| 61. |
- Jung, Martin, et al.
(author)
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Compensatory water effects link yearly global land CO 2 sink changes to temperature
- 2017
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 541:7638, s. 516-520
-
Journal article (peer-reviewed)abstract
- Large interannual variations in the measured growth rate of atmospheric carbon dioxide (CO 2) originate primarily from fluctuations in carbon uptake by land ecosystems. It remains uncertain, however, to what extent temperature and water availability control the carbon balance of land ecosystems across spatial and temporal scales. Here we use empirical models based on eddy covariance data and process-based models to investigate the effect of changes in temperature and water availability on gross primary productivity (GPP), terrestrial ecosystem respiration (TER) and net ecosystem exchange (NEE) at local and global scales. We find that water availability is the dominant driver of the local interannual variability in GPP and TER. To a lesser extent this is true also for NEE at the local scale, but when integrated globally, temporal NEE variability is mostly driven by temperature fluctuations. We suggest that this apparent paradox can be explained by two compensatory water effects. Temporal water-driven GPP and TER variations compensate locally, dampening water-driven NEE variability. Spatial water availability anomalies also compensate, leaving a dominant temperature signal in the year-to-year fluctuations of the land carbon sink. These findings help to reconcile seemingly contradictory reports regarding the importance of temperature and water in controlling the interannual variability of the terrestrial carbon balance. Our study indicates that spatial climate covariation drives the global carbon cycle response.
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| 62. |
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| 63. |
- Keppler, M., et al.
(author)
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Discovery of a planetary-mass companion within the gap of the transition disk around PDS 70
- 2018
-
In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 617
-
Journal article (peer-reviewed)abstract
- Context. Young circumstellar disks are the birthplaces of planets. Their study is of prime interest to understand the physical and chemical conditions under which planet formation takes place. Only very few detections of planet candidates within these disks exist, and most of them are currently suspected to be disk features.Aims. In this context, the transition disk around the young star PDS 70 is of particular interest, due to its large gap identified in previous observations, indicative of ongoing planet formation. We aim to search for the presence of an embedded young planet and search for disk structures that may be the result of disk-planet interactions and other evolutionary processes.Methods. We analyse new and archival near-infrared images of the transition disk PDS 70 obtained with the VLT/SPHERE, VLT/NaCo, and Gemini/NICI instruments in polarimetric differential imaging and angular differential imaging modes.Results. We detect a point source within the gap of the disk at about 195 mas (similar to 22 au) projected separation. The detection is confirmed at five different epochs, in three filter bands and using different instruments. The astrometry results in an object of bound nature, with high significance. The comparison of the measured magnitudes and colours to evolutionary tracks suggests that the detection is a companion of planetary mass. The luminosity of the detected object is consistent with that of an L-type dwarf, but its IR colours are redder, possibly indicating the presence of warm surrounding material. Further, we confirm the detection of a large gap of similar to 54 au in size within the disk in our scattered light images, and detect a signal from an inner disk component. We find that its spatial extent is very likely smaller than similar to 17 au in radius, and its position angle is consistent with that of the outer disk. The images of the outer disk show evidence of a complex azimuthal brightness distribution which is different at different wavelengths and may in part be explained by Rayleigh scattering from very small grains.Conclusions. The detection of a young protoplanet within the gap of the transition disk around PDS 70 opens the door to a so far observationally unexplored parameter space of planetary formation and evolution. Future observations of this system at different wavelengths and continuing astrometry will allow us to test theoretical predictions regarding planet-disk interactions, planetary atmospheres, and evolutionary models.
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| 64. |
- Keskin, Isil, et al.
(author)
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Effects of Cellular Pathway Disturbances on Misfolded Superoxide Dismutase-1 in Fibroblasts Derived from ALS Patients
- 2016
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:2
-
Journal article (peer-reviewed)abstract
- Mutations in superoxide dismutase-1 (SOD1) are a common known cause of amyotrophic lateral sclerosis (ALS). The neurotoxicity of mutant SOD1s is most likely caused by misfolded molecular species, but disease pathogenesis is still not understood. Proposed mechanisms include impaired mitochondrial function, induction of endoplasmic reticulum stress, reduction in the activities of the proteasome and autophagy, and the formation of neurotoxic aggregates. Here we examined whether perturbations in these cellular pathways in turn influence levels of misfolded SOD1 species, potentially amplifying neurotoxicity. For the study we used fibroblasts, which express SOD1 at physiological levels under regulation of the native promoter. The cells were derived from ALS patients expressing 9 different SOD1 mutants of widely variable molecular characteristics, as well as from patients carrying the GGGGCC-repeat-expansion in C9orf72 and from non-disease controls. A specific ELISA was used to quantify soluble, misfolded SOD1, and aggregated SOD1 was analysed by western blotting. Misfolded SOD1 was detected in all lines. Levels were found to be much lower in non-disease control and the non-SOD1 C9orf72 ALS lines. This enabled us to validate patient fibroblasts for use in subsequent perturbation studies. Mitochondrial inhibition, endoplasmic reticulum stress or autophagy inhibition did not affect soluble misfolded SOD1 and in most cases, detergent-resistant SOD1 aggregates were not detected. However, proteasome inhibition led to uniformly large increases in misfolded SOD1 levels in all cell lines and an increase in SOD1 aggregation in some. Thus the ubiquitin-proteasome pathway is a principal determinant of misfolded SOD1 levels in cells derived both from patients and controls and a decline in activity with aging could be one of the factors behind the mid-to late-life onset of inherited ALS.
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| 65. |
- Kliest, Tessa, et al.
(author)
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Clinical trials in pediatric ALS: a TRICALS feasibility study
- 2022
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In: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration. - : Taylor & Francis Group. - 2167-8421 .- 2167-9223. ; 23:7-8, s. 481-488
-
Journal article (peer-reviewed)abstract
- Background: Pediatric investigation plans (PIPs) describe how adult drugs can be studied in children. In 2015, PIPs for Amyotrophic Lateral Sclerosis (ALS) became mandatory for European marketing-authorization of adult treatments, unless a waiver is granted by the European Medicines Agency (EMA).Objective: To assess the feasibility of clinical studies on the effect of therapy in children (<18 years) with ALS in Europe.Methods: The EMA database was searched for submitted PIPs in ALS. A questionnaire was sent to 58 European ALS centers to collect the prevalence of pediatric ALS during the past ten years, the recruitment potential for future pediatric trials, and opinions of ALS experts concerning a waiver for ALS.Results: Four PIPs were identified; two were waived and two are planned for the future. In total, 49 (84.5%) centers responded to the questionnaire. The diagnosis of 44,858 patients with ALS was reported by 46 sites; 39 of the patients had an onset < 18 years (prevalence of 0.008 cases per 100,000 or 0.087% of all diagnosed patients). The estimated recruitment potential (47 sites) was 26 pediatric patients within five years. A majority of ALS experts (75.5%) recommend a waiver should apply for ALS due to the low prevalence of pediatric ALS.Conclusions: ALS with an onset before 18 years is extremely rare and may be a distinct entity from adult ALS. Conducting studies on the effect of disease-modifying therapy in pediatric ALS may involve lengthy recruitment periods, high costs, ethical/legal implications, challenges in trial design and limited information.
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| 66. |
- Klimek, Ludger, et al.
(author)
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In-vivo diagnostic test allergens in Europe : A call to action and proposal for recovery plan-An EAACI position paper
- 2020
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In: Allergy. European Journal of Allergy and Clinical Immunology. - : Wiley. - 0105-4538 .- 1398-9995. ; 75:9, s. 2161-2169
-
Journal article (peer-reviewed)abstract
- Diagnostic allergens are defined as medicinal products in the EU. Marketing authorization by national authorities is necessary; however, diagnostic allergens are not homogeneously regulated in different EU member states. Allergen manufacturers argue with increasing costs forcing them to continuously reduce the diagnostic allergen portfolios offered to allergists. In contrast, EAACI and national European Allergy Societies see the need for the availability of a wide range of high‐quality diagnostic allergens for in vivo diagnosis of IgE‐mediated allergies not only covering predominant but also less frequent allergen sources. In a recent EAACI task force survey, the current practice of allergy diagnosis was shown to rely on skin tests as first option in almost 2/3 of all types of allergic diseases and in 90% regarding respiratory allergies.With the need to ensure the availability of high‐quality diagnostic allergens in the EU, an action plan has been set up by EAACI to analyse the current regulatory demands in EU member states and to define possible solutions stated in this document: (a) simplification of authorization for diagnostic allergens; (b) specific regulation of special types of diagnostic allergens; (c) new models beyond the current model of homologous groups; (d) simplification of pharmacovigilance reporting; (e) reduction of regulation fees for diagnostic allergens; (f) reimbursement for diagnostic allergens.Joining forces of allergists, manufacturers and authorities are of high importance to ensure remaining relevant allergens in the EU markets to facilitate a sustainable and comprehensive service for the diagnosis and treatment of allergic diseases.
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| 67. |
- Kraemer, Bernhard K., et al.
(author)
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Tacrolimus-Based, Steroid-Free Regimens in Renal Transplantation : 3-Year Follow-Up of the ATLAS Trial
- 2012
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In: Transplantation. - 0041-1337 .- 1534-6080. ; 94:5, s. 492-498
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Journal article (peer-reviewed)abstract
- Background. Long-term use of corticosteroids is associated with considerable morbidity, including cardiovascular and metabolic adverse effects. Methods. This study evaluated the long-term efficacy and safety of two steroid-free regimens compared with a triple immunosuppressive therapy in renal transplant recipients. This was a 3-year follow-up to a 6-month, open-label, randomized, multicenter study. Results. Data from 3 years were available for 421 (93.3%) of 451 patients in the original intent-to-treat population (143 tacrolimus/basiliximab [Tac/Bas], 139 tacrolimus/mycophenolate mofetil [Tac/MMF], and 139 tacrolimus/MMF/steroids [triple therapy]). In the time interval from 6 months to 3 years after transplantation, the incidence of biopsy-proven acute rejection was low and similar (Tac/Bas, 2.1%; Tac/MMF, 2.2%; triple therapy, 2.2%); Most rejection episodes occurred during the first 6 months of the study. Graft survival was high (Kaplan-Meier estimates: 92.7%, 92.5%, and 92.5%), as was patient survival (93.1%, 96.4%, and 97.0%). There were 10 graft losses (n=2, 4, and 4) and 12 patient deaths (n=5, 2, and 5). Renal function was well preserved throughout the study and similar between groups. There was a trend toward improved cardiovascular risk factors in the Tac/Bas group, including reduced total and low-density lipoprotein cholesterol and lower new-onset insulin use. There were no between-group differences in the incidence or type of adverse events. Conclusion. Higher rates of acute rejection early in treatment were seen with the steroid-free regimens, but this did not translate into poorer long-term outcomes, such as graft and patient survival and renal function. A trend for a more favorable cardiovascular risk profile was observed for steroid-free immunosuppression with Tac/Bas.
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| 68. |
- Krämer, Bernhard K., et al.
(author)
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Tacrolimus combined with two different corticosteroid-free regimens compared with a standard triple regimen in renal transplantation : one year observational results
- 2010
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In: Clinical Transplantation. - : Wiley. - 0902-0063 .- 1399-0012. ; 24:1, s. E1-E9
-
Journal article (peer-reviewed)abstract
- Side effects of steroid use have led to efforts to minimize their use in transplantation. Two corticosteroid-free regimens were compared with a triple immunosuppressive therapy. Data from the original intent-to-treat (ITT) population (153 tacrolimus/basiliximab [Tac/Bas], 151 tacrolimus/MMF [Tac/MMF], and 147 tacrolimus/MMF/steroids [control]) were analyzed in a 12-month follow-up. Percentage of graft survival were 92.8%, 95.4%, and 95.9% (KM estimates 89.9%, 95.3%, 95.9%), percentage of surviving patients were 98.7%, 98.0%, and 100% (KM estimates 95.9%, 92.8%, and 100%). During months 7-12, graft loss occurred in 3 Tac/Bas, 2 Tac/MMF, and zero control patients, patient deaths in 1 Tac/Bas, 2 Tac/MMF, and zero control, and biopsy-proven acute rejection episodes in 4 Tac/Bas, 3 Tac/MMF, and zero control. Mean serum creatinine at month 12 was 141.9 +/- 69.6 muM, 144.0 +/- 82.1 muM, and 134.5 +/- 71.2 muM (ns). New-onset insulin use in previously non-diabetic patients at month 12 was 1/138, 6/127, and 4/126. Patient and graft survival as well as renal function at 12 months were not different between patient groups, despite considerably higher rates of acute rejection occurring within the first six months after transplantation in both steroid-free patient groups. Tac/Bas therapy might offer benefits in terms of a trend for a more favorable cardiovascular risk profile.
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| 69. |
- Lagrange, A. -M., et al.
(author)
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A narrow, edge-on disk resolved around HD 106906 with SPHERE
- 2016
-
In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 586
-
Journal article (peer-reviewed)abstract
- Context. HD 106906AB is the only young binary system so far around which a planet has been imaged and a debris disk has been shown to exist, thanks to a strong IR excess. As such, it represents a unique opportunity for studying the dynamics of young planetary systems. Aims. We aim at further investigating the close (tens of au scales) environment of the HD 106906AB system. Methods. We used the extreme adaptive-optics-fed, high-contrast imager SPHERE that has recently been installed on the VLT to observe HD 106906. Both the IRDIS imager and the Integral Field Spectrometer were used. Results. We discovered a highly inclined, ring-like disk at a distance of 65 au from the star. The disk shows a strong brightness asymmetry with respect to its semi-major axis. It shows a smooth outer edge, compatible with ejection of small grains by the stellar radiation pressure. We show furthermore that the planet's projected position is significantly above the PA of the disk. Given the determined disk inclination, it is not excluded, however, that the planet could still orbit within the disk plane if at a large separation (2000 3000 au). We identified several additional point sources in the SPHERE /IRDIS field of view that appear to be background objects. We compare this system with other debris disks sharing similarities, and we briefly discuss the present results in the framework of dynamical evolution.
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| 70. |
- Langlois, M., et al.
(author)
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First scattered light detection of a nearly edge-on transition disk around the T Tauri star RY Lupi
- 2018
-
In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 614
-
Journal article (peer-reviewed)abstract
- Context. Transition disks are considered sites of ongoing planet formation, and their dust and gas distributions could be signposts of embedded planets. The transition disk around the T Tauri star RY Lup has an inner dust cavity and displays a strong silicate emission feature. Aims. Using high-resolution imaging we study the disk geometry, including non-axisymmetric features, and its surface dust grain, to gain a better understanding of the disk evolutionary process. Moreover, we search for companion candidates, possibly connected to the disk. Methods. We obtained high-contrast and high angular resolution data in the near-infrared with the VLT/SPHERE extreme adaptive optics instrument whose goal is to study the planet formation by detecting and characterizing these planets and their formation environments through direct imaging. We performed polarimetric imaging of the RY Lup disk with IRDIS (at 1.6 mu m), and obtained intensity images with the IRDIS dual-band imaging camera simultaneously with the IFS spectro-imager (0.9-1.3 mu m). Results. We resolved for the first time the scattered light from the nearly edge-on circumstellar disk around RY Lup, at projected separations in the 100 au range. The shape of the disk and its sharp features are clearly detectable at wavelengths ranging from 0.9 to 1.6 mu m. We show that the observed morphology can be interpreted as spiral arms in the disk. This interpretation is supported by in-depth numerical simulations. We also demonstrate that these features can be produced by one planet interacting with the disk. We also detect several point sources which are classified as probable background objects.
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