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1.
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2.
  • Campbell, PJ, et al. (författare)
  • Pan-cancer analysis of whole genomes
  • 2020
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
  • Tidskriftsartikel (refereegranskat)abstract
    • Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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3.
  • Vogel, Jacob W., et al. (författare)
  • Four distinct trajectories of tau deposition identified in Alzheimer’s disease
  • 2021
  • Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 27:5, s. 871-881
  • Tidskriftsartikel (refereegranskat)abstract
    • Alzheimer’s disease (AD) is characterized by the spread of tau pathology throughout the cerebral cortex. This spreading pattern was thought to be fairly consistent across individuals, although recent work has demonstrated substantial variability in the population with AD. Using tau-positron emission tomography scans from 1,612 individuals, we identified 4 distinct spatiotemporal trajectories of tau pathology, ranging in prevalence from 18 to 33%. We replicated previously described limbic-predominant and medial temporal lobe-sparing patterns, while also discovering posterior and lateral temporal patterns resembling atypical clinical variants of AD. These ‘subtypes’ were stable during longitudinal follow-up and were replicated in a separate sample using a different radiotracer. The subtypes presented with distinct demographic and cognitive profiles and differing longitudinal outcomes. Additionally, network diffusion models implied that pathology originates and spreads through distinct corticolimbic networks in the different subtypes. Together, our results suggest that variation in tau pathology is common and systematic, perhaps warranting a re-examination of the notion of ‘typical AD’ and a revisiting of tau pathological staging. © 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.
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4.
  • Lehr, C., et al. (författare)
  • Unveiling the two-proton halo character of 17 Ne: Exclusive measurement of quasi-free proton-knockout reactions
  • 2022
  • Ingår i: Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 827
  • Tidskriftsartikel (refereegranskat)abstract
    • The proton drip-line nucleus 17Ne is investigated experimentally in order to determine its two-proton halo character. A fully exclusive measurement of the 17Ne(p,2p)16F→15⁎O+p quasi-free one-proton knockout reaction has been performed at GSI at around 500 MeV/nucleon beam energy. All particles resulting from the scattering process have been detected. The relevant reconstructed quantities are the angles of the two protons scattered in quasi-elastic kinematics, the decay of 16F into 15O (including γ decays from excited states) and a proton, as well as the 15O+p relative-energy spectrum and the 16F momentum distributions. The latter two quantities allow an independent and consistent determination of the fractions of l=0 and l=2 motion of the valence protons in 17Ne. With a resulting relatively small l=0 component of only around 35(3)%, it is concluded that 17Ne exhibits a rather modest halo character only. The quantitative agreement of the two values deduced from the energy spectrum and the momentum distributions supports the theoretical treatment of the calculation of momentum distributions after quasi-free knockout reactions at high energies by taking into account distortions based on the Glauber theory. Moreover, the experimental data allow the separation of valence-proton knockout and knockout from the 15O core. The latter process contributes with 11.8(3.1) mb around 40% to the total proton-knockout cross section of 30.3(2.3) mb, which explains previously reported contradicting conclusions derived from inclusive cross sections.
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  • Wamers, F., et al. (författare)
  • Diverse mechanisms in proton knockout reactions from the Borromean nucleus Ne-17
  • 2023
  • Ingår i: European Physical Journal A. - : Springer. - 1434-6001 .- 1434-601X. ; 59
  • Tidskriftsartikel (refereegranskat)abstract
    • Nucleon knockout experiments using beryllium or carbon targets reveal a strong dependence of the quenching factors, i.e., the ratio (Rs) of theoretical to the experimental spectroscopic factors (C2S), on the proton-neutron asymmetry in the nucleus under study. However, this dependence is greatly reduced when a hydrogen target is used. To understand this phenomenon, exclusive H-1(Ne-17, 2p F-16) and inclusive C-12(Ne-17, 2p 1(6)F)X, 1(2)C(Ne-17, F-16)X as well as 1H(Ne-17,(16) F)X(X-denotes undetected reaction products) reactions with F-16 in the ground and excited states were anal- ysed. The longitudinal momentum distribution of F-16 and the correlations between the detached protons were studied. In the case of the carbon target, there is a significant deviation from the predictions of the eikonal model. The eikonal approximation was used to extract spectroscopic factor values (CS)-S-2. The experimental (CS)-S-2 value obtained with C target is markedly lower than that for H target. This is interpreted as rescattering due to simultaneous nucleon knockout from both reaction partners, Ne-17 and C-12.
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10.
  • Hakkaart, C, et al. (författare)
  • Copy number variants as modifiers of breast cancer risk for BRCA1/BRCA2 pathogenic variant carriers
  • 2022
  • Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 5:1, s. 1061-
  • Tidskriftsartikel (refereegranskat)abstract
    • The contribution of germline copy number variants (CNVs) to risk of developing cancer in individuals with pathogenic BRCA1 or BRCA2 variants remains relatively unknown. We conducted the largest genome-wide analysis of CNVs in 15,342 BRCA1 and 10,740 BRCA2 pathogenic variant carriers. We used these results to prioritise a candidate breast cancer risk-modifier gene for laboratory analysis and biological validation. Notably, the HR for deletions in BRCA1 suggested an elevated breast cancer risk estimate (hazard ratio (HR) = 1.21), 95% confidence interval (95% CI = 1.09–1.35) compared with non-CNV pathogenic variants. In contrast, deletions overlapping SULT1A1 suggested a decreased breast cancer risk (HR = 0.73, 95% CI 0.59-0.91) in BRCA1 pathogenic variant carriers. Functional analyses of SULT1A1 showed that reduced mRNA expression in pathogenic BRCA1 variant cells was associated with reduced cellular proliferation and reduced DNA damage after treatment with DNA damaging agents. These data provide evidence that deleterious variants in BRCA1 plus SULT1A1 deletions contribute to variable breast cancer risk in BRCA1 carriers.
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11.
  • Lacour, S., et al. (författare)
  • The mass of β Pictoris c from β Pictoris b orbital motion
  • 2021
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 654
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims. We aim to demonstrate that the presence and mass of an exoplanet can now be effectively derived from the astrometry of another exoplanet.Methods. We combined previous astrometry of β Pictoris b with a new set of observations from the GRAVITY interferometer. The orbital motion of β Pictoris b is fit using Markov chain Monte Carlo simulations in Jacobi coordinates. The inner planet, β Pictoris c, was also reobserved at a separation of 96 mas, confirming the previous orbital estimations.Results. From the astrometry of planet b only, we can (i) detect the presence of β Pictoris c and (ii) constrain its mass to 10.04(-3.10)(+4.53) M-Jup. If one adds the astrometry of β Pictoris c, the mass is narrowed down to 9.15(-1.06)(+1.08) M-Jup. The inclusion of radial velocity measurements does not affect the orbital parameters significantly, but it does slightly decrease the mass estimate to 8.89(-0.75)(+0.75) M-Jup. With a semimajor axis of 2.68 +/- 0.02 au, a period of 1221 +/- 15 days, and an eccentricity of 0.32 +/- 0.02, the orbital parameters of β Pictoris c are now constrained as precisely as those of β Pictoris b. The orbital configuration is compatible with a high-order mean-motion resonance (7:1). The impact of the resonance on the planets' dynamics would then be negligible with respect to the secular perturbations, which might have played an important role in the eccentricity excitation of the outer planet.
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12.
  • Garatti, A. Caratti o., et al. (författare)
  • The GRAVITY young stellar object survey: II. First spatially resolved observations of the CO bandhead emission in a high-mass YSO
  • 2020
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 635
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. The inner regions of the discs of high-mass young stellar objects (HMYSOs) are still poorly known due to the small angular scales and the high visual extinction involved. Aims. We deploy near-infrared spectro-interferometry to probe the inner gaseous disc in HMYSOs and investigate the origin and physical characteristics of the CO bandhead emission (2.3-2.4 m). Methods. We present the first GRAVITY/VLTI observations at high spectral (R = 4000) and spatial (mas) resolution of the CO overtone transitions in NGC2024 IRS 2. Results. The continuum emission is resolved in all baselines and is slightly asymmetric, displaying small closure phases (8). Our best ellipsoid model provides a disc inclination of 34 1, a disc major axis position angle (PA) of 166 1, and a disc diameter of 3:99 0:09 mas (or 1.69 0.04 au, at a distance of 423 pc). The small closure phase signals in the continuum are modelled with a skewed rim, originating from a pure inclination effect. For the first time, our observations spatially and spectrally resolve the first four CO bandheads. Changes in visibility, as well as differential and closure phases across the bandheads are detected. Both the size and geometry of the CO-emitting region are determined by fitting a bidimensional Gaussian to the continuum-compensated CO bandhead visibilities. The CO-emitting region has a diameter of 2.740:08 0:07 mas (1.16 0.03 au), and is located in the inner gaseous disc, well within the dusty rim, with inclination and PA matching the dusty disc geometry, which indicates that both dusty and gaseous discs are coplanar. Physical and dynamical gas conditions are inferred by modelling the CO spectrum. Finally, we derive a direct measurement of the stellar mass of M 14:7 M by combining our interferometric and spectral modelling results.
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13.
  • Garcia-Lopez, R., et al. (författare)
  • A measure of the size of the magnetospheric accretion region in TW Hydrae
  • 2020
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 584:7822, s. 547-550
  • Tidskriftsartikel (refereegranskat)abstract
    • Stars form by accreting material from their surrounding disks. There is a consensus that matter flowing through the disk is channelled onto the stellar surface by the stellar magnetic field. This is thought to be strong enough to truncate the disk close to the corotation radius, at which the disk rotates at the same rate as the star. Spectro-interferometric studies in young stellar objects show that hydrogen emission (a well known tracer of accretion activity) mostly comes from a region a few milliarcseconds across, usually located within the dust sublimation radius1–3. The origin of the hydrogen emission could be the stellar magnetosphere, a rotating wind or a disk. In the case of intermediate-mass Herbig AeBe stars, the fact that Brackett γ (Brγ) emission is spatially resolved rules out the possibility that most of the emission comes from the magnetosphere4–6 because the weak magnetic fields (some tenths of a gauss) detected in these sources7,8 result in very compact magnetospheres. In the case of T Tauri sources, their larger magnetospheres should make them easier to resolve. The small angular size of the magnetosphere (a few tenths of a milliarcsecond), however, along with the presence of winds9,10 make the interpretation of the observations challenging. Here we report optical long-baseline interferometric observations that spatially resolve the inner disk of the T Tauri star TW Hydrae. We find that the near-infrared hydrogen emission comes from a region approximately 3.5 stellar radii across. This region is within the continuum dusty disk emitting region (7 stellar radii across) and also within the corotation radius, which is twice as big. This indicates that the hydrogen emission originates in the accretion columns (funnel flows of matter accreting onto the star), as expected in magnetospheric accretion models, rather than in a wind emitted at much larger distance (more than one astronomical unit).
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14.
  • Garcia-Lopez, R., et al. (författare)
  • The GRAVITY young stellar object survey XII. The hot gas disk component in Herbig Ae/Be stars
  • 2024
  • Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 684
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. The region of protoplanetary disks closest to a star (within 1–2 au) is shaped by a number of different processes, from accretion of the disk material onto the central star to ejection in the form of winds and jets. Optical and near-IR emission lines are potentially good tracers of inner disk processes if very high spatial and/or spectral resolution are achieved. Aims. In this paper, we exploit the capabilities of the VLTI-GRAVITY near-IR interferometer to determine the location and kinematics of the hydrogen emission line Brγ. Methods. We present VLTI-GRAVITY observations of the Brγ line for a sample of 26 stars of intermediate mass (HAEBE), the largest sample so far analysed with near-IR interferometry. Results. The Brγ line was detected in 17 objects. The emission is very compact (in most cases only marginally resolved), with a size of 10–30 R∗(1–5 mas). About half of the total flux comes from even smaller regions, which are unresolved in our data. For eight objects, it was possible to determine the position angle (PA) of the line-emitting region, which is generally in agreement with that of the inner-dusty disk emitting the K-band continuum. The position-velocity pattern of the Brγ line-emitting region of the sampled objects is roughly consistent with Keplerian rotation. The exception is HD 45677, which shows more extended emission and more complex kinematics. The most likely scenario for the Brγ origin is that the emission comes from an MHD wind launched very close to the central star, in a region well within the dust sublimation radius. An origin in the bound gas layer at the disk surface cannot be ruled out, while accreting matter provides only a minor fraction of the total flux. Conclusions. These results show the potential of near-IR spectro-interferometry to study line emission in young stellar objects.
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15.
  • Khoury, J. D., et al. (författare)
  • The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms
  • 2022
  • Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 36, s. 1703-1719
  • Tidskriftsartikel (refereegranskat)abstract
    • The upcoming 5th edition of the World Health Organization (WHO) Classification of Haematolymphoid Tumours is part of an effort to hierarchically catalogue human cancers arising in various organ systems within a single relational database. This paper summarizes the new WHO classification scheme for myeloid and histiocytic/dendritic neoplasms and provides an overview of the principles and rationale underpinning changes from the prior edition. The definition and diagnosis of disease types continues to be based on multiple clinicopathologic parameters, but with refinement of diagnostic criteria and emphasis on therapeutically and/or prognostically actionable biomarkers. While a genetic basis for defining diseases is sought where possible, the classification strives to keep practical worldwide applicability in perspective. The result is an enhanced, contemporary, evidence-based classification of myeloid and histiocytic/dendritic neoplasms, rooted in molecular biology and an organizational structure that permits future scalability as new discoveries continue to inexorably inform future editions.
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16.
  • Lagrange, A. M., et al. (författare)
  • Unveiling the beta Pictoris system, coupling high contrast imaging, interferometric, and radial velocity data
  • 2020
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 642
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. The nearby and young beta Pictoris system hosts a well resolved disk, a directly imaged massive giant planet orbiting at similar or equal to 9 au, as well as an inner planet orbiting at similar or equal to 2.7 au, which was recently detected through radial velocity (RV). As such, it offers several unique opportunities for detailed studies of planetary system formation and early evolution.Aims. We aim to further constrain the orbital and physical properties of beta Pictoris b and c using a combination of high contrast imaging, long base-line interferometry, and RV data. We also predict the closest approaches or the transit times of both planets, and we constrain the presence of additional planets in the system.Methods. We obtained six additional epochs of SPHERE data, six additional epochs of GRAVITY data, and five additional epochs of RV data. We combined these various types of data in a single Markov-chain Monte Carlo analysis to constrain the orbital parameters and masses of the two planets simultaneously. The analysis takes into account the gravitational influence of both planets on the star and hence their relative astrometry. Secondly, we used the RV and high contrast imaging data to derive the probabilities of presence of additional planets throughout the disk, and we tested the impact of absolute astrometry.Results. The orbital properties of both planets are constrained with a semi-major axis of 9.8 0.4 au and 2.7 +/- 0.02 au for b and c, respectively, and eccentricities of 0.09 +/- 0.1 and 0.27 +/- 0.07, assuming the HIPPARCOS distance. We note that despite these low fitting error bars, the eccentricity of beta Pictoris c might still be over-estimated. If no prior is provided on the mass of beta Pictoris b, we obtain a very low value that is inconsistent with what is derived from brightness-mass models. When we set an evolutionary model motivated prior to the mass of beta Pictoris b, we find a solution in the 10-11 M-Jup range. Conversely, beta Pictoris c's mass is well constrained, at 7.8 +/- 0.4 M-Jup, assuming both planets are on coplanar orbits. These values depend on the assumptions on the distance of the beta Pictoris system. The absolute astrometry HIPPARCOS-Gaia data are consistent with the solutions presented here at the 2 sigma level, but these solutions are fully driven by the relative astrometry plus RV data. Finally, we derive unprecedented limits on the presence of additional planets in the disk. We can now exclude the presence of planets that are more massive than about 2.5 M-Jup closer than 3 au, and more massive than 3.5 M-Jup between 3 and 7.5 au. Beyond 7.5 au, we exclude the presence of planets that are more massive than 1-2 M-Jup.Conclusions. Combining relative astrometry and RVs allows one to precisely constrain the orbital parameters of both planets and to give lower limits to potential additional planets throughout the disk. The mass of beta Pictoris c is also well constrained, while additional RV data with appropriate observing strategies are required to properly constrain the mass of beta Pictoris b.
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  • Syed, J., et al. (författare)
  • The "Maggie" filament: Physical properties of a giant atomic cloud
  • 2022
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 657
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. The atomic phase of the interstellar medium plays a key role in the formation process of molecular clouds. Due to the line-of-sight confusion in the Galactic plane that is associated with its ubiquity, atomic hydrogen emission has been challenging to study. Aims. We investigate the physical properties of the "Maggie" filament, a large-scale filament identified in H I emission at line-of-sight velocities, upsilon(LSR) similar to -54 km s(-1). Methods. Employing the high-angular resolution data from The H I/OH Recombination line survey of the inner Milky Way (THOR), we have been able to study H I emission features at negative upsilon(LSR) velocities without any line-of-sight confusion due to the kinematic distance ambiguity in the first Galactic quadrant. In order to investigate the kinematic structure, we decomposed the emission spectra using the automated Gaussian fitting algorithm GAUSSPY+. Results. We identify one of the largest, coherent, mostly atomic H I filaments in the Milky Way. The giant atomic filament Maggie, with a total length of 1.2 +/- 0.1 kpc, is not detected in most other tracers, and it does not show signs of active star formation. At a kinematic distance of 17 kpc, Maggie is situated below (by approximate to 500 pc), but parallel to, the Galactic H I disk and is trailing the predicted location of the Outer Arm by 5-10 km s(-1) in longitude-velocity space. The centroid velocity exhibits a smooth gradient of less than +/- 3 km s(-1) (10 pc)(-1) and a coherent structure to within +/- 6 km s(-1). The line widths of similar to 10 km s(-1) along the spine of the filament are dominated by nonthermal effects. After correcting for optical depth effects, the mass of Maggie's dense spine is estimated to be 7.2(-1.9)(+2.5) x 10(5) M-circle dot. The mean number density of the filament is similar to 4 cm(-3), which is best explained by the filament being a mix of cold and warm neutral gas. In contrast to molecular filaments, the turbulent Mach number and velocity structure function suggest that Maggie is driven by transonic to moderately supersonic velocities that are likely associated with the Galactic potential rather than being subject to the effects of self-gravity or stellar feedback. The probability density function of the column density displays a log-normal shape around a mean of < N-HI > = 4.8 x 10(20) cm(-2), thus reflecting the absence of dominating effects of gravitational contraction. Conclusions. While Maggie's origin remains unclear, we hypothesize that Maggie could be the first in a class of atomic clouds that are the precursors of giant molecular filaments.
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19.
  • Tang, X. D., et al. (författare)
  • Kinetic temperature of massive star-forming molecular clumps measured with formaldehyde: IV. The ALMA view of N113 and N159W in the LMC
  • 2021
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 655
  • Tidskriftsartikel (refereegranskat)abstract
    • We mapped the kinetic temperature structure of two massive star-forming regions, N113 and N159W, in the Large Magellanic Cloud (LMC). We have used 1.6 (0.4 pc) resolution measurements of the para-H2CO JKaKc = 303-202, 322-221, and 321-220 transitions near 218.5 GHz to constrain RADEX non local thermodynamic equilibrium models of the physical conditions. The gas kinetic temperatures derived from the para-H2CO line ratios 322-221/303-202 and 321-220/303-202 range from 28 to 105 K in N113 and 29 to 68 K in N159W. Distributions of the dense gas traced by para-H2CO agree with those of the 1.3 mm dust and Spitzer 8.0 μm emission, but they do not significantly correlate with the Hα emission. The high kinetic temperatures (Tkin50 K) of the dense gas traced by para-H2CO appear to be correlated with the embedded infrared sources inside the clouds and/or young stellar objects in the N113 and N159W regions. The lower temperatures (Tkin < 50 K) were measured at the outskirts of the H2CO-bearing distributions of both N113 and N159W. It seems that the kinetic temperatures of the dense gas traced by para-H2CO are weakly affected by the external sources of the Hα emission. The non thermal velocity dispersions of para-H2CO are well correlated with the gas kinetic temperatures in the N113 region, implying that the higher kinetic temperature traced by para-H2CO is related to turbulence on a 0.4 pc scale. The dense gas heating appears to be dominated by internal star formation activity, radiation, and/or turbulence. It seems that the mechanism heating the dense gas of the star-forming regions in the LMC is consistent with that in Galactic massive star-forming regions located in the Galactic plane.
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20.
  • Wang, Y., et al. (författare)
  • Cloud formation in the atomic and molecular phase: H I self absorption (HISA) towards a giant molecular filament
  • 2020
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 634
  • Tidskriftsartikel (refereegranskat)abstract
    • Molecular clouds form from the atomic phase of the interstellar medium. However, characterizing the transition between the atomic and the molecular interstellar medium (ISM) is a complex observational task. Here we address cloud formation processes by combining HI self absorption (HISA) with molecular line data. Column density probability density functions (N-PDFs) are a common tool for examining molecular clouds. One scenario proposed by numerical simulations is that the N-PDF evolves from a log-normal shape at early times to a power-law-like shape at later times. To date, investigations of N-PDFs have been mostly limited to the molecular component of the cloud. In this paper, we study the cold atomic component of the giant molecular filament GMF38.1-32.4a (GMF38a, distance = 3.4 kpc, length similar to 230 pc), calculate its N-PDFs, and study its kinematics. We identify an extended HISA feature, which is partly correlated with the (CO)-C-13 emission. The peak velocities of the HISA and (CO)-C-13 observations agree well on the eastern side of the filament, whereas a velocity offset of approximately 4 km s(-1) is found on the western side. The sonic Mach number we derive from the linewidth measurements shows that a large fraction of the HISA, which is ascribed to the cold neutral medium (CNM), is at subsonic and transonic velocities. The column density of the CNM part is on the order of 10(20) to 10(21) cm(-2). The column density of molecular hydrogen, traced by (CO)-C-13, is an order of magnitude higher. The N-PDFs from HISA (CNM), HI emission (the warm and cold neutral medium), and (CO)-C-13 (molecular component) are well described by log-normal functions, which is in agreement with turbulent motions being the main driver of cloud dynamics. The N-PDF of the molecular component also shows a power law in the high column-density region, indicating self-gravity. We suggest that we are witnessing two different evolutionary stages within the filament. The eastern subregion seems to be forming a molecular cloud out of the atomic gas, whereas the western subregion already shows high column density peaks, active star formation, and evidence of related feedback processes.
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21.
  • Alcayne, V., et al. (författare)
  • A segmented total energy detector (sTED) for (n, gamma) cross section measurements at n_TOF EAR2
  • 2023
  • Ingår i: 15TH INTERNATIONAL CONFERENCE ON NUCLEAR DATA FOR SCIENCE AND TECHNOLOGY, ND2022. - : EDP Sciences.
  • Konferensbidrag (refereegranskat)abstract
    • The neutron time-of-flight facility n_TOF is characterised by its high instantaneous neutron intensity, high resolution and broad neutron energy spectra, specially conceived for neutron-induced reaction cross section measurements. Two Time-Of-Flight (TOR) experimental areas are available at the facility: experimental area 1 (EAR1), located at the end of the 185 m horizontal flight path from the spallation target, and experimental area 2 (EAR2), placed at 20 m from the target in the vertical direction. The neutron fluence in EAR2 is similar to 300 times more intense than in EARL in the relevant time-of-flight window. EAR2 was designed to carry out challenging cross-section measurements with low mass samples (approximately 1 mg), reactions with small cross-sections or/and highly radioactive samples. The high instantaneous fluence of EAR2 results in high counting rates that challenge the existing capture systems. Therefore, the sTED detector has been designed to mitigate these effects. In 2021, a dedicated campaign was done validating the performance of the detector up to at least 300 keV neutron energy. After this campaign, the detector has been used to perform various capture cross section measurements at n_TOF EAR2.
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22.
  • Backes, Claudia, et al. (författare)
  • Production and processing of graphene and related materials
  • 2020
  • Ingår i: 2D Materials. - : IOP Publishing. - 2053-1583. ; 7:2
  • Tidskriftsartikel (refereegranskat)abstract
    • We present an overview of the main techniques for production and processing of graphene and related materials (GRMs), as well as the key characterization procedures. We adopt a 'hands-on' approach, providing practical details and procedures as derived from literature as well as from the authors' experience, in order to enable the reader to reproduce the results. Section I is devoted to 'bottom up' approaches, whereby individual constituents are pieced together into more complex structures. We consider graphene nanoribbons (GNRs) produced either by solution processing or by on-surface synthesis in ultra high vacuum (UHV), as well carbon nanomembranes (CNM). Production of a variety of GNRs with tailored band gaps and edge shapes is now possible. CNMs can be tuned in terms of porosity, crystallinity and electronic behaviour. Section II covers 'top down' techniques. These rely on breaking down of a layered precursor, in the graphene case usually natural crystals like graphite or artificially synthesized materials, such as highly oriented pyrolythic graphite, monolayers or few layers (FL) flakes. The main focus of this section is on various exfoliation techniques in a liquid media, either intercalation or liquid phase exfoliation (LPE). The choice of precursor, exfoliation method, medium as well as the control of parameters such as time or temperature are crucial. A definite choice of parameters and conditions yields a particular material with specific properties that makes it more suitable for a targeted application. We cover protocols for the graphitic precursors to graphene oxide (GO). This is an important material for a range of applications in biomedicine, energy storage, nanocomposites, etc. Hummers' and modified Hummers' methods are used to make GO that subsequently can be reduced to obtain reduced graphene oxide (RGO) with a variety of strategies. GO flakes are also employed to prepare three-dimensional (3d) low density structures, such as sponges, foams, hydro- or aerogels. The assembly of flakes into 3d structures can provide improved mechanical properties. Aerogels with a highly open structure, with interconnected hierarchical pores, can enhance the accessibility to the whole surface area, as relevant for a number of applications, such as energy storage. The main recipes to yield graphite intercalation compounds (GICs) are also discussed. GICs are suitable precursors for covalent functionalization of graphene, but can also be used for the synthesis of uncharged graphene in solution. Degradation of the molecules intercalated in GICs can be triggered by high temperature treatment or microwave irradiation, creating a gas pressure surge in graphite and exfoliation. Electrochemical exfoliation by applying a voltage in an electrolyte to a graphite electrode can be tuned by varying precursors, electrolytes and potential. Graphite electrodes can be either negatively or positively intercalated to obtain GICs that are subsequently exfoliated. We also discuss the materials that can be amenable to exfoliation, by employing a theoretical data-mining approach. The exfoliation of LMs usually results in a heterogeneous dispersion of flakes with different lateral size and thickness. This is a critical bottleneck for applications, and hinders the full exploitation of GRMs produced by solution processing. The establishment of procedures to control the morphological properties of exfoliated GRMs, which also need to be industrially scalable, is one of the key needs. Section III deals with the processing of flakes. (Ultra)centrifugation techniques have thus far been the most investigated to sort GRMs following ultrasonication, shear mixing, ball milling, microfluidization, and wet-jet milling. It allows sorting by size and thickness. Inks formulated from GRM dispersions can be printed using a number of processes, from inkjet to screen printing. Each technique has specific rheological requirements, as well as geometrical constraints. The solvent choice is critical, not only for the GRM stability, but also in terms of optimizing printing on different substrates, such as glass, Si, plastic, paper, etc, all with different surface energies. Chemical modifications of such substrates is also a key step. Sections IV-VII are devoted to the growth of GRMs on various substrates and their processing after growth to place them on the surface of choice for specific applications. The substrate for graphene growth is a key determinant of the nature and quality of the resultant film. The lattice mismatch between graphene and substrate influences the resulting crystallinity. Growth on insulators, such as SiO2, typically results in films with small crystallites, whereas growth on the close-packed surfaces of metals yields highly crystalline films. Section IV outlines the growth of graphene on SiC substrates. This satisfies the requirements for electronic applications, with well-defined graphene-substrate interface, low trapped impurities and no need for transfer. It also allows graphene structures and devices to be measured directly on the growth substrate. The flatness of the substrate results in graphene with minimal strain and ripples on large areas, allowing spectroscopies and surface science to be performed. We also discuss the surface engineering by intercalation of the resulting graphene, its integration with Si-wafers and the production of nanostructures with the desired shape, with no need for patterning. Section V deals with chemical vapour deposition (CVD) onto various transition metals and on insulators. Growth on Ni results in graphitized polycrystalline films. While the thickness of these films can be optimized by controlling the deposition parameters, such as the type of hydrocarbon precursor and temperature, it is difficult to attain single layer graphene (SLG) across large areas, owing to the simultaneous nucleation/growth and solution/precipitation mechanisms. The differing characteristics of polycrystalline Ni films facilitate the growth of graphitic layers at different rates, resulting in regions with differing numbers of graphitic layers. High-quality films can be grown on Cu. Cu is available in a variety of shapes and forms, such as foils, bulks, foams, thin films on other materials and powders, making it attractive for industrial production of large area graphene films. The push to use CVD graphene in applications has also triggered a research line for the direct growth on insulators. The quality of the resulting films is lower than possible to date on metals, but enough, in terms of transmittance and resistivity, for many applications as described in section V. Transfer technologies are the focus of section VI. CVD synthesis of graphene on metals and bottom up molecular approaches require SLG to be transferred to the final target substrates. To have technological impact, the advances in production of high-quality large-area CVD graphene must be commensurate with those on transfer and placement on the final substrates. This is a prerequisite for most applications, such as touch panels, anticorrosion coatings, transparent electrodes and gas sensors etc. New strategies have improved the transferred graphene quality, making CVD graphene a feasible option for CMOS foundries. Methods based on complete etching of the metal substrate in suitable etchants, typically iron chloride, ammonium persulfate, or hydrogen chloride although reliable, are time- and resource-consuming, with damage to graphene and production of metal and etchant residues. Electrochemical delamination in a low-concentration aqueous solution is an alternative. In this case metallic substrates can be reused. Dry transfer is less detrimental for the SLG quality, enabling a deterministic transfer. There is a large range of layered materials (LMs) beyond graphite. Only few of them have been already exfoliated and fully characterized. Section VII deals with the growth of some of these materials. Amongst them, h-BN, transition metal tri- and di-chalcogenides are of paramount importance. The growth of h-BN is at present considered essential for the development of graphene in (opto) electronic applications, as h-BN is ideal as capping layer or substrate. The interesting optical and electronic properties of TMDs also require the development of scalable methods for their production. Large scale growth using chemical/physical vapour deposition or thermal assisted conversion has been thus far limited to a small set, such as h-BN or some TMDs. Heterostructures could also be directly grown. Section VIII discusses advances in GRM functionalization. A broad range of organic molecules can be anchored to the sp(2) basal plane by reductive functionalization. Negatively charged graphene can be prepared in liquid phase (e.g. via intercalation chemistry or electrochemically) and can react with electrophiles. This can be achieved both in dispersion or on substrate. The functional groups of GO can be further derivatized. Graphene can also be noncovalently functionalized, in particular with polycyclic aromatic hydrocarbons that assemble on the sp(2) carbon network by pi-pi stacking. In the liquid phase, this can enhance the colloidal stability of SLG/FLG. Approaches to achieve noncovalent on-substrate functionalization are also discussed, which can chemically dope graphene. Research efforts to derivatize CNMs are also summarized, as well as novel routes to selectively address defect sites. In dispersion, edges are the most dominant defects and can be covalently modified. This enhances colloidal stability without modifying the graphene basal plane. Basal plane point defects can also be modified, passivated and healed in ultra-high vacuum. The decoration of graphene with metal nanoparticles (NPs) has also received considerable attention, as it allows to exploit synergistic effects between NPs and graphene. Decoration can be either achieved chemically or in the gas phase. All LMs,
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23.
  • Carsten, Hobohm, et al. (författare)
  • Land Use Change and the Future of Biodiversity
  • 2021
  • Ingår i: Perspectives for Biodiversity and Ecosystems. - Cham : Springer. - 2214-2827 .- 2214-2835. - 9783030577094 ; , s. 451-483
  • Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
    • This synthesis report is a meta-analysis of perspectives for biodiversity and ecosystems, with a strong focus on human impacts on the environment, and a work order to enable and manage the protection, survival and evolution of all species on Earth. The goal is to protect nature without any further species loss (Zero Extinction). With this report, we assess alarming signals from the environment; determine the needs of threatened biota and the required actions to manage and protect landscapes and ecosystems; and identify some inescapable tendencies, challenges but also possibilities. The story of humans on Earth is at a critical juncture. Human behaviour is inherently dependent on physical and societal relations, including orientation and positioning within the physical environment. There is no single cultural benefit that is independent of provisioning through ecosystem services. Humans are part of the environment, acquire all needs from it and, as such, depend on its integrity and management for life and well-being. Moreover, if human impacts to the environment continue to increase the risk of rebound effects impacting human life and health will increase as well. Whenever a biome, ecosystem, habitat or species is heavily impacted or threatened with irreversible transformation or extinction, prevailing environmental conditions are relevant and should be observed, analysed and remedied as necessary and where possible. Ecology examines the evolutionary, historical and more recent interplay between biological life and the abiotic environment, while the role of social science and the humanities is to question the physical and social landscape, and how and why it should be protected or influenced, e.g. by nature conservation measures under political and economic, ethical and legal considerations. Thus, for all inter-relationships between natural and sociocultural processes, a joint venture in the form of social-ecological thinking is necessary to combine natural sciences and the humanities. With this contribution, we combine ecological knowledge with social science knowledge (s.l.) through the participation of scientists of many different disciplines. We analyse history and current processes to assess risks, threats and possibilities, and call for an array of regulations and measures that can contribute to halting of biodiversity loss and that assist in achieving a sustainable future. Regulations comprise creativity, cultural incentives, social norms, environmental education and economic investments—such as payments for sustainable agriculture, forestry, and fishery; investments in water, soil and air purity; and much clearer and stronger legal restrictions and consequences around waste streams and environmental degradation. Moreover, a gradual change from profit-oriented economies in the short-run to environmentally-sensitive policies that include systematic environmental programmes in the long term might help to decrease pressure on ecosystems and biota. Such economics might also include the real costs of consumerism, including the impacts of particular products on the environment and on human health. The greatest hurdle for the continued existence of many critically endangered species is the impact of widespread anthropogenic-driven change in the usage of water, air and land, and industry intensification in agriculture, aquaculture, forestry, urbanisation, transportation and mining sectors. However, there is not one simple solution to solve these issues. We conclude that many of the current developments have to be adjusted or gradually altered in a step-wise manner, especially with respect to existing sociocultural behaviours. Therefore, various concepts, decisions and measures should be discussed and implemented at all scales from local to supranational and among researchers, practitioners and politicians.
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24.
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25.
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26.
  • Franke, A., et al. (författare)
  • Operationalizing Ocean Health : Toward Integrated Research on Ocean Health and Recovery to Achieve Ocean Sustainability
  • 2020
  • Ingår i: One Earth. - : Elsevier BV. - 2590-3330 .- 2590-3322. ; 2:6, s. 557-565
  • Tidskriftsartikel (refereegranskat)abstract
    • Protecting the ocean has become a major goal of international policy as human activities increasingly endanger the integrity of the ocean ecosystem, often summarized as “ocean health.” By and large, efforts to protect the ocean have failed because, among other things, (1) the underlying socio-ecological pathways have not been properly considered, and (2) the concept of ocean health has been ill defined. Collectively, this prevents an adequate societal response as to how ocean ecosystems and their vital functions for human societies can be protected and restored. We review the confusion surrounding the term “ocean health” and suggest an operational ocean-health framework in line with the concept of strong sustainability. Given the accelerating degeneration of marine ecosystems, the restoration of regional ocean health will be of increasing importance. Our advocated transdisciplinary and multi-actor framework can help to advance the implementation of more active measures to restore ocean health and safeguard human health and well-being.
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27.
  • Garcia-Infantes, F., et al. (författare)
  • First high resolution measurement of neutron capture resonances in Yb-176 at the n_TOF CERN facility.
  • 2023
  • Ingår i: 15TH INTERNATIONAL CONFERENCE ON NUCLEAR DATA FOR SCIENCE AND TECHNOLOGY, ND2022. - : EDP Sciences.
  • Konferensbidrag (refereegranskat)abstract
    • Several international agencies recommend the study of new routes and new facilities for producing radioisotopes with application to nuclear medicine. Lu-177 is a versatile radioisotope used for therapy and diagnosis (theranostics) of cancer with good success in neuroendocrine tumours that is being studied to be applied to a wider range of tumours. Lu-177 is produced in few nuclear reactors mainly by the neutron capture on Lu-176. However, it could be produced at high -intensity accelerator-based neutron facilities. The energy of the neutrons in accelerator-based neutron facilities is higher than in thermal reactors. Thus, experimental data on the Yb-176(n,(sic)) cross-section in the eV and keV region are mandatory to calculate accurately the production of Yb-177, which beta decays to 177Lu. At present, there are not experimental data available from thermal to 3 keV of the Yb-176(n,(sic)) cross-section. In addition, there is no data in the resolved resonance region (RRR). This contribution shows the first results of the Yb-176 capture measurement performed at the n_TOF facility at CERN.
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28.
  • Hess, Timo, et al. (författare)
  • Dissecting the genetic heterogeneity of gastric cancer
  • 2023
  • Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 92
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Gastric cancer (GC) is clinically heterogenous according to location (cardia/non-cardia) and histopathology (diffuse/intestinal). We aimed to characterize the genetic risk architecture of GC according to its subtypes. Another aim was to examine whether cardia GC and oesophageal adenocarcinoma (OAC) and its precursor lesion Barrett's oesophagus (BO), which are all located at the gastro-oesophageal junction (GOJ), share polygenic risk architecture.Methods: We did a meta-analysis of ten European genome-wide association studies (GWAS) of GC and its subtypes. All patients had a histopathologically confirmed diagnosis of gastric adenocarcinoma. For the identification of risk genes among GWAS loci we did a transcriptome-wide association study (TWAS) and expression quantitative trait locus (eQTL) study from gastric corpus and antrum mucosa. To test whether cardia GC and OAC/BO share genetic aetiology we also used a European GWAS sample with OAC/BO.Findings: Our GWAS consisting of 5816 patients and 10,999 controls highlights the genetic heterogeneity of GC according to its subtypes. We newly identified two and replicated five GC risk loci, all of them with subtype-specific association. The gastric transcriptome data consisting of 361 corpus and 342 antrum mucosa samples revealed that an upregulated expression of MUC1, ANKRD50, PTGER4, and PSCA are plausible GC-pathomechanisms at four GWAS loci. At another risk locus, we found that the blood-group 0 exerts protective effects for non-cardia and diffuse GC, while blood-group A increases risk for both GC subtypes. Furthermore, our GWAS on cardia GC and OAC/BO (10,279 patients, 16,527 controls) showed that both cancer entities share genetic aetiology at the polygenic level and identified two new risk loci on the single-marker level.Interpretation: Our findings show that the pathophysiology of GC is genetically heterogenous according to location and histopathology. Moreover, our findings point to common molecular mechanisms underlying cardia GC and OAC/BO. 
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29.
  • Kohler, Andreas, Dr. rer. nat. 1988-, et al. (författare)
  • Early fate decision for mitochondrially encoded proteins by a molecular triage
  • 2023
  • Ingår i: Molecular Cell. - : Cell Press. - 1097-2765 .- 1097-4164. ; 83:19
  • Tidskriftsartikel (refereegranskat)abstract
    • Folding of newly synthesized proteins poses challenges for a functional proteome. Dedicated protein quality control (PQC) systems either promote the folding of nascent polypeptides at ribosomes or, if this fails, ensure their degradation. Although well studied for cytosolic protein biogenesis, it is not understood how these processes work for mitochondrially encoded proteins, key subunits of the oxidative phosphorylation (OXPHOS) system. Here, we identify dedicated hubs in proximity to mitoribosomal tunnel exits coordinating mitochondrial protein biogenesis and quality control. Conserved prohibitin (PHB)/m-AAA protease supercomplexes and the availability of assembly chaperones determine the fate of newly synthesized proteins by molecular triaging. The localization of these competing activities in the vicinity of the mitoribosomal tunnel exit allows for a prompt decision on whether newly synthesized proteins are fed into OXPHOS assembly or are degraded.
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30.
  • Koutoulaki, M., et al. (författare)
  • The GRAVITY young stellar object survey: IV. The CO overtone emission in 51 Oph at sub-au scales
  • 2021
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 645
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. 51 Oph is a Herbig Ae/Be star that exhibits strong near-infrared CO ro-vibrational emission at 2.3 μm, most likely originating in the innermost regions of a circumstellar disc. Aims. We aim to obtain the physical and geometrical properties of the system by spatially resolving the circumstellar environment of the inner gaseous disc. Methods. We used the second-generation Very Large Telescope Interferometer instrument GRAVITY to spatially resolve the continuum and the CO overtone emission. We obtained data over 12 baselines with the auxiliary telescopes and derive visibilities, and the differential and closure phases as a function of wavelength. We used a simple local thermal equilibrium ring model of the CO emission to reproduce the spectrum and CO line displacements. Results. Our interferometric data show that the star is marginally resolved at our spatial resolution, with a radius of ∼10.58 ± 2.65R·. The K-band continuum emission from the disc is inclined by 63° ± 1°, with a position angle of 116° ± 1°, and 4 ± 0.8 mas (0.5 ± 0.1 au) across. The visibilities increase within the CO line emission, indicating that the CO is emitted within the dust-sublimation radius. By modelling the CO bandhead spectrum, we derive that the CO is emitted from a hot (T = 1900-2800 K) and dense (NCO = (0.9-9) × 1021 cm-2) gas. The analysis of the CO line displacement with respect to the continuum allows us to infer that the CO is emitted from a region 0.10 ± 0.02 au across, well within the dust-sublimation radius. The inclination and position angle of the CO line emitting region is consistent with that of the dusty disc. Conclusions. Our spatially resolved interferometric observations confirm the CO ro-vibrational emission within the dust-free region of the inner disc. Conventional disc models exclude the presence of CO in the dust-depleted regions of Herbig AeBe stars. Ad hoc models of the innermost disc regions, that can compute the properties of the dust-free inner disc, are therefore required.
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31.
  • Miura, R.E., et al. (författare)
  • A giant molecular cloud catalogue in the molecular disc of the elliptical galaxy NGC 5128 (Centaurus A)
  • 2021
  • Ingår i: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 504:4, s. 6198-6215
  • Tidskriftsartikel (refereegranskat)abstract
    • We present the first census of giant molecular clouds (GMCs) complete down to 106 M⊙ and within the inner 4 kpc of the nearest giant elliptical and powerful radio galaxy, Centaurus A. We identified 689 GMCs using CO(1-0) data with 1 arcsec spatial resolution (∼20 pc) and 2 km s-1 velocity resolution obtained with the Atacama Large Millimeter/submillimeter Array. The I(CO)-N(H2) conversion factor based on the virial method is XCO = (2 ± 1) × 1020 cm-2(K km s-1)-1 for the entire molecular disc, consistent with that of the discs of spiral galaxies including the Milky Way, and XCO = (5 ± 2) × 1020 cm-2(K km s-1)-1 for the circumnuclear disc (CND; within a galactocentric radius of 200 pc). We obtained the GMC mass spectrum distribution and find that the best truncated power-law fit for the whole molecular disc, with index γ≃ -2.41 ± 0.02 and upper cut-off mass $\sim \! 1.3\times 10^{7}\, \mathrm{M}_{\odot }$, is also in agreement with that of nearby disc galaxies. A trend is found in the mass spectrum index from steep to shallow as we move to inner radii. Although the GMCs are in an elliptical galaxy, the general GMC properties in the molecular disc are as in spiral galaxies. However, in the CND, large offsets in the line-width-size scaling relations (∼0.3 dex higher than those in the GMCs in the molecular disc), a different XCO factor, and the shallowest GMC mass distribution shape (γ= -1.1 ± 0.2) all suggest that there the GMCs are most strongly affected by the presence of the active galactic nucleus and/or shear motions.
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32.
  • Mucciola, R., et al. (författare)
  • Neutron capture and total cross-section measurements on Mo-94'95'96 at n_TOF and GELINA
  • 2023
  • Ingår i: 15th International Conference on Nuclear Data for Science and Technology, ND2022. - : EDP Sciences.
  • Konferensbidrag (refereegranskat)abstract
    • Capture and total cross section measurements for 94'95'96 MO have been performed at the neutron time -of-flight facilities, n_TOF at CERN and GELINA at JRC-Geel. The measurements were performed using isotopically enriched samples with an enrichment above 95% for each of the (94'95'96)M0 isotopes. The capture measurements were performed at n_TOF using C6D6 detectors and a new sTED detector. The transmission measurements were performed at a 10 m station of GELINA using a Li-6 glass neutron detector. Preliminary results of these measurements are presented.
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33.
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34.
  • Pavon-Rodriguez, J. A., et al. (författare)
  • Characterisation of the n_TOF 20 m beam line at CERN with the new spallation target
  • 2023
  • Ingår i: 15TH INTERNATIONAL CONFERENCE ON NUCLEAR DATA FOR SCIENCE AND TECHNOLOGY, ND2022. - : EDP Sciences.
  • Konferensbidrag (refereegranskat)abstract
    • The n_TOF facility hosts CERN's pulsed neutron source, comprising two beam lines of different flight paths and one activation station. It is based on a proton beam delivered by the PS accelerator impinging on a lead spallation target. During Long Shutdown 2 (LS2) at CERN (2019-2021), a major upgrade of the spallation target was carried out in order to optimize the performances of the neutron beam. Therefore, the characteristics of n_TOF two experimental areas were investigated in detail. In this work, the focus is on the second experimental area (EAR2), located 20 m above the spallation target. Preliminary results of the neutron energy distribution and beam line energy resolution are presented, compared to previous experimental campaigns and Monte Carlo simulations with the FLUKA code. Moreover, preliminary results of the spatial beam profile measurements are shown.
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35.
  • Schwarz, Maria, et al. (författare)
  • Excessive copper impairs intrahepatocyte trafficking and secretion of selenoprotein P.
  • 2023
  • Ingår i: Nature communications. - 2041-1723. ; 14:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Selenium homeostasis depends on hepatic biosynthesis of selenoprotein P (SELENOP) and SELENOP-mediated transport from the liver to e.g. the brain. In addition, the liver maintains copper homeostasis. Selenium and copper metabolism are inversely regulated, as increasing copper and decreasing selenium levels are observed in blood during aging and inflammation. Here we show that copper treatment increased intracellular selenium and SELENOP in hepatocytes and decreased extracellular SELENOP levels. Hepatic accumulation of copper is a characteristic of Wilson's disease. Accordingly, SELENOP levels were low in serum of Wilson's disease patients and Wilson's rats. Mechanistically, drugs targeting protein transport in the Golgi complex mimicked some of the effects observed, indicating a disrupting effect of excessive copper on intracellular SELENOP transport resulting in its accumulation in the late Golgi. Our data suggest that hepatic copper levels determine SELENOP release from the liver and may affect selenium transport to peripheral organs such as the brain.
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36.
  • Škerlová, Jana, et al. (författare)
  • Structure of the native pyruvate dehydrogenase complex reveals the mechanism of substrate insertion
  • 2021
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The pyruvate dehydrogenase complex (PDHc) is a large multienzyme complex that converts pyruvate into acetyl-coenzyme A and in E. coli the core of the PDHc is formed by 24 copies of dihydrolipoyl transacetylase. Here, the authors present the cryo-EM structure of the E. coli dihydrolipoyl transacetylase 24-mer core in a native resting state including lipoyl domains, and discuss the mechanism of substrate shuttling by the lipoyl domains. The pyruvate dehydrogenase complex (PDHc) links glycolysis to the citric acid cycle by converting pyruvate into acetyl-coenzyme A. PDHc encompasses three enzymatically active subunits, namely pyruvate dehydrogenase, dihydrolipoyl transacetylase, and dihydrolipoyl dehydrogenase. Dihydrolipoyl transacetylase is a multidomain protein comprising a varying number of lipoyl domains, a peripheral subunit-binding domain, and a catalytic domain. It forms the structural core of the complex, provides binding sites for the other enzymes, and shuffles reaction intermediates between the active sites through covalently bound lipoyl domains. The molecular mechanism by which this shuttling occurs has remained elusive. Here, we report a cryo-EM reconstruction of the native E. coli dihydrolipoyl transacetylase core in a resting state. This structure provides molecular details of the assembly of the core and reveals how the lipoyl domains interact with the core at the active site.
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37.
  • Stamati, M. E., et al. (författare)
  • The n_TOF NEAR Station Commissioning and first physics case
  • 2023
  • Ingår i: 15TH INTERNATIONAL CONFERENCE ON NUCLEAR DATA FOR SCIENCE AND TECHNOLOGY, ND2022. - : EDP Sciences.
  • Konferensbidrag (refereegranskat)abstract
    • The NEAR Station is a new experimental area developed at the n_TOF Facility at CERN. The activation station of NEAR underwent a characterization of the beam following the installation of the new n_TOF Spallation Target. The commissioning of the neutron beam comprises a set of simulations made with the FLUKA code and experimental verification. The experimental determination of the neutron spectrum was made using activation techniques with three separate set-ups. Two set-ups were based on the Multi-foil Activation technique (MAM-1 and MAM-2), and the third set-up relied on the process of neutron moderation and activation of a single material (ANTILoPE). The three set-ups are presented. Also the present plans and future perspectives of the activation station of NEAR are discussed.
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38.
  • Tarrío, Diego, et al. (författare)
  • Neutron-induced fission cross sections of Th-232 and U-233 up to 1 GeV using parallel plate avalanche counters at the CERN n_TOF facility
  • 2023
  • Ingår i: Physical Review C. - : American Physical Society. - 2469-9985 .- 2469-9993. ; 107:4
  • Tidskriftsartikel (refereegranskat)abstract
    • The neutron-induced fission cross sections of Th-232 and U-233 were measured relative to U-235 in a wide neutron energy range up to 1 GeV (and from fission threshold in the case of Th-232, and from 0.7 eV in case of U-233), using the white-spectrum neutron source at the CERN Neutron Time-of-Flight (n_TOF) facility. Parallel plate avalanche counters (PPACs) were used, installed at the Experimental Area 1 (EAR1), which is located at 185 m from the neutron spallation target. The anisotropic emission of fission fragments were taken into account in the detection efficiency by using, in the case of U-233, previous results available in EXFOR, whereas in the case of Th-232 these data were obtained from our measurement, using PPACs and targets tilted 45 degrees with respect to the neutron beam direction. Finally, the obtained results are compared with past measurements and major evaluated nuclear data libraries. Calculations using the high-energy reaction models INCL++ and ABLA07 were performed and some of their parameters were modified to reproduce the experimental results. At high energies, where no other neutron data exist, our results are compared with experimental data on proton-induced fission. Moreover, the dependence of the fission cross section at 1 GeV with the fissility parameter of the target nucleus is studied by combining those ( p, f) data with our (n, f) data on Th-232 and U-233 and on other isotopes studied earlier at n_TOF using the same experimental setup.
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39.
  • Truedson, Petra, et al. (författare)
  • Monoaminoxidase inhibitors as a cause of serotonin syndrome : a systematic case review based on meta-analytic principles
  • 2021
  • Ingår i: European psychiatry. - : Cambridge University Press. - 0924-9338 .- 1778-3585. ; 64:S1, s. S361-S362
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Serotonin syndrome (SS) is a toxic state characterized by increased serotonin activity. It has been suggested that severe serotonin syndrome usually involves monoaminoxidase inhibitors (MAOIs).ObjectivesTo quantify in how far severe SS is associated with MAOIs.MethodsSystematic review and quantitative analysis of all SS cases published between 1 January 2004 and 31 December 2014. Severe SS was defined as cases, either requiring intensive care or resulting in death. Cases were included if they met the diagnostic criteria for SS according to at least one of the three diagnostic criteria systems (Hunter, Radomski and Sternbach).ResultsOf the 299 included cases, 118 (39%) met the definition for severe SS. Eight cases had insufficient information to enable severity classification. Of the severe cases, 48 (40%) involved a MAOI. Of these, 67% related to psychiatric MAOIs, such as phenelzine and moclobemide and 33% to a somatic MAOI, such as methylene blue and linezolid. Of the remaining 173 non-severe SS cases, 24 cases (13%) involved a MAOI. In these, 12% related to a psychiatric MAOI and 83% to a somatic MAOI. One case (4%) had a combination of both. The odds ratio for MAOI involvement in severe versus non-severe serotonin syndrome was 4.3 (CI 2.4 – 7.5; p < 0.001).ConclusionsIn the majority of published case reports, drugs other than MAOIs are involved in serotonin syndrome, even in severe cases. MAOIs are, however, more common in severe serotonin syndrome than in non-severe cases.Conflict of interestM. Ott: scientific advisory board member of Astra Zeneca, Sweden. U. Werneke: received funding for educational activities on behalf of Norrbotten Region; Astra Zeneca, Eli Lilly, Janssen, Novartis, Otsuka/Lundbeck, Servier, Shire, Sunovion. Others: None
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40.
  • Velsberg, Ott, et al. (författare)
  • Exploring smartness in public sector innovation : creating smart public services with the Internet of Things
  • 2020
  • Ingår i: European Journal of Information Systems. - : Taylor & Francis. - 0960-085X .- 1476-9344. ; 29:4, s. 350-368
  • Tidskriftsartikel (refereegranskat)abstract
    • The use of the term “smartness” in the context of public service delivery indicates an ambition of the public sector to become more agile and resilient through the adoption of emerging technologies. The Internet of Things (IoT) is an emerging technology that will be key to the realisation of smart public services. The research presented in this paper explored the role of IoT in public sector innovation through a qualitative study of how IoT technology can be leveraged to create and deliver smart winter road maintenance services. We use an existing smartness framework – based on the dimensions of efficiency, effectiveness, transparency and collaboration – to examine the consequences of introducing IoT-based innovation to road maintenance services. The findings suggest that IoT enables public sector innovation and that smartness is created through the combination of technology, people and organisations. The realisation of smartness in public sector innovation requires sufficient management capabilities and robust technology strategies, along with a willingness to explore and adopt new work practices rather than simply implement emerging technologies.
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41.
  • Velsberg, Ott, 1990- (författare)
  • In the age of IoT : exploring public sector smartness
  • 2021
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Smartness, which is emerging as a desirable attribute of governments, cities, and communities, has received heightened attention from researchers and practitioners. Smartness is a technology-centric view in which it is postulated that the public sector can become more resilient by adopting emergent technologies that improve efficiency, equality, citizen-centricity, transparency, collaboration, and security, thereby shaping the public sector to meet new demands and expectations. However, this novel technology carries several risks. The public sector may downplay the risks of implementing new technologies and the subsequent changes required for its transformation. Consequently, a more nuanced view is required to understand how the public sector can implement new emergent technologies. The Internet of Things (IoT) has been a significant force behind the push for smartness in the public sector. IoT is considered as the next radical evolution of the Internet towards a network of connected physical objects that enable interaction and data collection from the physical world, thereby providing data analytics and improving service delivery. Indeed, the development and use of IoT have exploded across the globe, affecting individuals and their interaction with their surroundings, as well as the manner in which businesses and governments operate. Unfortunately, limited information systems research on the transformational power of IoT technologies has been conducted. Therefore, it is necessary to understand how IoT can enable a smarter public sector. Although there is no doubt that IoT technologies can enable smart cities, the use of the technology by the public sector to reap the benefits thereof has not been studied sufficiently. The aim of this research is to offer insight into the use of IoT at the local government level and to conceptualise the created smartness.This dissertation consists of a cover paper and a collection of four research papers that are appended to the dissertation. Each research paper contributes to a better understanding of IoT, its applications, and its benefits for public sector smartness. Two multi-site case studies were conducted on IoT use within the public sector in Northern Europe to provide further insight.This research outlines the areas of IoT implementation in the public sector in Northern Europe. Several key application areas exist within the smart city sphere, in which IoT is widely used to enable smartness. Transportation and infrastructure are the most prevalent application areas for IoT, with more than half of the participating municipalities applying IoT. However, other areas of critical public services, such as education or care and support, lack IoT solutions. The findings demonstrate that the expected results and wide-scale IoT adoption differ significantly from the results of previous theoretical research, and that IoT systems do not meet public sector needs, particularly sectoral needs.The research concludes that the public sector is in its early stages of IoT implementation, namely exploring, prototyping, and piloting. Therefore, it is essential to provide solutions that satisfy the basic requirements of the public sector to support the use of IoT in the public sector and to transition towards smartness. However, this is complicated by the broad spectrum of conditions in which local governments find themselves, and no unique paradigm of smart city evolution exists. Furthermore, the study highlights the transformative potential of IoT in the public sector by identifying four distinct means by which IoT enables a smarter public sector: an increase in contextual awareness, the possibility of data-driven value creation, the reimagination of organisational structures, and innovation-oriented financing. The findings suggest that IoT enables smartness, provides both internal and external benefits, and is created through a combination of technology, people, and organisations. Furthermore, the smartness framework allows for the identification of the specific outcomes of applying emerging technologies to public services. Finally, this study demonstrates ethical perspectives relating to IoT in the public sector that must be considered and proposes means of addressing them. That is, it is proposed that it is crucial to concentrate on purpose limitation, data control, and data management to address the restrictions relating to ethics. In this manner, the study contributes to the discourse on ethics by suggesting practical methods for addressing ethical perspectives arising from IoT.
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42.
  • Velsberg, Ott, et al. (författare)
  • IoT Triggers : How municipalities are transforming to smarter cities through IoT use
  • 2021
  • Ingår i: Scandinavian Journal of Information Systems. - : IRIS Association. - 0905-0167 .- 1901-0990. ; 33:1, s. 17-64
  • Tidskriftsartikel (refereegranskat)abstract
    • The current digital transformation of society prompts the reshaping of both the private and public sectors and involves technology, organizations, and people. In this paper we explore within which application areas municipalities use IoT and how the implementation of IoT in this context triggers change and enables smarter cities. Based on an interview study of 337 municipalities in Denmark, Estonia, Finland, Norway and Sweden, our study portrays that the public sector is in its early stages of exploring IoT and reveals several application areas within the smart city sphere where new value has been created. Application of IoT was shown to trigger municipal digital transformation by increasing contextual awareness, enabling data-driven value creation, the reimagining of organizational structures, and innovation oriented financing. Such direct and indirect activities and practices were altogether shown to enable smarter cities. For the public sector to reap the benefits of potential digital transformation, it is however imperative to challenge current, and common, work practices. Otherwise, they risk getting caught up in incremental changes. Digital transformation involves radical changes, which in turn require technology to be fully integrated in processes and services and aligned with cultural expectations. Such changes require substantial support and commitment from stakeholders and a pronounced understanding of the value new and emerging technologies create.
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43.
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