1. |
- Rajewsky, N., et al.
(author)
-
LifeTime and improving European healthcare through cell-based interceptive medicine
- 2020
-
In: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 587:7834, s. 377-386
-
Journal article (peer-reviewed)abstract
- LifeTime aims to track, understand and target human cells during the onset and progression of complex diseases and their response to therapy at single-cell resolution. This mission will be implemented through the development and integration of single-cell multi-omics and imaging, artificial intelligence and patient-derived experimental disease models during progression from health to disease. Analysis of such large molecular and clinical datasets will discover molecular mechanisms, create predictive computational models of disease progression, and reveal new drug targets and therapies. Timely detection and interception of disease embedded in an ethical and patient-centered vision will be achieved through interactions across academia, hospitals, patient-associations, health data management systems and industry. Applying this strategy to key medical challenges in cancer, neurological, infectious, chronic inflammatory and cardiovascular diseases at the single-cell level will usher in cell-based interceptive medicine in Europe over the next decade.
|
|
2. |
- van Bragt, JJMH, et al.
(author)
-
Characteristics and treatment regimens across ERS SHARP severe asthma registries
- 2020
-
In: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 55:1
-
Journal article (peer-reviewed)abstract
- Little is known about the characteristics and treatments of patients with severe asthma across Europe, but both are likely to vary. This is the first study in the European Respiratory Society Severe Heterogeneous Asthma Research collaboration, Patient-centred (SHARP) Clinical Research Collaboration and it is designed to explore these variations. Therefore, we aimed to compare characteristics of patients in European severe asthma registries and treatments before starting biologicals.This was a cross-sectional retrospective analysis of aggregated data from 11 national severe asthma registries that joined SHARP with established patient databases.Analysis of data from 3236 patients showed many differences in characteristics and lifestyle factors. Current smokers ranged from 0% (Poland and Sweden) to 9.5% (Belgium), mean body mass index ranged from 26.2 (Italy) to 30.6 kg·m−2 (the UK) and the largest difference in mean pre-bronchodilator forced expiratory volume in 1 s % predicted was 20.9% (the Netherlands versus Hungary). Before starting biologicals patients were treated differently between countries: mean inhaled corticosteroid dose ranged from 700 to 1335 µg·day−1 between those from Slovenia versus Poland when starting anti-interleukin (IL)-5 antibody and from 772 to 1344 µg·day−1 in those starting anti-IgE (Slovenia versus Spain). Maintenance oral corticosteroid use ranged from 21.0% (Belgium) to 63.0% (Sweden) and from 9.1% (Denmark) to 56.1% (the UK) in patients starting anti-IL-5 and anti-IgE, respectively.The severe asthmatic population in Europe is heterogeneous and differs in both clinical characteristics and treatment, often appearing not to comply with the current European Respiratory Society/American Thoracic Society guidelines definition of severe asthma. Treatment regimens before starting biologicals were different from inclusion criteria in clinical trials and varied between countries.
|
|
3. |
- Grun, E., et al.
(author)
-
The 2016 Feb 19 outburst of comet 67P/CG : an ESA Rosetta multi-instrument study
- 2016
-
In: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 462, s. S220-S234
-
Journal article (peer-reviewed)abstract
- On 2016 Feb 19, nine Rosetta instruments serendipitously observed an outburst of gas and dust from the nucleus of comet 67P/Churyumov-Gerasimenko. Among these instruments were cameras and spectrometers ranging from UV over visible to microwave wavelengths, in situ gas, dust and plasma instruments, and one dust collector. At 09: 40 a dust cloud developed at the edge of an image in the shadowed region of the nucleus. Over the next two hours the instruments recorded a signature of the outburst that significantly exceeded the background. The enhancement ranged from 50 per cent of the neutral gas density at Rosetta to factors > 100 of the brightness of the coma near the nucleus. Dust related phenomena (dust counts or brightness due to illuminated dust) showed the strongest enhancements (factors > 10). However, even the electron density at Rosetta increased by a factor 3 and consequently the spacecraft potential changed from similar to-16 V to -20 V during the outburst. A clear sequence of events was observed at the distance of Rosetta ( 34 km from the nucleus): within 15 min the Star Tracker camera detected fast particles (similar to 25 m s(-1)) while 100 mu m radius particles were detected by the GIADA dust instrument similar to 1 h later at a speed of 6 m s(-1). The slowest were individual mm to cm sized grains observed by the OSIRIS cameras. Although the outburst originated just outside the FOV of the instruments, the source region and the magnitude of the outburst could be determined.
|
|
4. |
- Schnieders, R, et al.
(author)
-
1H, 13C and 15N chemical shift assignment of the stem-loop 5a from the 5'-UTR of SARS-CoV-2
- 2021
-
In: Biomolecular NMR assignments. - : Springer Science and Business Media LLC. - 1874-270X .- 1874-2718. ; 15:1, s. 203-211
-
Journal article (peer-reviewed)abstract
- The SARS-CoV-2 (SCoV-2) virus is the causative agent of the ongoing COVID-19 pandemic. It contains a positive sense single-stranded RNA genome and belongs to the genus of Betacoronaviruses. The 5′- and 3′-genomic ends of the 30 kb SCoV-2 genome are potential antiviral drug targets. Major parts of these sequences are highly conserved among Betacoronaviruses and contain cis-acting RNA elements that affect RNA translation and replication. The 31 nucleotide (nt) long highly conserved stem-loop 5a (SL5a) is located within the 5′-untranslated region (5′-UTR) important for viral replication. SL5a features a U-rich asymmetric bulge and is capped with a 5′-UUUCGU-3′ hexaloop, which is also found in stem-loop 5b (SL5b). We herein report the extensive 1H, 13C and 15N resonance assignment of SL5a as basis for in-depth structural studies by solution NMR spectroscopy.
|
|
5. |
|
|
6. |
- Wacker, A, et al.
(author)
-
Secondary structure determination of conserved SARS-CoV-2 RNA elements by NMR spectroscopy
- 2020
-
In: Nucleic acids research. - : Oxford University Press (OUP). - 1362-4962 .- 0305-1048. ; 48:22, s. 12415-12435
-
Journal article (peer-reviewed)abstract
- The current pandemic situation caused by the Betacoronavirus SARS-CoV-2 (SCoV2) highlights the need for coordinated research to combat COVID-19. A particularly important aspect is the development of medication. In addition to viral proteins, structured RNA elements represent a potent alternative as drug targets. The search for drugs that target RNA requires their high-resolution structural characterization. Using nuclear magnetic resonance (NMR) spectroscopy, a worldwide consortium of NMR researchers aims to characterize potential RNA drug targets of SCoV2. Here, we report the characterization of 15 conserved RNA elements located at the 5′ end, the ribosomal frameshift segment and the 3′-untranslated region (3′-UTR) of the SCoV2 genome, their large-scale production and NMR-based secondary structure determination. The NMR data are corroborated with secondary structure probing by DMS footprinting experiments. The close agreement of NMR secondary structure determination of isolated RNA elements with DMS footprinting and NMR performed on larger RNA regions shows that the secondary structure elements fold independently. The NMR data reported here provide the basis for NMR investigations of RNA function, RNA interactions with viral and host proteins and screening campaigns to identify potential RNA binders for pharmaceutical intervention.
|
|
7. |
|
|
8. |
|
|
9. |
- Grün, E., et al.
(author)
-
Dust Measurements During Galileo's Approach to Jupiter and Io Encounter
- 1996
-
In: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 274:5286, s. 399-401
-
Journal article (peer-reviewed)abstract
- About a hundred dust impacts per day were detected during the first week in December 1995 by Galileo during its approach to Jupiter. These impacts were caused by submicrometer-sized particles that were just above the detection limit. After the closest approach to Io on 7 December, impacts of these small particles ceased. This effect is expected for dust grains emitted from Io that exit the field of view of the instrument after the flyby. The impact rate of bigger micrometer-sized dust grains continued to increase toward Jupiter. These dust particles are in orbit about Jupiter or are interplanetary grains that are gravitationally concentrated near Jupiter.
|
|
10. |
- Grün, E., et al.
(author)
-
Dust measurements in the Jovian magnetosphere
- 1997
-
In: Geophysical Research Letters. - 1944-8007. ; 24:17, s. 2171-2174
-
Journal article (peer-reviewed)abstract
- Dust measurements have been obtained with the dust detector onboard the Galileo spacecraft inside a distance of about 60RJ from Jupiter (Jupiter radius, RJ = 71,492 km) during two periods of about 8 days around Galileo's closest approaches to Ganymede on 27 June and on 6 Sept 1996. The impact rate of submicrometer-sized particles fluctuated by a factor of several hundred with a period of about 10 hours, implying that their trajectories are strongly affected by the interaction with the Jovian magnetic field. Concentrations of small dust impacts were detected at the times of Ganymede closest approaches that could be secondary ejecta particles generated upon impact of other particles onto Ganymede's surface. Micrometer-sized dust particles, which could be on bound orbits about Jupiter, are concentrated in the inner Jovian system inside about 20RJ from Jupiter.
|
|
11. |
- Grün, E., et al.
(author)
-
Galileo observes electromagnetically coupled dust in the Jovian magnetosphere
- 1998
-
In: Journal of Geophysical Research. - 2156-2202. ; 103:E9, s. 20011-20022
-
Journal article (peer-reviewed)abstract
- Measurements of dust coupled to the Jovian magnetosphere have been obtained with the dust detector on board the Galileo spacecraft. We report on data obtained during the first four orbits about Jupiter that had flybys of the Galilean satellites: Ganymede (orbits 1 and 2), Callisto (orbit 3), and Europa (orbit 4). The most prominent features observed are highly time variable dust streams recorded throughout the Jovian system. The impact rate varied by up to 2 orders of magnitude with a 5 and 10 hour periodicity, which shows a correlation with Galileo's position relative to the Jovian magnetic field. Around 20 RJ (Jupiter radius, RJ=71, 492 km) in bound a dip in the impact rate has been found consistently. At the same times, reversals by 180° in impact direction occurred. This behavior can be qualitatively explained by strong coupling of nanometer-sized dust to the Jovian magnetic field. At times of satellite flybys, enhanced rates of dust impacts have been observed, which suggests that all Galilean satellites are sources of ejecta particles. Inside about 20 RJ impacts of micrometer-sized particles have been recorded that could be particles on bound orbits about Jupiter.
|
|
12. |
- Grun, E., et al.
(author)
-
South-North and Radial Traverses through the Interplanetary Dust Cloud
- 1997
-
In: Icarus. - : Elsevier BV. - 0019-1035. ; 129:2, s. 270-288
-
Journal article (peer-reviewed)abstract
- Identical in situ dust detectors are flown on board the Galileo and Ulysses spacecraft. They record impacts of micrometeoroids in the ecliptic plane at heliocentric distances from 0.7 to 5.4 AU and in a plane almost perpendicular to the ecliptic from -79 deg to +79 deg ecliptic latitude. The combination of both Ulysses and Galileo measurements yields information about the radial and latitudinal distributions of micron- and sub-micron-sized dust in the Solar System. Two types of dust particles were found to dominate the dust flux in interplanetary space. Interplanetary micrometeoroids covering a wide mass range from 10^-16 to 10^-6 g are recorded mostly inside 3 AU and at latitudes below 30 deg. Interstellar grains with masses between 10^-14 and 10^-12 g have been positively identified outside 3 AU near the ecliptic plane and outside 1.8 AU at high ecliptic latitudes (>50 deg). Interstellar grains move on hyperbolic trajectories through the planetary system and constitute the dominant dust flux (1.5 x 10^-4 m^-2 sec^-1) in the outer Solar System and at high ecliptic latitudes. To compare and analyze the Galileo and Ulysses data sets, a new model is developed based on J. Geophys. Res. 98, 17029-17048, Divine's (1993, ``five populations of interplanetary meteoroids'' model. Both models describe the interplanetary meteoroid environment in terms of dust populations on distinct orbits. Taking into account the measured velocities and the effect of radiation pressure on small particles (described by the ratio of radiation pressure force to gravity, beta), we define four populations of meteoroids on elliptical orbits and one population on hyperbolic orbit that can fit the micrometeoroid flux observed by Galileo and Ulysses. Micrometeoroids with masses greater than 10^-10 g and negligible radiation pressure (beta = 0) orbit the Sun on low to moderately eccentric orbits and with low inclinations (<=30 deg). Populations of smaller particles with mean masses of 10^-11 g (beta = 0.3), 10^-13 g (beta = 0.8), and 5 x 10^-15 g (beta = 0.3), respectively, have components with high eccentricities and have increasingly wider inclination distributions with decreasing mass. Similarities among the orbit distributions of the small particle populations on bound orbits suggest that all are genetically related and are part of an overall micrometeoroid complex that prevails in the inner Solar System. The high-eccentricity component of the small particle populations may actually be beta-meteoroids which are not well characterized by our measurements. Our modeling suggests further that the interstellar dust flux is not reduced at Ulysses' perihelion distance (1.3 AU) and that it contributes about 30% of the total dust flux observed there.
|
|
13. |
- Hilchenbach, M., et al.
(author)
-
COMET 67P/CHURYUMOV-GERASIMENKO : CLOSE-UP on DUST PARTICLE FRAGMENTS
- 2016
-
In: Astrophysical Journal Letters. - : Institute of Physics Publishing (IOPP). - 2041-8205 .- 2041-8213. ; 816:2
-
Journal article (peer-reviewed)abstract
- The COmetary Secondary Ion Mass Analyser instrument on board ESA's Rosetta mission has collected dust particles in the coma of comet 67P/Churyumov-Gerasimenko. During the early-orbit phase of the Rosetta mission, particles and particle agglomerates have been imaged and analyzed in the inner coma at distances between 100 km and 10 km off the cometary nucleus and at more than 3 AU from the Sun. We identified 585 particles of more than 14 μm in size. The particles are collected at low impact speeds and constitute a sample of the dust particles in the inner coma impacting and fragmenting on the targets. The sizes of the particles range from 14 μm up to sub-millimeter sizes and the differential dust flux size distribution is fitted with a power law exponent of -3.1. After impact, the larger particles tend to stick together, spread out or consist of single or a group of clumps, and the flocculent morphology of the fragmented particles is revealed. The elemental composition of the dust particles is heterogeneous and the particles could contain typical silicates like olivine and pyroxenes, as well as iron sulfides. The sodium to iron elemental ratio is enriched with regard to abundances in CI carbonaceous chondrites by a factor from ∼1.5 to ∼15. No clear evidence for organic matter has been identified. The composition and morphology of the collected dust particles appear to be similar to that of interplanetary dust particles.
|
|
14. |
|
|
15. |
- Krüger, H., et al.
(author)
-
Four years of Ulysses dust data: 1996-1999
- 2001
-
In: Planetary and Space Science. - 1873-5088. ; 49:13, s. 1303-1324
-
Journal article (peer-reviewed)abstract
- The Ulysses spacecraft is orbiting the Sun on a highly inclined ellipse(/i=79°, perihelion distance 1.3 AU, aphelion distance 5.4 AU).Between January /1996 and December /1999 the spacecraft was beyond 3 AUfrom the Sun and crossed the ecliptic plane at aphelion in May /1998. Inthis 4-yr period 218 dust impacts were recorded with the dust detectoron board. We publish and analyse the complete data set of both raw andreduced data for particles with masses10-16-10-8g. Together with 1477 dust impactsrecorded between launch of Ulysses and the end of /1995 publishedearlier (Grün et al., Planet. Space Sci. 43 (/1995a) 971;Krüger et al., Planet. Space Sci. 47 (/1999b) 363), a data set of1695 dust impacts detected with the Ulysses sensor between October /1990and December /1999 is now available. The impact rate measured between1996 and 1999 was relatively constant with about 0.2 impacts per day.The impact direction of the majority of the impacts is compatible withparticles of interstellar origin, the rest are most likelyinterplanetary particles. The observed impact rate is compared with amodel for the flux of interstellar dust particles. The flux of particlesseveral micrometres in size is compared with the measurements of thedust instruments on board Pioneer 10 and Pioneer 11 beyond 3 AU (Humes,J. Geophys. Res. 85 /(1980) 5841). Between 3 and 5 AU, Pioneer resultspredict that Ulysses should have seen 5 times more (~10mum sized)particles than actually detected.
|
|
16. |
- Krüger, H., et al.
(author)
-
One year of Galileo dust data from the Jovian system: 1996
- 2001
-
In: Planetary and Space Science. - 1873-5088. ; 49:13, s. 1285-1301
-
Journal article (peer-reviewed)abstract
- The dust detector system onboard Galileo has recoding dust impacts incircumjovian space since the spacecraft was injected into a bound orbitabout Jupiter in December 1995. This is the sixth in a series of papersdedicated to presenting Galileo and Ulysses dust data. We present datafrom the Galileo dust instrument for the period January to December 1996when the spacecraft completed four orbits about Jupiter (G1, G2, C3 andE4). Data were obtained as high-resolution realtime science data orrecorded data during a time period of 100 days, or via memory read-outsduring the remaining times. Because the data transmission rate of thespacecraft is very low, the complete data set (i.e. all parametersmeasured by the instrument during impact of a dust particle) for only 2%(5353) of all particles detected could be transmitted to Earth; theother particles were only counted. Together with the data for 2883particles detected during Galileo's interplanetary cruise and publishedearlier, complete data of 8236 particles detected by the Galileo dustinstrument from 1989 to 1996 are now available. The majority ofparticles detected are tiny grains (about 10nm in radius) originatingfrom Jupiter's innermost Galilean moon Io. These grains have beendetected throughout the Jovian system and the highest impact ratesexceeded 100min-1. A small number of grains has been detectedin the close vicinity of the Galilean moons Europa, Ganymede andCallisto which belong to impact-generated dust clouds formed by (mostlysubmicrometer sized) ejecta from the surfaces of the moons (Krügeret al., /1999e. Nature 399, 558). Impacts of submicrometer to micrometersized grains have been detected throughout the Jovian system andespecially in the region between the Galilean moons.
|
|
17. |
- Krüger, H., et al.
(author)
-
Three years of Galileo dust data. II. 1993-1995
- 1999
-
In: Planetary and Space Science. - 1873-5088. ; 47:1-2, s. 85-106
-
Journal article (peer-reviewed)abstract
- Between January 1993 - December 1995, the Galileo spacecraft traversed the interplanetary space between Earth and Jupiter and arrived at Jupiter on 7 December 1995. The dust instrument onboard the spacecraft was operating during most of the time and data from the instrument were obtained via memory readouts which occurred at rates between twice per day and once per week. All events were classified by an onboard program into 24 categories. Noise events were usually restricted to the lowest categories (class 0). During Galileo's passage through Jupiter's radiation belts on 7 December 1995, several of the higher categories (classes 1 and 2) also show evidence for contamination by noise. The highest categories (class 3) were noise-free all the time. A relatively constant impact rate of interplanetary and interstellar (big) particles of 0.4 impacts per day was detected over the whole three-year time span. In the outer solar system (outside about 2.6 AU) they are mostly of interstellar origin, whereas in the inner solar system they are mostly interplanetary particles. Within about 1.7 AU from Jupiter intense streams of small dust particles were detected with impact rates of up to 20,000 per day whose impact directions are compatible with a Jovian origin. Two different populations of dust particles were detected in the Jovian magnetosphere: small stream particles during Galileo's approach to the planet and big particles concentrated closer to Jupiter between the Galilean satellites. Information about 2883 particles detected by the dust instrument during Galileo's six-year journey to Jupiter is now available.
|
|
18. |
- Krüger, H., et al.
(author)
-
Three years of Ulysses dust data: 1993-1995
- 1999
-
In: Planetary and Space Science. - 1873-5088. ; 47:3-4, s. 363-383
-
Journal article (peer-reviewed)abstract
- The Ulysses spacecraft is orbiting the Sun on a highly inclined ellipse (i = 79°). After its Jupiter flyby in 1992 at a heliocentric distance of 5.4 AU, the spacecraftreapproached the inner solar system, flew over the Suns south polar region in September 1994,crossed the ecliptic plane at a distance of 1.3 AU in March 1995, and flew over the Suns northpolar region in July 1995. We report on dust impact data obtained with the dust detector onboardUlysses between January 1993 and December 1995. We publish and analyse the complete dataset of 509 recorded impacts of dust particles with masses between 10-16 g-10-7 g. Together with 968 dust impacts from launch until the end of 1992 published earlier ([Gruuml;n et al., 1995c]), information about 1477 particles detected with theUlysses sensor between October 1990 and December 1995 is now available. The impact ratemeasured between 1993 and 1995 stayed relatively constant at about 0.4 impacts per day andvaried by less than a factor of ten. Most of the impacts recorded outside about 3.5 AU arecompatible with particles of interstellar origin. Two populations of interplanetary particles havebeen recognized: big micrometer-sized particles close to the ecliptic plane and smallsub-micrometer-sized particles at high ecliptic latitudes. The observed impact rate is comparedwith a model for the flux of interstellar dust particles which gives relatively good agreement withthe observed impact rate. No change in the instruments noise characteristics or degradation of thechanneltron could be revealed during the three-year period.
|
|