| 1. |
- Meech, K. J., et al.
(författare)
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EPOXI: Comet 103P/Hartley 2 Observations from a Worldwide Campaign
- 2011
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Ingår i: Astrophysical Journal Letters. - London : IOP. - 2041-8213 .- 2041-8205. ; 734:L1, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- Earth- and space-based observations provide synergistic information for space mission encounters by providing data over longer timescales, at different wavelengths and using techniques that are impossible with an in situ flyby. We report here such observations in support of the EPOXI spacecraft flyby of comet 103P/Hartley 2. The nucleus is small and dark, and exhibited a very rapidly changing rotation period. Prior to the onset of activity, the period was ~16.4?hr. Starting in 2010 August the period changed from 16.6?hr to near 19?hr in December. With respect to dust composition, most volatiles and carbon and nitrogen isotope ratios, the comet is similar to other Jupiter-family comets. What is unusual is the dominance of CO 2 -driven activity near perihelion, which likely persists out to aphelion. Near perihelion the comet nucleus was surrounded by a large halo of water-ice grains that contributed significantly to the total water production.
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| 2. |
- Singh, B. P., et al.
(författare)
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Experimental access to Transition Distribution Amplitudes with the PANDA experiment at FAIR
- 2015
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Ingår i: European Physical Journal A. Hadrons and Nuclei. - : Springer Science and Business Media LLC. - 1434-6001 .- 1434-601X. ; 51:8
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Tidskriftsartikel (refereegranskat)abstract
- Baryon-to-meson Transition Distribution Amplitudes (TDAs) encoding valuable new information on hadron structure appear as building blocks in the collinear factorized description for several types of hard exclusive reactions. In this paper, we address the possibility of accessing nucleon-to-pion (pi N) TDAs from (p) over barp -> e(+)e(-)pi(0) reaction with the future PANDA detector at the FAIR facility. At high center-of-mass energy and high invariant mass squared of the lepton pair q(2), the amplitude of the signal channel (p) over barp -> e(+)e(-)pi(0) admits a QCD factorized description in terms of pi N TDAs and nucleon Distribution Amplitudes (DAs) in the forward aid backward kinematic regimes. Assuming the validity of this factorized description, we perform feasibility studies for measuring (p) over barp -> e(+)e(-)pi(0) with the PANDA detector. Detailed simulations on signal reconstruction efficiency as well as on rejection of the most severe background channel, i.e. (p) over barp -> pi(+)pi(-)pi(0) were performed for the center-of-mass energy squared s = 5 GeV2 and s = 10 GeV2, in the kinematic regions 3.0 < q(2) < 4.3 GeV2 and 5 < q(2) < 9 GeV2, respectively, with a neutral pion scattered in the forward or backward cone vertical bar cos theta(pi 0)vertical bar > 0.5 in the proton-antiproton center-of-mass frame. Results of the simulation show that the particle identification capabilities of the PANDA detector will allow to achieve a background rejection factor of 5 . 10(7) (1 . 10(7)) at low (high) q(2) for s = 5 GeV2, and of 1 . 10(8) (6 . 10(6)) at low (high) q(2) for s = 10 GeV2, while keeping the signal reconstruction efficiency at around 40%. At both energies, a clean lepton signal can be reconstructed with the expected statistics corresponding to 2 of integrated luminosity. The cross sections obtained from the simulations are used to show that a test of QCD collinear factorization can be done at the lowest order by measuring scaling laws and angular distributions. The future measurement of the signal channel cross section with PANDA will provide a new test of the perturbative QCD description of a novel class of hard exclusive reactions and will open the possibility of experimentally accessing pi N TDAs.
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| 3. |
- Erni, W., et al.
(författare)
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Technical design report for the PANDA (AntiProton Annihilations at Darmstadt) Straw Tube Tracker
- 2013
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Ingår i: European Physical Journal A. Hadrons and Nuclei. - : Springer Science and Business Media LLC. - 1434-6001 .- 1434-601X. ; 49:2
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Tidskriftsartikel (refereegranskat)abstract
- This document describes the technical layout and the expected performance of the Straw Tube Tracker (STT), the main tracking detector of the PANDA target spectrometer. The STT encloses a Micro-Vertex-Detector (MVD) for the inner tracking and is followed in beam direction by a set of GEM stations. The tasks of the STT are the measurement of the particle momentum from the reconstructed trajectory and the measurement of the specific energy loss for a particle identification. Dedicated simulations with full analysis studies of certain proton-antiproton reactions, identified as being benchmark tests for the whole PANDA scientific program, have been performed to test the STT layout and performance. The results are presented, and the time lines to construct the STT are described.
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| 4. |
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| 5. |
- Carr, C., et al.
(författare)
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RPC : The rosetta plasma consortium
- 2007
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Ingår i: Space Science Reviews. - : Springer Science and Business Media LLC. - 0038-6308 .- 1572-9672. ; 128:1-4, s. 629-647
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Forskningsöversikt (refereegranskat)abstract
- The Rosetta Plasma Consortium (RPC) will make in-situ measurements of the plasma enviromnent of comet 67P/Churyumov-Gerasimenko. The consortium will provide the complementary data sets necessary for an understanding of the plasma processes in the inner coma, and the structure and evolution of the coma with the increasing cometary activity. Five sensors have been selected to achieve this: the Ion and Electron Sensor (IES), the Ion Composition Analyser (ICA), the Langmuir Probe (LAP), the Mutual Impedance Probe (MIP) and the Magnetometer (MAG). The sensors interface to the spacecraft through the Plasma Interface Unit (PIU). The consortium approach allows for scientific, technical and operational coordination, and makes Optimum use of the available mass and power resources.
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| 6. |
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| 7. |
- Li, S. Y., et al.
(författare)
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Universal toxin-based selection for precise genome engineering in human cells
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
-
Tidskriftsartikel (refereegranskat)abstract
- Prokaryotic restriction enzymes, recombinases and Cas proteins are powerful DNA engineering and genome editing tools. However, in many primary cell types, the efficiency of genome editing remains low, impeding the development of gene- and cell-based therapeutic applications. A safe strategy for robust and efficient enrichment of precisely genetically engineered cells is urgently required. Here, we screen for mutations in the receptor for Diphtheria Toxin (DT) which protect human cells from DT. Selection for cells with an edited DT receptor variant enriches for simultaneously introduced, precisely targeted gene modifications at a second independent locus, such as nucleotide substitutions and DNA insertions. Our method enables the rapid generation of a homogenous cell population with bi-allelic integration of a DNA cassette at the selection locus, without clonal isolation. Toxin-based selection works in both cancer-transformed and non-transformed cells, including human induced pluripotent stem cells and human primary T-lymphocytes, as well as it is applicable also in vivo, in mice with humanized liver. This work represents a flexible, precise, and efficient selection strategy to engineer cells using CRISPR-Cas and base editing systems. Genome engineering in cell lines or human stem cells often has poor efficiency, limiting the development of research and therapeutic applications. Here, the authors use a toxin-based selection system for precise bi-allelic engineering in cells and in vivo.
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| 8. |
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| 9. |
- Nilsson, H., et al.
(författare)
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Investigation of the influence of magnetic anomalies on ion distributions at Mars
- 2006
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Ingår i: Space Science Reviews. - : Springer Science and Business Media LLC. - 0038-6308 .- 1572-9672. ; 126:1-4, s. 355-372
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Tidskriftsartikel (refereegranskat)abstract
- Using data from the Mars Express Ion Mass Analyzer (IMA) we investigate the distribution of ion beams of planetary origin and search for an influence from Mars crustal magnetic anomalies. We have concentrated on ion beams observed inside the induced magnetosphere boundary (magnetic pile-up boundary). Some north-south asymmetry is seen in the data, but no longitudinal structure resembling that of the crustal anomalies. Comparing the occurrence rate of ion beams with magnetic field strength at 400 km altitude below the spacecraft (using statistical Mars Global Surveyor results) shows a decrease of the occurrence rate for modest (< 40 nT) magnetic fields. Higher magnetic field regions (above 40 nT at 400 km) are sampled so seldom that the statistics are poor but the data is consistent with some ion outflow events being closely associated with the stronger anomalies. This ion flow does not significantly affect the overall distribution of ion beams around Mars.
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| 10. |
- Sävblom, C, et al.
(författare)
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Association between polymorphisms in the prostate-specific antigen (PSA) promoter and release of PSA
- 2009
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Ingår i: International Journal of Andrology. - : Wiley-Blackwell. - 0105-6263 .- 1365-2605. ; 32:5, s. 479-485
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Tidskriftsartikel (refereegranskat)abstract
- Variations in serum prostate-specific antigen (PSA) have been ascribed to A/G nucleotide polymorphisms located at -158 bp (rs266882) and -4643 bp (rs925013), relative to the transcription start site within the promoter of the PSA gene. PSA is also an androgen receptor target (AR) gene and polymorphisms in AR gene are known to affect AR function. Our objective was to compare the impact of these A/G polymorphisms separately or in combination with AR CAG micro satellite on regulation of PSA secretion into seminal plasma and blood in young men. Leukocyte DNA was extracted from 291 conscripts and genotyping performed with the Sequenom Mass Array System. PSA was measured with an immunofluorometric assay. Linear regression analysis was used to test the association of polymorphism frequencies with serum and seminal plasma levels of PSA. PSA gene polymorphisms at -158 bp or -4643 bp did not alone influence total PSA (tPSA) levels in seminal plasma or in blood. Homozygotes for the A-allele at -158 bp in combination with CAG > 22 had significantly higher serum levels of tPSA than subjects carrying the G-allele (p = 0.01). In conclusion, the PSA gene polymorphisms did not importantly influence the levels of tPSA in seminal plasma or in blood. tPSA in serum was influenced by interactions between PSA promoter variants and AR CAG polymorphism.
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| 11. |
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| 12. |
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| 13. |
- Wimberger, Sandra, 1987, et al.
(författare)
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Simultaneous inhibition of DNA-PK and Pol ϴ improves integration efficiency and precision of genome editing
- 2023
-
Ingår i: Nature Communications. ; 14:1
-
Tidskriftsartikel (refereegranskat)abstract
- Genome editing, specifically CRISPR/Cas9 technology, has revolutionized biomedical research and offers potential cures for genetic diseases. Despite rapid progress, low efficiency of targeted DNA integration and generation of unintended mutations represent major limitations for genome editing applications caused by the interplay with DNA double-strand break repair pathways. To address this, we conduct a large-scale compound library screen to identify targets for enhancing targeted genome insertions. Our study reveals DNA-dependent protein kinase (DNA-PK) as the most effective target to improve CRISPR/Cas9-mediated insertions, confirming previous findings. We extensively characterize AZD7648, a selective DNA-PK inhibitor, and find it to significantly enhance precise gene editing. We further improve integration efficiency and precision by inhibiting DNA polymerase theta (Pol ϴ). The combined treatment, named 2iHDR, boosts templated insertions to 80% efficiency with minimal unintended insertions and deletions. Notably, 2iHDR also reduces off-target effects of Cas9, greatly enhancing the fidelity and performance of CRISPR/Cas9 gene editing. Low efficiency of target DNA integration remains a challenge in genome engineering. Here the authors perform large-scale compound library and genetic screens to identify targets that enhance gene editing: they see that combined DNA-PK and Pol ϴ inhibition with potent compounds increases editing efficiency and precision.
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| 14. |
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| 15. |
- Arvelius, S., et al.
(författare)
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Statistical study of relationships between dayside high-altitude and high-latitude O+ ion outflows, solar winds, and geomagnetic activity
- 2005
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Ingår i: Annales Geophysicae. - : Copernicus GmbH. - 0992-7689 .- 1432-0576. ; 23, s. 1909-1916
-
Tidskriftsartikel (refereegranskat)abstract
- The persistent outflows of O+ ions observed by the Cluster CIS/CODIF instrument were studied statistically in the high-altitude (from 3 up to 11 RE) and high-latitude (from 70 to ~90 deg invariant latitude, ILAT) polar region. The principal results are: (1) Outflowing O+ ions with more than 1keV are observed above 10 RE geocentric distance and above 85deg ILAT location; (2) at 6-8 RE geocentric distance, the latitudinal distribution of O+ ion outflow is consistent with velocity filter dispersion from a source equatorward and below the spacecraft (e.g. the cusp/cleft); (3) however, at 8-12 RE geocentric distance the distribution of O+ outflows cannot be explained by velocity filter only. The results suggest that additional energization or acceleration processes for outflowing O+ ions occur at high altitudes and high latitudes in the dayside polar region.
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| 16. |
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| 17. |
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| 18. |
- Carlsson, Ella, et al.
(författare)
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Analysis of the mass composition of the escaping plasma at Mars
- 2006
-
Ingår i: 2006 European Geosciences Union General Assembly (EGU 2006), Austria Center Vienna, Vienna (Austria), 2-7 Apr 2006. - : European Geosciences Union (EGU).
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Results from Mars Express, Mars Exploration Rovers and Mars Global Surveyor indicate that Mars harbored large amounts of liquid water on the surface in the past. In order for the water-associated geomorphologic features to form, the pressure in the atmosphere must have been at least a hundred times higher to produce the necessary greenhouse effect required to hold liquid water stable. The present atmospheric pressure is only 6-9 mbar and moreover, the spectral imaging of Mars suggests that the amount of carbonates stored in the surface is too low in order to explain the denser atmosphere in the past. This controversy led us to investigate the escaping plasma by analyzing the data from the IMA sensor (Ion Mass Analyzer) of the ASPERA-3 instrument suite onboard Mars Express. The IMA sensor measures the differential flow of ion components in the energy range of 0.01-30 keV/q.Since the instrument design was optimized for studies of plasma dynamics, the mass resolution is not adequate enough to directly resolve CO+2 from O+2 , which is the main molecular ion composing the Mars ionosphere according to theoretical models. Therefore, a special multi-species fitting technique, using calibration and in-flight data, was developed to resolve the CO+2 peak from the neighboring and much more intense O+2 peak. This technique was applied to the observations covering the period from April 4, 2004 to October 2, 2005. The events of heavy ion escape were identified inside the induced magnetosphere boundary and the Martian eclipse. We report the results of statistical studies of these ion-beam events which permitted to determine CO+2 / O+ and the O+2 / O+ ratio of the escaping plasma at Mars.
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| 19. |
- Carlsson, Ella, et al.
(författare)
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Mass composition of the escaping plasma at Mars
- 2006
-
Ingår i: Icarus. - : Elsevier BV. - 0019-1035 .- 1090-2643. ; 182:2, s. 320-328
-
Tidskriftsartikel (refereegranskat)abstract
- Data from the Ion Mass Analyzer (IMA) sensor of the ASPERA-3 instrument suite on Mars Express have been analyzed to determine the mass composition of the escaping ion species at Mars. We have examined 77 different ion-beam events and we present the results in terms of flux ratios between the following ion species: CO2+/O+ and O-2(+)/O+. The following ratios averaged over all events and energies were identified: CO2+/O+ = 0.2 and O-2(+)/O+ = 0.9. The values measured are significantly higher, by a factor of 10 for O-2(+)/O+, than a contemporary modeled ratio for the maximum fluxes which the martian ionosphere can supply. The most abundant ion species was found to be O+, followed by O-2(+) and CO2+. We estimate the loss of CO2+ to be 4.0 x 10(24) s(-1) (0.29 kg s(-1)) by using the previous measurements of Phobos-2 in our calculations. The dependence of the ion ratios in relation to their energy ranges we studied, 0.3-3.0 keV, indicated that no clear correlation was found.
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| 20. |
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| 21. |
- Fischer, R, et al.
(författare)
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Towards a transnational system of supersites for forest monitoring and research in Europe - an overview on present state and future recommendations
- 2011
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Ingår i: IForest. - : Italian Society of Sivilculture and Forest Ecology (SISEF). - 1971-7458. ; 4:1, s. 167-171
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Tidskriftsartikel (refereegranskat)abstract
- Science based approaches in addressing future risks and challenges for forests require close collaboration among the communities operating different monitoring and research networks as well as experts in process and large-scale modelling. Results of the COST FP0903 conference which took place in October 2010 in Rome, reveal valuable results from different European forest monitoring and research networks. However, the need for closer integration of these activities is obvious. In this paper, representatives from major European networks recommend a new approach for forest monitoring and research in Europe, based on a reasonable number of highly instrumented "supersites" and a larger number of intensive monitoring plots linked to these. This system needs to be built on existing infrastructures but requires increased coordination, harmonisation and a joint long term platform for data exchange and modelling.
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| 22. |
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| 23. |
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| 24. |
- Geny, Sylvain, et al.
(författare)
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Next-generation bis-locked nucleic acids with stacking linker and 2 '-glycylamino-LNA show enhanced DNA invasion into supercoiled duplexes
- 2016
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Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 44:5, s. 2007-2019
-
Tidskriftsartikel (refereegranskat)abstract
- Targeting and invading double-stranded DNA with synthetic oligonucleotides under physiological conditions remain a challenge. Bis-locked nucleic acids (bisLNAs) are clamp-forming oligonucleotides able to invade into supercoiled DNA via combined Hoogsteen and Watson-Crick binding. To improve the bisLNA design, we investigated its mechanism of binding. Our results suggest that bisLNAs bind via Hoogsteen-arm first, followed by Watson-Crick arm invasion, initiated at the tail. Based on this proposed hybridization mechanism, we designed next-generation bisLNAs with a novel linker able to stack to adjacent nucleobases, a new strategy previously not applied for any type of clamp-constructs. Although the Hoogsteen-arm limits the invasion, upon incorporation of the stacking linker, bisLNA invasion is significantly more efficient than for non-clamp, or nucleotide-linker containing LNA-constructs. Further improvements were obtained by substituting LNA with 2'-glycylamino-LNA, contributing a positive charge. For regular bisLNAs a 14-nt tail significantly enhances invasion. However, when two stacking linkers were incorporated, tail-less bisLNAs were able to efficiently invade. Finally, successful targeting of plasmids inside bacteria clearly demonstrates that strand invasion can take place in a biologically relevant context.
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| 25. |
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| 26. |
- Gummesson, Anders, 1973, et al.
(författare)
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Intestinal Permeability Is Associated With Visceral Adiposity in Healthy Women.
- 2011
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Ingår i: Obesity (Silver Spring, Md.). - : Wiley. - 1930-7381.
-
Tidskriftsartikel (refereegranskat)abstract
- Increased visceral fat, as opposed to subcutaneous/gluteal, most strongly relates to key metabolic dysfunctions including insulin resistance, hepatic steatosis, and inflammation. Mesenteric fat hypertrophy in patients with Crohn's disease and in experimental rodent models of gut inflammation suggest that impaired gut barrier function with increased leakage of gut-derived antigens may drive visceral lipid deposition. The aim of this study was to determine whether increased intestinal permeability is associated with visceral adiposity in healthy humans. Normal to overweight female subjects were recruited from a population-based cohort. Intestinal permeability was assessed using the ratio of urinary excretion of orally ingested sucralose to mannitol (S/M). In study 1 (n = 67), we found a positive correlation between waist circumference and S/M excretion within a time frame of urine collection consistent with permeability of the lower gastrointestinal tract (6-9 hours post-ingestion; P = 0.022). These results were followed up in study 2 (n = 55) in which we used computed tomography and dual energy X-ray absorptiometry to measure visceral and subcutaneous fat areas of the abdomen, liver fat content, and total body fat of the same women. The S/M ratio from the 6-12 h urine sample correlated with visceral fat area (P = 0.0003) and liver fat content (P = 0.004), but not with subcutaneous or total body fat. This novel finding of an association between intestinal permeability and visceral adiposity and liver fat content in healthy humans suggests that impaired gut barrier function should be further explored as a possible mediator of excess visceral fat accumulation and metabolic dysfunction.
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| 27. |
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| 28. |
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| 29. |
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| 30. |
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| 31. |
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| 32. |
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| 33. |
- Jungebluth, P, et al.
(författare)
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Retraction Statement
- 2023
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Ingår i: Respiration. - : S. Karger AG. - 1423-0356 .- 0025-7931. ; 102:5, s. 402-404
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 34. |
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| 35. |
- Kurth, F, et al.
(författare)
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Large-scale analysis of structural brain asymmetries during neurodevelopment : Associations with age and sex in 4265 children and adolescents.
- 2024
-
Ingår i: Human Brain Mapping. - 1065-9471 .- 1097-0193. ; 45:11, s. e26754-
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Tidskriftsartikel (refereegranskat)abstract
- Only a small number of studies have assessed structural differences between the two hemispheres during childhood and adolescence. However, the existing findings lack consistency or are restricted to a particular brain region, a specific brain feature, or a relatively narrow age range. Here, we investigated associations between brain asymmetry and age as well as sex in one of the largest pediatric samples to date (n = 4265), aged 1-18 years, scanned at 69 sites participating in the ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) consortium. Our study revealed that significant brain asymmetries already exist in childhood, but their magnitude and direction depend on the brain region examined and the morphometric measurement used (cortical volume or thickness, regional surface area, or subcortical volume). With respect to effects of age, some asymmetries became weaker over time while others became stronger; sometimes they even reversed direction. With respect to sex differences, the total number of regions exhibiting significant asymmetries was larger in females than in males, while the total number of measurements indicating significant asymmetries was larger in males (as we obtained more than one measurement per cortical region). The magnitude of the significant asymmetries was also greater in males. However, effect sizes for both age effects and sex differences were small. Taken together, these findings suggest that cerebral asymmetries are an inherent organizational pattern of the brain that manifests early in life. Overall, brain asymmetry appears to be relatively stable throughout childhood and adolescence, with some differential effects in males and females.
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| 36. |
- Lammer, H., et al.
(författare)
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Geophysical and Atmospheric Evolution of Habitable Planets
- 2010
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Ingår i: Astrobiology. - : Mary Ann Liebert Inc. - 1531-1074 .- 1557-8070. ; 10:1, s. 45-68
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Tidskriftsartikel (refereegranskat)abstract
- The evolution of Earth-like habitable planets is a complex process that depends on the geodynamical and geophysical environments. In particular, it is necessary that plate tectonics remain active over billions of years. These geophysically active environments are strongly coupled to a planet's host star parameters, such as mass, luminosity and activity, orbit location of the habitable zone, and the planet's initial water inventory. Depending on the host star's radiation and particle flux evolution, the composition in the thermosphere, and the availability of an active magnetic dynamo, the atmospheres of Earth-like planets within their habitable zones are differently affected due to thermal and nonthermal escape processes. For some planets, strong atmospheric escape could even effect the stability of the atmosphere.
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| 37. |
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| 38. |
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| 39. |
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| 40. |
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| 41. |
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| 42. |
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| 43. |
- Mzobe, P., et al.
(författare)
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Morphometric Control on Dissolved Organic Carbon in Subarctic Streams
- 2020
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Ingår i: Journal of Geophysical Research - Biogeosciences. - 2169-8953. ; 125:9
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Tidskriftsartikel (refereegranskat)abstract
- Climate change has the potential to alter hydrological regimes and to expand saturated areas in permafrost environments, which are important sources of organic carbon. The sources, transfer zones, and delivery mechanisms of carbon into the stream network are controlled by the morphometric properties of the catchment; however, the utility and limitations of these properties as predictors of dissolved organic carbon concentrations have rarely been systematically evaluated. This study tested the relationships between 18 morphometric indicators and observed dissolved organic carbon (DOC) concentrations in the Stordalen catchment, Sweden. Geospatial and explorative statistics were combined to assess the topographical, areal, and linear indicators influencing the distribution of DOC in the catchment. The results suggest that catchment morphometric indicators can be used as proxies to predict DOC concentrations along a longitudinal continuum in subarctic climate regions (R2 up to 0.52). Morphometry indicators that best served as predictors of DOC concentration in the model were as follows: relief, slope length and steepness factor (LS‐factor), sediment transport capacity, and catchment area. Due to the influence that catchment form exerts in DOC spatial patterns and processing, a morphometric approach can serve as a first approximation of DOC spatial patterns within a catchment. The initial step in identifying carbon sources based on the catchment topography has the potential to allow for quick and multilevel comparison within and between catchments.
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| 44. |
- Navin, N, et al.
(författare)
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Inferring tumor progression from genomic heterogeneity
- 2010
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Ingår i: Genome research. - : Cold Spring Harbor Laboratory. - 1549-5469 .- 1088-9051. ; 20:1, s. 68-80
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Tidskriftsartikel (refereegranskat)abstract
- Cancer progression in humans is difficult to infer because we do not routinely sample patients at multiple stages of their disease. However, heterogeneous breast tumors provide a unique opportunity to study human tumor progression because they still contain evidence of early and intermediate subpopulations in the form of the phylogenetic relationships. We have developed a method we call Sector-Ploidy-Profiling (SPP) to study the clonal composition of breast tumors. SPP involves macro-dissecting tumors, flow-sorting genomic subpopulations by DNA content, and profiling genomes using comparative genomic hybridization (CGH). Breast carcinomas display two classes of genomic structural variation: (1) monogenomic and (2) polygenomic. Monogenomic tumors appear to contain a single major clonal subpopulation with a highly stable chromosome structure. Polygenomic tumors contain multiple clonal tumor subpopulations, which may occupy the same sectors, or separate anatomic locations. In polygenomic tumors, we show that heterogeneity can be ascribed to a few clonal subpopulations, rather than a series of gradual intermediates. By comparing multiple subpopulations from different anatomic locations, we have inferred pathways of cancer progression and the organization of tumor growth.
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| 45. |
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| 46. |
- Nilsson, H., et al.
(författare)
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Ion distributions in the vicinity of Mars : Signatures of heating and acceleration processes
- 2012
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Ingår i: Earth Planets and Space. - : Springer Science and Business Media LLC. - 1343-8832 .- 1880-5981. ; 64:2, s. 135-148
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Tidskriftsartikel (refereegranskat)abstract
- More than three years of data from the ASPERA-3 instrument on-board Mars Express has been used to compile average distribution functions of ions in and around the Mars induced magnetosphere. We present samples of average distribution functions, as well as average flux patterns based on the average distribution functions, all suitable for detailed comparison with models of the near-Mars space environment. The average heavy ion distributions close to the planet form thermal populations with a temperature of 3 to 10 eV. The distribution functions in the tail consist of two populations, one cold which is an extension of the low altitude population, and one accelerated population of ionospheric origin ions. All significant fluxes of heavy ions in the tail are tailward. The heavy ions in the magnetosheath form a plume with the flow aligned with the bow shock, and a more radial flow direction than the solar wind origin flow. Summarizing the escape processes, ionospheric ions are heated close to the planet, presumably through wave-particle interaction. These heated populations are accelerated in the tailward direction in a restricted region. Another significant escape path is through the magnetosheath. A part of the ionospheric population is likely accelerated in the radial direction, out into the magnetosheath, although pick up of an oxygen exosphere may also be a viable source for this escape. Increased energy input from the solar wind during CIR events appear to mainly increase the number flux of escaping particles, the average energy of the escaping particles is not strongly affected. Heavy ions on the dayside may precipitate and cause sputtering of the atmosphere, though fluxes are likely lower than 0.4 x 10(23) s(-1).
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| 47. |
- Odenstedt Hergès, Helena, et al.
(författare)
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Descending aortic blood flow and cardiac output: a clinical and experimental study of continuous oesophageal echo-Doppler flowmetry.
- 2001
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Ingår i: Acta anaesthesiologica Scandinavica. - 0001-5172. ; 45:2, s. 180-7
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Tidskriftsartikel (refereegranskat)abstract
- Several studies have demonstrated that perioperative optimisation of oxygen delivery and haemodynamics can reduce mortality and morbidity for high-risk surgical patients. To optimise cardiac output, reliable, continuous and "less invasive" methods for measuring cardiac output are urgently needed.Eight landrace pigs were studied during experimental repeated cardiac tamponade and 14 patients during liver transplantation. Aortic blood flow was measured by using transoesophageal echo-Doppler technique. A total of 91 paired measurements of aortic blood flow and cardiac output with different techniques were performed in the pigs and 124 paired measurements in the patients.Transoesophageal echo-Doppler did provide continuous real-time monitoring of the rapid and dramatic haemodynamic changes occurring during cardiac tamponade and during liver transplantation, while only intermittent information was obtained from the bolus thermodilution technique. Changes in haemodynamics were more difficult to detect with the "continual" cardiac output thermodilution technique. Changes in aortic blood flow closely followed changes in cardiac output determined by the bolus thermodilution technique both in pigs (r= 0.89) and in patients (r=0.80). In patients, aortic blood flow constituted about 70% of cardiac output determined by the bolus thermodilution technique.A combined echo-Doppler technique can be valuable for continuous monitoring of haemodynamic changes in the perioperative setting, and changes in aortic blood flow agree well with corresponding changes in cardiac output intermittently obtained by thermodilution cardiac output measurements. With the combined echo-Doppler technique a proper position of the Doppler beam is greatly facilitated by the M-mode echo visualisation of the aortic wall and aortic cross-sectional area is continuously measured.
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| 48. |
- Pabon-Martinez, YV, et al.
(författare)
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LNA effects on DNA binding and conformation: from single strand to duplex and triplex structures
- 2017
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7:1, s. 11043-
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Tidskriftsartikel (refereegranskat)abstract
- The anti-gene strategy is based on sequence-specific recognition of double-strand DNA by triplex forming (TFOs) or DNA strand invading oligonucleotides to modulate gene expression. To be efficient, the oligonucleotides (ONs) should target DNA selectively, with high affinity. Here we combined hybridization analysis and electrophoretic mobility shift assay with molecular dynamics (MD) simulations to better understand the underlying structural features of modified ONs in stabilizing duplex- and triplex structures. Particularly, we investigated the role played by the position and number of locked nucleic acid (LNA) substitutions in the ON when targeting a c-MYC or FXN (Frataxin) sequence. We found that LNA-containing single strand TFOs are conformationally pre-organized for major groove binding. Reduced content of LNA at consecutive positions at the 3′-end of a TFO destabilizes the triplex structure, whereas the presence of Twisted Intercalating Nucleic Acid (TINA) at the 3′-end of the TFO increases the rate and extent of triplex formation. A triplex-specific intercalating benzoquinoquinoxaline (BQQ) compound highly stabilizes LNA-containing triplex structures. Moreover, LNA-substitution in the duplex pyrimidine strand alters the double helix structure, affecting x-displacement, slide and twist favoring triplex formation through enhanced TFO major groove accommodation. Collectively, these findings should facilitate the design of potent anti-gene ONs.
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| 49. |
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