| 1. |
- Bott, Lukas Thomas, et al.
(författare)
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Coulomb dissociation of O-16 into He-4 and C-12
- 2023
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Ingår i: NUCLEAR PHYSICS IN ASTROPHYSICS - X, NPA-X 2022. - : EDP Sciences. - 2100-014X. ; 279
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Konferensbidrag (refereegranskat)abstract
- We measured the Coulomb dissociation of O-16 into He-4 and C-12 within the FAIR Phase-0 program at GSI Helmholtzzentrum fur Schwerionenforschung Darmstadt, Germany. From this we will extract the photon dissociation cross section O-16(alpha,gamma)C-12, which is the time reversed reaction to C-12(alpha,gamma)O-16. With this indirect method, we aim to improve on the accuracy of the experimental data at lower energies than measured so far. The expected low cross section for the Coulomb dissociation reaction and close magnetic rigidity of beam and fragments demand a high precision measurement. Hence, new detector systems were built and radical changes to the (RB)-B-3 setup were necessary to cope with the high-intensity O-16 beam. All tracking detectors were designed to let the unreacted O-16 ions pass, while detecting the C-12 and He-4.
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| 2. |
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| 3. |
- Boretzky, K., et al.
(författare)
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NeuLAND: The high-resolution neutron time-of-flight spectrometer for R 3 B at FAIR
- 2021
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Ingår i: Nuclear Instruments and Methods in Physics Research, Section A: Accelerators, Spectrometers, Detectors and Associated Equipment. - : Elsevier BV. - 0168-9002. ; 1014
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Tidskriftsartikel (refereegranskat)abstract
- NeuLAND (New Large-Area Neutron Detector) is the next-generation neutron detector for the R3B (Reactions with Relativistic Radioactive Beams) experiment at FAIR (Facility for Antiproton and Ion Research). NeuLAND detects neutrons with energies from 100 to 1000 MeV, featuring a high detection efficiency, a high spatial and time resolution, and a large multi-neutron reconstruction efficiency. This is achieved by a highly granular design of organic scintillators: 3000 individual submodules with a size of 5 × 5 × 250 cm3 are arranged in 30 double planes with 100 submodules each, providing an active area of 250 × 250 cm2 and a total depth of 3 m. The spatial resolution due to the granularity together with a time resolution of σt≤ 150 ps ensures high-resolution capabilities. In conjunction with calorimetric properties, a multi-neutron reconstruction efficiency of 50% to 70% for four-neutron events will be achieved, depending on both the emission scenario and the boundary conditions allowed for the reconstruction method. We present in this paper the final design of the detector as well as results from test measurements and simulations on which this design is based.
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| 4. |
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| 5. |
- George, Julie, et al.
(författare)
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Comprehensive genomic profiles of small cell lung cancer
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 524:7563, s. 47-U73
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Tidskriftsartikel (refereegranskat)abstract
- We have sequenced the genomes of 110 small cell lung cancers (SCLC), one of the deadliest human cancers. In nearly all the tumours analysed we found bi-allelic inactivation of TP53 and RB1, sometimes by complex genomic rearrangements. Two tumours with wild-type RB1 had evidence of chromothripsis leading to overexpression of cyclin D1 (encoded by the CCND1 gene), revealing an alternative mechanism of Rb1 deregulation. Thus, loss of the tumour suppressors TP53 and RB1 is obligatory in SCLC. We discovered somatic genomic rearrangements of TP73 that create an oncogenic version of this gene, TP73Dex2/3. In rare cases, SCLC tumours exhibited kinase gene mutations, providing a possible therapeutic opportunity for individual patients. Finally, we observed inactivating mutations in NOTCH family genes in 25% of human SCLC. Accordingly, activation of Notch signalling in a pre-clinical SCLC mouse model strikingly reduced the number of tumours and extended the survival of the mutant mice. Furthermore, neuroendocrine gene expression was abrogated by Notch activity in SCLC cells. This first comprehensive study of somatic genome alterations in SCLC uncovers several key biological processes and identifies candidate therapeutic targets in this highly lethal form of cancer.
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| 6. |
- Heil, M., et al.
(författare)
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A new Time-of-flight detector for the R 3 B setup
- 2022
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Ingår i: European Physical Journal A. - : Springer Science and Business Media LLC. - 1434-601X .- 1434-6001. ; 58:12
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Tidskriftsartikel (refereegranskat)abstract
- We present the design, prototype developments and test results of the new time-of-flight detector (ToFD) which is part of the R3B experimental setup at GSI and FAIR, Darmstadt, Germany. The ToFD detector is able to detect heavy-ion residues of all charges at relativistic energies with a relative energy precision σΔE/ ΔE of up to 1% and a time precision of up to 14 ps (sigma). Together with an elaborate particle-tracking system, the full identification of relativistic ions from hydrogen up to uranium in mass and nuclear charge is possible.
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| 7. |
- Huang, Miller, et al.
(författare)
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Engineering Genetic Predisposition in Human Neuroepithelial Stem Cells Recapitulates Medulloblastoma Tumorigenesis
- 2019
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Ingår i: Cell Stem Cell. - : CELL PRESS. - 1934-5909 .- 1875-9777. ; 25:3, s. 433-
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Tidskriftsartikel (refereegranskat)abstract
- Human neural stem cell cultures provide progenitor cells that are potential cells of origin for brain cancers. However, the extent to which genetic predisposition to tumor formation can be faithfully captured in stem cell lines is uncertain. Here, we evaluated neuroepithelial stem (NES) cells, representative of cerebellar progenitors. We transduced NES cells with MYCN, observing medulloblastoma upon orthotopic implantation in mice. Significantly, transcriptomes and patterns of DNA methylation from xenograft tumors were globally more representative of human medulloblastoma compared to a MYCN-driven genetically engineered mouse model. Orthotopic transplantation of NES cells generated from Gorlin syndrome patients, who are predis- posed to medulloblastoma due to germline-mutated PTCH1, also generated medulloblastoma. We engineered candidate cooperating mutations in Gorlin NES cells, with mutation of DDX3X or loss of GSE1 both accelerating tumorigenesis. These findings demonstrate that human NES cells provide a potent experimental resource for dissecting genetic causation in medulloblastoma.
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| 8. |
- Huthmann, Jens, et al.
(författare)
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Extending High-Level Synthesis with High-Performance Computing Performance Visualization
- 2020
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Ingår i: Proceedings - IEEE International Conference on Cluster Computing, ICCC. - : Institute of Electrical and Electronics Engineers (IEEE). ; , s. 371-380
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Konferensbidrag (refereegranskat)abstract
- The recent maturity in High-Level Synthesis (HLS) has renewed the interest of using Field-Programmable Gate-Arrays (FPGAs) to accelerate High-Performance Computing (HPC) applications. Today, several studies have shown performance-and power-benefits of using FPGAs compared to existing approaches for a number of application kernels with ample room for improvements. Unfortunately, modern HLS tools offer little support to gain clarity and insight regarding why a certain application behaves as it does on the FPGA, and most experts rely on intuition or abstract performance models. In this work, we hypothesize that existing profiling and visualization tools used in the HPC domain are also usable for understanding performance on FPGAs. We extend an existing HLS tool-chain to support Paraver-a state-of-the-art visualization and profiling tool well-known in HPC. We describe how each of the events and states are collected, and empirically quantify its hardware overhead. Finally, we practically apply our contribution to two different applications, demonstrating how the tool can be used to provide unique insights into application execution and how it can be used to guide optimizations. In this work, we hypothesize that existing profiling and visualization tools used in the HPC domain are also usable for understanding performance on FPGAs. We extend an existing HLS tool-chain to support Paraver-a state-of-the-art visualization and profiling tool well-known in HPC. We describe how each of the events and states are collected, and empirically quantify its hardware overhead. Finally, we practically apply our contribution to two different applications, demonstrating how the tool can be used to provide unique insights into application execution and how it can be used to guide optimizations.
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| 9. |
- Huthmann, Jens, et al.
(författare)
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Openmp device offloading to fpgas using the nymble infrastructure
- 2020
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Ingår i: Lect. Notes Comput. Sci.. - Cham : Springer Science and Business Media Deutschland GmbH. ; , s. 265-279
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Konferensbidrag (refereegranskat)abstract
- Next to GPUs, FPGAs are an attractive target for OpenMP device offloading, as they allow to implement highly efficient, applications-specific accelerators. However, prior approaches to support OpenMP device offloading for FPGAs have been limited by the interfaces provided by the FPGA vendors’ HLS tool interfaces or their integration with the OpenMP runtime, e.g., for data mapping. This work presents an approach to OpenMP device offloading for FPGAs based on the LLVM compiler infrastructure and the Nymble HLS compiler. The automatic compilation flow uses LLVM IR for HLS-specific optimizations and transformation and for the interaction with the Nymble HLS compiler. Parallel OpenMP constructs are automatically mapped to hardware threads executing simultaneously in the generated FPGA accelerator and the accelerator is integrated into libomptarget to support data-mapping. In a case study, we demonstrate the use of the compilation flow and evaluate its performance.
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| 10. |
- Mathey, Carina M, et al.
(författare)
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Molecular Genetic Screening in Patients With ACE Inhibitor/Angiotensin Receptor Blocker-Induced Angioedema to Explore the Role of Hereditary Angioedema Genes
- 2022
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Ingår i: Frontiers in Genetics. - : Frontiers Media S.A.. - 1664-8021. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Angioedema is a relatively rare but potentially life-threatening adverse reaction to angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs). As with hereditary forms of angioedema (HAE), this adverse reaction is mediated by bradykinin. Research suggests that ACEi/ARB-induced angioedema has a multifactorial etiology. In addition, recent case reports suggest that some ACEi/ARB-induced angioedema patients may carry pathogenic HAE variants. The aim of the present study was to investigate the possible association between ACEi/ARB-induced angioedema and HAE genes via systematic molecular genetic screening in a large cohort of ACEi/ARB-induced angioedema cases. Targeted re-sequencing of five HAE-associated genes (SERPING1, F12, PLG, ANGPT1, and KNG1) was performed in 212 ACEi/ARB-induced angioedema patients recruited in Germany/Austria, Sweden, and Denmark, and in 352 controls from a German cohort. Among patients, none of the identified variants represented a known pathogenic variant for HAE. Moreover, no significant association with ACEi/ARB-induced angioedema was found for any of the identified common [minor allele frequency (MAF) >5%] or rare (MAF < 5%) variants. However, several non-significant trends suggestive of possible protective effects were observed. The lowest p-value for an individual variant was found in PLG (rs4252129, p.R523W, p = 0.057, p.adjust > 0.999, Fisher's exact test). Variant p.R523W was found exclusively in controls and has previously been associated with decreased levels of plasminogen, a precursor of plasmin which is part of a pathway directly involved in bradykinin production. In addition, rare, potentially functional variants (MAF < 5%, Phred-scaled combined annotation dependent depletion score >10) showed a nominally significant enrichment in controls both: 1) across all five genes; and 2) in the F12 gene alone. However, these results did not withstand correction for multiple testing. In conclusion, our results suggest that HAE-associated mutations are, at best, a rare cause of ACEi/ARB-induced angioedema. Furthermore, we were unable to identify a significant association between ACEi/ARB-induced angioedema and other variants in the investigated genes. Further studies with larger sample sizes are warranted to draw more definite conclusions concerning variants with limited effect sizes, including protective variants.
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| 11. |
- Menétrey, Maxence, et al.
(författare)
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Targeted Additive Micromodulation of Grain Size in Nanocrystalline Copper Nanostructures by Electrohydrodynamic Redox 3D Printing
- 2022
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Ingår i: Small. - : Wiley. - 1613-6810 .- 1613-6829. ; 18:51
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Tidskriftsartikel (refereegranskat)abstract
- The control of materials’ microstructure is both a necessity and an opportunity for micro/nanometer-scale additive manufacturing technologies. On the one hand, optimization of purity and defect density of printed metals is a prerequisite for their application in microfabrication. On the other hand, the additive approach to materials deposition with highest spatial resolution offers unique opportunities for the fabrication of materials with complex, 3D graded composition or microstructure. As a first step toward both—optimization of properties and site-specific tuning of microstructure—an overview of the wide range of microstructure accessed in pure copper (up to >99.9 at.%) by electrohydrodynamic redox 3D printing is presented, and on-the-fly modulation of grain size in copper with smallest segments ≈400 nm in length is shown. Control of microstructure and materials properties by in situ adjustment of the printing voltage is demonstrated by variation of grain size by one order of magnitude and corresponding compression strength by a factor of two. Based on transmission electron microscopy and atom probe tomography, it is suggested that the small grain size is a direct consequence of intermittent solvent drying at the growth interface at low printing voltages, while larger grains are enabled by the permanent presence of solvent at higher potentials.
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| 12. |
- Pieber, Simone M., et al.
(författare)
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Analysis of regional CO2contributions at the high Alpine observatory Jungfraujoch by means of atmospheric transport simulations and δ13C
- 2022
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Ingår i: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 22:16, s. 10721-10749
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Tidskriftsartikel (refereegranskat)abstract
- In this study, we investigated the regional contributions of carbon dioxide (CO2) at the location of the high Alpine observatory Jungfraujoch (JFJ, Switzerland, 3580ĝ€¯mĝ€¯a.s.l.). To this purpose, we combined receptor-oriented atmospheric transport simulations for CO2 concentration in the period 2009-2017 with stable carbon isotope (δ13C-CO2) information. We applied two Lagrangian particle dispersion models driven by output from two different numerical weather prediction systems (FLEXPART-COSMO and STILT-ECMWF) in order to simulate CO2 concentration at JFJ based on regional CO2 fluxes, to estimate atmospheric δ13C-CO2, and to obtain model-based estimates of the mixed source signatures (δ13Cm). Anthropogenic fluxes were taken from a fuel-type-specific version of the EDGAR v4.3 inventory, while ecosystem fluxes were based on the Vegetation Photosynthesis and Respiration Model (VPRM). The simulations of CO2, δ13C-CO2, and δ13Cm were then compared to observations performed by quantum cascade laser absorption spectroscopy. The models captured around 40ĝ€¯% of the regional CO2 variability above or below the large-scale background and up to 35ĝ€¯% of the regional variability in δ13C-CO2. This is according to expectations considering the complex Alpine topography, the low intensity of regional signals at JFJ, and the challenging measurements. Best agreement between simulations and observations in terms of short-term variability and intensity of the signals for CO2 and δ13C-CO2 was found between late autumn and early spring. The agreement was inferior in the early autumn periods and during summer. This may be associated with the atmospheric transport representation in the models. In addition, the net ecosystem exchange fluxes are a possible source of error, either through inaccuracies in their representation in VPRM for the (Alpine) vegetation or through a day (uptake) vs. night (respiration) transport discrimination to JFJ. Furthermore, the simulations suggest that JFJ is subject to relatively small regional anthropogenic contributions due to its remote location (elevated and far from major anthropogenic sources) and the limited planetary boundary layer influence during winter. Instead, the station is primarily exposed to summertime ecosystem CO2 contributions, which are dominated by rather nearby sources (within 100ĝ€¯km). Even during winter, simulated gross ecosystem respiration accounted for approximately 50ĝ€¯% of all contributions to the CO2 concentrations above the large-scale background. The model-based monthly mean δ13Cm ranged from -ĝ€¯22ĝ€¯‰ in winter to -ĝ€¯28ĝ€¯‰ in summer and reached the most depleted values of -ĝ€¯35ĝ€¯‰ at higher fractions of natural gas combustion, as well as the most enriched values of -ĝ€¯17ĝ€¯‰ to -ĝ€¯12ĝ€¯‰ when impacted by cement production emissions. Observation-based δ13Cm values were derived independently from the simulations by a moving Keeling-plot approach. While model-based estimates spread in a narrow range, observation-based δ13Cm values exhibited a larger scatter and were limited to a smaller number of data points due to the stringent analysis prerequisites.
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| 13. |
- Reiser, Alain, et al.
(författare)
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Metals by Micro-Scale Additive Manufacturing : Comparison of Microstructure and Mechanical Properties
- 2020
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Ingår i: Advanced Functional Materials. - : Wiley. - 1616-301X .- 1616-3028. ; 30:28
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Tidskriftsartikel (refereegranskat)abstract
- Many emerging applications in microscale engineering rely on the fabrication of 3D architectures in inorganic materials. Small-scale additive manufacturing (AM) aspires to provide flexible and facile access to these geometries. Yet, the synthesis of device-grade inorganic materials is still a key challenge toward the implementation of AM in microfabrication. Here, a comprehensive overview of the microstructural and mechanical properties of metals fabricated by most state-of-the-art AM methods that offer a spatial resolution ≤10 μm is presented. Standardized sets of samples are studied by cross-sectional electron microscopy, nanoindentation, and microcompression. It is shown that current microscale AM techniques synthesize metals with a wide range of microstructures and elastic and plastic properties, including materials of dense and crystalline microstructure with excellent mechanical properties that compare well to those of thin-film nanocrystalline materials. The large variation in materials' performance can be related to the individual microstructure, which in turn is coupled to the various physico-chemical principles exploited by the different printing methods. The study provides practical guidelines for users of small-scale additive methods and establishes a baseline for the future optimization of the properties of printed metallic objects—a significant step toward the potential establishment of AM techniques in microfabrication.
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| 14. |
- Wolff, Christian M., et al.
(författare)
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Perfluorinated Self-Assembled Monolayers Enhance the Stability and Efficiency of Inverted Perovskite Solar Cells
- 2020
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Ingår i: ACS Nano. - : American Chemical Society (ACS). - 1936-0851 .- 1936-086X. ; 14:2, s. 1445-1456
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Tidskriftsartikel (refereegranskat)abstract
- Perovskite solar cells are among the most exciting photovoltaic systems as they combine low recombination losses, ease of fabrication, and high spectral tunability. The Achilles heel of this technology is the device stability due to the ionic nature of the perovskite crystal, rendering it highly hygroscopic, and the extensive diffusion of ions especially at increased temperatures. Herein, we demonstrate the application of a simple solution-processed perfluorinated self-assembled monolayer (p-SAM) that not only enhances the solar cell efficiency, but also improves the stability of the perovskite absorber and, in turn, the solar cell under increased temperature or humid conditions. The p-i-n-type perovskite devices employing these SAMs exhibited power conversion efficiencies surpassing 21%. Notably, the best performing devices are stable under standardized maximum power point operation at 85 °C in inert atmosphere (ISOS-L-2) for more than 250 h and exhibit superior humidity resilience, maintaining ∼95% device performance even if stored in humid air in ambient conditions over months (∼3000 h, ISOS-D-1). Our work, therefore, demonstrates a strategy towards efficient and stable perovskite solar cells with easily deposited functional interlayers.
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