| 1. |
- Abolins, M., et al.
(författare)
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The ATLAS Data Acquisition and High Level Trigger system
- 2016
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Ingår i: Journal of Instrumentation. - 1748-0221. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- This paper describes the data acquisition and high level trigger system of the ATLAS experiment at the Large Hadron Collider at CERN, as deployed during Run 1. Data flow as well as control, configuration and monitoring aspects are addressed. An overview of the functionality of the system and of its performance is presented and design choices are discussed.
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| 2. |
- Campbell, PJ, et al.
(författare)
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Pan-cancer analysis of whole genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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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. |
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| 4. |
- Bruzzi, M, et al.
(författare)
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Radiation-hard semiconductor detectors for SuperLHC
- 2005
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Ingår i: Nuclear Instruments & Methods in Physics Research. Section A: Accelerators, Spectrometers, Detectors, and Associated Equipment. - : Elsevier BV. - 0167-5087 .- 0168-9002. ; 541:1-2, s. 189-201
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Tidskriftsartikel (refereegranskat)abstract
- An option of increasing the luminosity of the Large Hadron Collider (LHC) at CERN to 1035 cm-2 s-1 has been envisaged to extend the physics reach of the machine. An efficient tracking down to a few centimetres from the interaction point will be required to exploit the physics potential of the upgraded LHC. As a consequence, the semiconductor detectors close to the interaction region will receive severe doses of fast hadron irradiation and the inner tracker detectors will need to survive fast hadron fluences of up to above 1016cm-2. The CERN-RD50 project "Development of Radiation Hard Semiconductor Devices for Very High Luminosity Colliders" has been established in 2002 to explore detector materials and technologies that will allow to operate devices up to, or beyond, this limit. The strategies followed by RD50 to enhance the radiation tolerance include the development of new or defect engineered detector materials (SiC, GaN, Czochralski and epitaxial silicon, oxygen enriched Float Zone silicon), the improvement of present detector designs and the understanding of the microscopic defects causing the degradation of the irradiated detectors. The latest advancements within the RD50 collaboration on radiation hard semiconductor detectors will be reviewed and discussed in this work.
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| 5. |
- Ahdida, C., et al.
(författare)
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Measurement of the muon flux from 400 GeV/c protons interacting in a thick molybdenum/tungsten target
- 2020
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Ingår i: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 80:3
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Tidskriftsartikel (refereegranskat)abstract
- The SHiP experiment is proposed to search for very weakly interacting particles beyond the Standard Model which are produced in a 400 GeV/c proton beam dump at the CERN SPS. About 1011muons per spill will be produced in the dump. To design the experiment such that the muon-induced background is minimized, a precise knowledge of the muon spectrum is required. To validate the muon flux generated by our Pythia and GEANT4 based Monte Carlo simulation (FairShip), we have measured the muon flux emanating from a SHiP-like target at the SPS. This target, consisting of 13 interaction lengths of slabs of molybdenum and tungsten, followed by a 2.4 m iron hadron absorber was placed in the H4 400 GeV/c proton beam line. To identify muons and to measure the momentum spectrum, a spectrometer instrumented with drift tubes and a muon tagger were used. During a 3-week period a dataset for analysis corresponding to (3.27 +/- 0.07)x1011protons on target was recorded. This amounts to approximatively 1% of a SHiP spill.
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| 6. |
- Ahdida, C., et al.
(författare)
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Sensitivity of the SHiP experiment to dark photons decaying to a pair of charged particles
- 2021
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Ingår i: European Physical Journal C. - : Springer Nature. - 1434-6044 .- 1434-6052. ; 81:5
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Tidskriftsartikel (refereegranskat)abstract
- Dark photons are hypothetical massive vector particles that could mix with ordinary photons. The simplest theoretical model is fully characterised by only two parameters: the mass of the dark photon m(gamma)D and its mixing parameter with the photon, epsilon. The sensitivity of the SHiP detector is reviewed for dark photons in the mass range between 0.002 and 10 GeV. Different productionmechanisms are simulated, with the dark photons decaying to pairs of visible fermions, including both leptons and quarks. Exclusion contours are presented and compared with those of past experiments. The SHiP detector is expected to have a unique sensitivity for m. D ranging between 0.8 and 3.3(-0.5)(+0.2) GeV, and epsilon(2) ranging between 10(-11) and 10(-17).
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| 7. |
- Ahdida, C., et al.
(författare)
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Sensitivity of the SHiP experiment to light dark matter
- 2021
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Ingår i: Journal of High Energy Physics (JHEP). - : Springer Nature. - 1126-6708 .- 1029-8479. ; :4
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Tidskriftsartikel (refereegranskat)abstract
- Dark matter is a well-established theoretical addition to the Standard Model supported by many observations in modern astrophysics and cosmology. In this context, the existence of weakly interacting massive particles represents an appealing solution to the observed thermal relic in the Universe. Indeed, a large experimental campaign is ongoing for the detection of such particles in the sub-GeV mass range. Adopting the benchmark scenario for light dark matter particles produced in the decay of a dark photon, with αD = 0.1 and mA′ = 3mχ, we study the potential of the SHiP experiment to detect such elusive particles through its Scattering and Neutrino detector (SND). In its 5-years run, corresponding to 2 · 1020 protons on target from the CERN SPS, we find that SHiP will improve the current limits in the mass range for the dark matter from about 1 MeV to 300 MeV. In particular, we show that SHiP will probe the thermal target for Majorana candidates in most of this mass window and even reach the Pseudo-Dirac thermal relic.
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| 8. |
- Ahdida, C., et al.
(författare)
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Track reconstruction and matching between emulsion and silicon pixel detectors for the SHiP-charm experiment
- 2022
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Ingår i: Journal of Instrumentation. - : IOP Publishing. - 1748-0221. ; 17:3
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Tidskriftsartikel (refereegranskat)abstract
- In July 2018 an optimization run for the proposed charm cross section measurement for SHiP was performed at the CERN SPS. A heavy, moving target instrumented with nuclear emulsion films followed by a silicon pixel tracker was installed in front of the Goliath magnet at the H4 proton beam-line. Behind the magnet, scintillating-fibre, drift-tube and RPC detectors were placed. The purpose of this run was to validate the measurement's feasibility, to develop the required analysis tools and fine-tune the detector layout. In this paper, we present the track reconstruction in the pixel tracker and the track matching with the moving emulsion detector. The pixel detector performed as expected and it is shown that, after proper alignment, a vertex matching rate of 87% is achieved.
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| 9. |
- Milstead, David A., et al.
(författare)
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The active muon shield in the SHiP experiment
- 2017
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Ingår i: Journal of Instrumentation. - 1748-0221. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- The SHiP experiment is designed to search for very weakly interacting particles beyond the Standard Model which are produced in a 400 GeV/c proton beam dump at the CERN SPS. An essential task for the experiment is to keep the Standard Model background level to less than 0.1 event after 2 x 10(20) protons on target. In the beam dump, around 10(11) muons will be produced per second. The muon rate in the spectrometer has to be reduced by at least four orders of magnitude to avoid muon-induced combinatorial background. A novel active muon shield is used to magnetically deflect the muons out of the acceptance of the spectrometer. This paper describes the basic principle of such a shield, its optimization and its performance.
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| 10. |
- Ahdida, C., et al.
(författare)
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The SHiP experiment at the proposed CERN SPS Beam Dump Facility
- 2022
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Ingår i: European Physical Journal C. - : Springer Nature. - 1434-6044 .- 1434-6052. ; 82:5
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Tidskriftsartikel (refereegranskat)abstract
- The Search for Hidden Particles (SHiP) Collaboration has proposed a general-purpose experimental facility operating in beam-dump mode at the CERN SPS accelerator to search for light, feebly interacting particles. In the baseline configuration, the SHiP experiment incorporates two complementary detectors. The upstream detector is designed for recoil signatures of light dark matter (LDM) scattering and for neutrino physics, in particular with tau neutrinos. It consists of a spectrometer magnet housing a layered detector system with high-density LDM/neutrino target plates, emulsion-film technology and electronic high-precision tracking. The total detector target mass amounts to about eight tonnes. The downstream detector system aims at measuring visible decays of feebly interacting particles to both fully reconstructed final states and to partially reconstructed final states with neutrinos, in a nearly background-free environment. The detector consists of a 50m\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\mathrm { \,m}$$\end{document} long decay volume under vacuum followed by a spectrometer and particle identification system with a rectangular acceptance of 5 m in width and 10 m in height. Using the high-intensity beam of 400GeV\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\,\mathrm {GeV}$$\end{document} protons, the experiment aims at profiting from the 4x1019\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$4\times 10<^>{19}$$\end{document} protons per year that are currently unexploited at the SPS, over a period of 5-10 years. This allows probing dark photons, dark scalars and pseudo-scalars, and heavy neutral leptons with GeV-scale masses in the direct searches at sensitivities that largely exceed those of existing and projected experiments. The sensitivity to light dark matter through scattering reaches well below the dark matter relic density limits in the range from a few MeV/c2\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\mathrm {\,MeV\!/}c<^>2}$$\end{document} up to 100 MeV-scale masses, and it will be possible to study tau neutrino interactions with unprecedented statistics. This paper describes the SHiP experiment baseline setup and the detector systems, together with performance results from prototypes in test beams, as it was prepared for the 2020 Update of the European Strategy for Particle Physics. The expected detector performance from simulation is summarised at the end.
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| 11. |
- Bradnam, K. R., et al.
(författare)
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Assemblathon 2 : Evaluating de novo methods of genome assembly in three vertebrate species
- 2013
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Ingår i: GigaScience. - : BioMed Central (BMC). - 2047-217X. ; 2:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The process of generating raw genome sequence data continues to become cheaper, faster, and more accurate. However, assembly of such data into high-quality, finished genome sequences remains challenging. Many genome assembly tools are available, but they differ greatly in terms of their performance (speed, scalability, hardware requirements, acceptance of newer read technologies) and in their final output (composition of assembled sequence). More importantly, it remains largely unclear how to best assess the quality of assembled genome sequences. The Assemblathon competitions are intended to assess current state-of-the-art methods in genome assembly. Results: In Assemblathon 2, we provided a variety of sequence data to be assembled for three vertebrate species (a bird, a fish, and snake). This resulted in a total of 43 submitted assemblies from 21 participating teams. We evaluated these assemblies using a combination of optical map data, Fosmid sequences, and several statistical methods. From over 100 different metrics, we chose ten key measures by which to assess the overall quality of the assemblies. Conclusions: Many current genome assemblers produced useful assemblies, containing a significant representation of their genes and overall genome structure. However, the high degree of variability between the entries suggests that there is still much room for improvement in the field of genome assembly and that approaches which work well in assembling the genome of one species may not necessarily work well for another.
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| 12. |
- Rajewsky, N., et al.
(författare)
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LifeTime and improving European healthcare through cell-based interceptive medicine
- 2020
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Ingår i: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 587:7834, s. 377-386
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Tidskriftsartikel (refereegranskat)abstract
- LifeTime aims to track, understand and target human cells during the onset and progression of complex diseases and their response to therapy at single-cell resolution. This mission will be implemented through the development and integration of single-cell multi-omics and imaging, artificial intelligence and patient-derived experimental disease models during progression from health to disease. Analysis of such large molecular and clinical datasets will discover molecular mechanisms, create predictive computational models of disease progression, and reveal new drug targets and therapies. Timely detection and interception of disease embedded in an ethical and patient-centered vision will be achieved through interactions across academia, hospitals, patient-associations, health data management systems and industry. Applying this strategy to key medical challenges in cancer, neurological, infectious, chronic inflammatory and cardiovascular diseases at the single-cell level will usher in cell-based interceptive medicine in Europe over the next decade.
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| 13. |
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| 14. |
- Ju, Young Seok, et al.
(författare)
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Somatic mutations reveal asymmetric cellular dynamics in the early human embryo
- 2017
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 543:7647, s. 714-718
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Tidskriftsartikel (refereegranskat)abstract
- Somatic cells acquire mutations throughout the course of an individual's life. Mutations occurring early in embryogenesis are often present in a substantial proportion of, but not all, cells in postnatal humans and thus have particular characteristics and effects. Depending on their location in the genome and the proportion of cells they are present in, these mosaic mutations can cause a wide range of genetic disease syndromes and predispose carriers to cancer. They have a high chance of being transmitted to offspring as de novo germline mutations and, in principle, can provide insights into early human embryonic cell lineages and their contributions to adult tissues. Although it is known that gross chromosomal abnormalities are remarkably common in early human embryos, our understanding of early embryonic somatic mutations is very limited. Here we use whole-genome sequences of normal blood from 241 adults to identify 163 early embryonic mutations. We estimate that approximately three base substitution mutations occur per cell per cell-doubling event in early human embryogenesis and these are mainly attributable to two known mutational signatures. We used the mutations to reconstruct developmental lineages of adult cells and demonstrate that the two daughter cells of many early embryonic cell-doubling events contribute asymmetrically to adult blood at an approximately 2:1 ratio. This study therefore provides insights into the mutation rates, mutational processes and developmental outcomes of cell dynamics that operate during early human embryogenesis.
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| 15. |
- Alexandrov, Ludmil B., et al.
(författare)
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Signatures of mutational processes in human cancer
- 2013
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 500:7463, s. 415-421
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Tidskriftsartikel (refereegranskat)abstract
- All cancers are caused by somatic mutations; however, understanding of the biological processes generating these mutations is limited. The catalogue of somatic mutations from a cancer genome bears the signatures of the mutational processes that have been operative. Here we analysed 4,938,362 mutations from 7,042 cancers and extracted more than 20 distinct mutational signatures. Some are present in many cancer types, notably a signature attributed to the APOBEC family of cytidine deaminases, whereas others are confined to a single cancer class. Certain signatures are associated with age of the patient at cancer diagnosis, known mutagenic exposures or defects in DNA maintenance, but many are of cryptic origin. In addition to these genome-wide mutational signatures, hypermutation localized to small genomic regions, 'kataegis', is found in many cancer types. The results reveal the diversity of mutational processes underlying the development of cancer, with potential implications for understanding of cancer aetiology, prevention and therapy.
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| 16. |
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| 17. |
- Nik-Zainal, Serena, et al.
(författare)
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Landscape of somatic mutations in 560 breast cancer whole-genome sequences
- 2016
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 534:7605, s. 47-54
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Tidskriftsartikel (refereegranskat)abstract
- We analysed whole-genome sequences of 560 breast cancers to advance understanding of the driver mutations conferring clonal advantage and the mutational processes generating somatic mutations. We found that 93 protein-coding cancer genes carried probable driver mutations. Some non-coding regions exhibited high mutation frequencies, but most have distinctive structural features probably causing elevated mutation rates and do not contain driver mutations. Mutational signature analysis was extended to genome rearrangements and revealed twelve base substitution and six rearrangement signatures. Three rearrangement signatures, characterized by tandem duplications or deletions, appear associated with defective homologous-recombination-based DNA repair: one with deficient BRCA1 function, another with deficient BRCA1 or BRCA2 function, the cause of the third is unknown. This analysis of all classes of somatic mutation across exons, introns and intergenic regions highlights the repertoire of cancer genes and mutational processes operating, and progresses towards a comprehensive account of the somatic genetic basis of breast cancer.
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| 18. |
- Baghdadchi, Amir, et al.
(författare)
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Effect of Ni content on 475°C embrittlement of directed energy deposited duplex stainless steel using a laser beam and wire feedstock
- 2024
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Ingår i: Materialia. - 2589-1529. ; 36
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Tidskriftsartikel (refereegranskat)abstract
- Duplex stainless steel (DSS), specifically the 2209 grade, is increasingly employed in additive manufacturing, particularly in processes like directed energy deposition using a laser beam with wire (DED-LB/w). However, a significant challenge arises when DSS faces brittleness within the temperature range of 250–500 °C. This study employs advanced characterization techniques, including atom probe tomography (APT) and transmission electron microscopy (TEM), to investigate DSS embrittlement after aging at 400 °C for up to 1000 h. The hardness analysis revealed that the higher Ni content in DED-LB/w-fabricated DSS cylinder promotes the age hardening compared to 2205 wrought DSS plate. Furthermore, APT and TEM demonstrated that, alongside the decomposition of ferrite into Fe-rich (α) and Cr-rich (αʹ) phases, clustering of Ni, Mn, and Si atoms contributes to the embrittlement. Although the Ni-Mn-Si-rich clusters could suggest nucleation of G-phase, the G-phase crystal structure was not observed by TEM. This might be attributed to the short aging time or limitations in the characterization technique. This work underscores the impact of characterization techniques on the measurement of spinodal decomposition, with APT providing capability of detecting nanometer sized clusters. By elucidating the complexities of 475 °C-embrittlement in DED-LB/w DSS, this study offers valuable insights for industrial applications and a deeper understanding of age hardening in duplex DSSs under specific manufacturing conditions.
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| 19. |
- Glodzik, Dominik, et al.
(författare)
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A somatic-mutational process recurrently duplicates germline susceptibility loci and tissue-specific super-enhancers in breast cancers
- 2017
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 49:3, s. 341-348
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Tidskriftsartikel (refereegranskat)abstract
- Somatic rearrangements contribute to the mutagenized landscape of cancer genomes. Here, we systematically interrogated rearrangements in 560 breast cancers by using a piecewise constant fitting approach. We identified 33 hotspots of large (>100 kb) tandem duplications, a mutational signature associated with homologous-recombination-repair deficiency. Notably, these tandem-duplication hotspots were enriched in breast cancer germline susceptibility loci (odds ratio (OR) = 4.28) and breast-specific 'super-enhancer' regulatory elements (OR = 3.54). These hotspots may be sites of selective susceptibility to double-strand-break damage due to high transcriptional activity or, through incrementally increasing copy number, may be sites of secondary selective pressure. The transcriptomic consequences ranged from strong individual oncogene effects to weak but quantifiable multigene expression effects. We thus present a somatic-rearrangement mutational process affecting coding sequences and noncoding regulatory elements and contributing a continuum of driver consequences, from modest to strong effects, thereby supporting a polygenic model of cancer development.
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| 20. |
- Goyal, Nitin, et al.
(författare)
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Medical Management vs Mechanical Thrombectomy for Mild Strokes: An International Multicenter Study and Systematic Review and Meta-analysis
- 2020
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Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149. ; 77:1, s. 16-24
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Tidskriftsartikel (refereegranskat)abstract
- © 2019 American Medical Association. All rights reserved. Importance: The benefit of mechanical thrombectomy (MT) in patients with stroke presenting with mild deficits (National Institutes of Health Stroke Scale [NIHSS] score <6) owing to emergency large-vessel occlusion (ELVO) remains uncertain. Objective: To assess the outcomes of patients with mild-deficits ELVO (mELVO) treated with MT vs best medical management (bMM). Data Sources: We retrospectively pooled patients with mELVO during a 5-year period from 16 centers. A meta-analysis of studies reporting efficacy and safety outcomes with MT or bMM among patients with mELVO was also conducted. Data were analyzed between 2013 and 2017. Study Selection: We identified studies that enrolled patients with stroke (within 24 hours of symptom onset) with mELVO treated with MT or bMM. Main Outcomes and Measures: Efficacy outcomes included 3-month favorable functional outcome and 3-month functional independence that were defined as modified Rankin Scale scores of 0 to 1 and 0 to 2, respectively. Safety outcomes included 3-month mortality and symptomatic and asymptomatic intracranial hemorrhage (ICH). Results: We evaluated a total of 251 patients with mELVO who were treated with MT (n = 138; 65 women; mean age, 65.2 years; median NIHSS score, 4; interquartile range [IQR], 3-5) or bMM (n = 113; 51 women; mean age, 64.8; median NIHSS score, 3; interquartile range [IQR], 2-4). The rate of asymptomatic ICH was lower in bMM (4.6% vs 17.5%; P =.002), while the rate of 3-month FI (after imputation of missing follow-up evaluations) was lower in MT (77.4% vs 88.5%; P =.02). The 2 groups did not differ in any other efficacy or safety outcomes. In multivariable analyses, MT was associated with higher odds of asymptomatic ICH (odds ratio [OR], 11.07; 95% CI, 1.31-93.53; P =.03). In the meta-analysis of 4 studies (843 patients), MT was associated with higher odds of symptomatic ICH in unadjusted analyses (OR, 5.52; 95% CI, 1.91-15.49; P =.002; I2 = 0%). This association did not retain its significance in adjusted analyses including 2 studies (OR, 2.06; 95% CI, 0.49-8.63; P =.32; I2 = 0%). The meta-analysis did not document any other independent associations between treatment groups and safety or efficacy outcomes. Conclusions and Relevance: Our multicenter study coupled with the meta-analysis suggests similar outcomes of MT and bMM in patients with stroke with mELVO, but no conclusions about treatment effect can be made. The clinical equipoise can further be resolved by a randomized clinical trial.
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| 22. |
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