.Methods. We constructed physical models for two different methods to cross-calibrate the spacecraft potential and the ion current as measured by the Rosetta Langmuir probes (LAP) to the electron density as measured by the Mutual Impedance Probe (MIP). We also described the methods used to estimate spacecraft potential, and validated the results with the Ion Composition Analyser (ICA).Results. We retrieve a continuous plasma density dataset for the entire cometary mission with a much improved dynamical range compared to any plasma instrument alone and, at times, improve the temporal resolution from 0.24-0.74 Hz to 57.8 Hz. The physical model also yields, at a three-hour time resolution, ion flow speeds and a proxy for the solar EUV flux from the photoemission from the Langmuir probes.Conclusions. We report on two independent mission-wide estimates of the ion flow speed that are consistent with the bulk H2O+ ion velocities as measured by the ICA. We find the ion flow to consistently be much faster than the neutral gas over the entire mission, lending further evidence that the ions are collisionally decoupled from the neutrals in the coma. Measurements of ion speeds from Rosetta are therefore not consistent with the assumptions made in previously published plasma density models of the comet 67P's ionosphere at the start and end of the mission. Also, the measured EUV flux is perfectly consistent with independently derived values previously published from LAP and lends support for the conclusions drawn regarding an attenuation of solar EUV from a distant nanograin dust population, when the comet activity was high. The new density dataset is consistent with the existing MIP density dataset, but it facilitates plasma analysis on much shorter timescales, and it also covers long time periods where densities were too low to be measured by MIP.
|
|
