| 1. |
- 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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| 4. |
- Villforth, C., et al.
(författare)
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Variability and stability in blazar jets on time-scales of years : optical polarization monitoring of OJ 287 in 2005-2009
- 2010
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 402:3, s. 2087-2111
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Tidskriftsartikel (refereegranskat)abstract
- OJ 287 is a BL Lac object at redshift z = 0.306 that has shown double-peaked bursts at regular intervals of similar to 12 yr during the last similar to 40 yr. We analyse optical photopolarimetric monitoring data from 2005 to 2009, during which the latest double-peaked outburst occurred. The aim of this study is twofold: firstly, we aim to analyse variability patterns and statistical properties of the optical polarization light curve. We find a strong preferred position angle in optical polarization. The preferred position angle can be explained by separating the jet emission into two components: an optical polarization core and chaotic jet emission. The optical polarization core is stable on time-scales of years and can be explained as emission from an underlying quiescent jet component. The chaotic jet emission sometimes exhibits a circular movement in the Stokes plane. We find six such events, all on the time-scales of 10-20 d. We interpret these events as a shock front moving forwards and backwards in the jet, swiping through a helical magnetic field. Secondly, we use our data to assess different binary black hole models proposed to explain the regularly appearing double-peaked bursts in OJ 287. We compose a list of requirements a model has to fulfil to explain the mysterious behaviour observed in OJ 287. The list includes not only characteristics of the light curve but also other properties of OJ 287, such as the black hole mass and restrictions on accretion flow properties. We rate all existing models using this list and conclude that none of the models is able to explain all observations. We discuss possible new explanations and propose a new approach to understanding OJ 287. We suggest that both the double-peaked bursts and the evolution of the optical polarization position angle could be explained as a sign of resonant accretion of magnetic field lines, a 'magnetic breathing' of the disc.
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| 5. |
- Gerstung, M, et al.
(författare)
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The evolutionary history of 2,658 cancers
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 122-
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Tidskriftsartikel (refereegranskat)abstract
- Cancer develops through a process of somatic evolution1,2. Sequencing data from a single biopsy represent a snapshot of this process that can reveal the timing of specific genomic aberrations and the changing influence of mutational processes3. Here, by whole-genome sequencing analysis of 2,658 cancers as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA)4, we reconstruct the life history and evolution of mutational processes and driver mutation sequences of 38 types of cancer. Early oncogenesis is characterized by mutations in a constrained set of driver genes, and specific copy number gains, such as trisomy 7 in glioblastoma and isochromosome 17q in medulloblastoma. The mutational spectrum changes significantly throughout tumour evolution in 40% of samples. A nearly fourfold diversification of driver genes and increased genomic instability are features of later stages. Copy number alterations often occur in mitotic crises, and lead to simultaneous gains of chromosomal segments. Timing analyses suggest that driver mutations often precede diagnosis by many years, if not decades. Together, these results determine the evolutionary trajectories of cancer, and highlight opportunities for early cancer detection.
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| 6. |
- Vogl, Gregory, et al.
(författare)
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Identification of machine tool geometric performance using on-machine inertial measurements
- 2017
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Ingår i: 6th International Conference on Virtual Machining Process Technology (VMPT 2017).
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Konferensbidrag (refereegranskat)abstract
- Machine tools degrade during operations, yet accurately detecting degradation of machine components such as linear axes is typically a manual and time-consuming process. Thus, manufacturers need automated and efficient methods to diagnose the condition of their machine tool linear axes with minimal disruptions to production. Towards this goal, a method was developed to use accelerometer and rate gyroscope data from an inertial measurement unit (IMU) for identification of changes in the translational and angular errors due to axis degradation. An IMU was created for application of the method on a machine tool. As a proof of concept for detection of translational error motions, IMU data was collected on a machine tool with experimentally simulated degradation; as the worktable moved along its nominal path, a cross-axis moved along a swept sinusoidal pattern with micrometer-level amplitudes. In another experiment, data was collected at three different locations on a worktable for the same axis motion. These experiments showed that the IMU detected micrometer-level and microradian-level degradation of linear axes, revealing that the IMU-based method is plausible for use in smart machine tools.
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| 7. |
- Vogl, Gregory W., et al.
(författare)
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Inertial Measurement Unit for On-Machine Diagnostics of Machine Tool Linear Axes
- 2016
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Konferensbidrag (refereegranskat)abstract
- Machine tools degrade during operations, yet knowledge of degradation is elusive; accurately detecting degradation of machines' components such as linear axes is typically a manual and time-consuming process. Thus, manufacturers need automated, efficient, and robust methods to diagnose the condition of their machine tool linear axes with minimal disruptions to production. Towards this end, a method was developed to use data from an inertial measurement unit (IMU) for identification of changes in the translational and angular errors due to axis degradation. The IMU-based method uses data from accelerometers and rate gyroscopes to identify changes in linear and angular errors due to axis degradation. A linear axis testbed, established for the purpose of verification and validation, revealed that the IMU-based method was capable of measuring geometric errors with acceptable test uncertainty ratios. Specifically, comparison of the IMU-based and laser-based results demonstrate that the IMU-based method is capable of detecting micrometer-level and microradian-level degradation of linear axes. Consequently, an IMU was created for application of the IMU-based method on a machine tool as a proof of concept for detection of linear axis error motions. If the data collection and analysis are integrated within a machine controller, the process may be streamlined for the optimization of maintenance activities and scheduling, supporting more intelligent decision-making by manufacturing personnel and the development of self-diagnosing smart machine tools.
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| 8. |
- Vogl, G. W., et al.
(författare)
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Identification of machine tools linear axes performance using on-machine embedded inertia measurement units
- 2017
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Ingår i: Laser Metrology and Machine Performance XII - 12th International Conference and Exhibition on Laser Metrology, Machine Tool, CMM and Robotic Performance, LAMDAMAP 2017. - : euspen. - 9780956679093 ; , s. 65-74
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Konferensbidrag (refereegranskat)abstract
- The current trend in manufacturing industry is from mass production towards flexible and adaptive manufacturing systems and cloud manufacturing. Self-learning machines and robot systems can play an essential role in the development of intelligent manufacturing systems and can be deployed to deal with a variety of tasks that can require flexibility and accuracy. However, in order for the machine tool (physical and control system) to deal with the desired task in a cognitive and efficient manner, the system must be "aware" of its capability and,most importantly,its limitations in order to avoid them and adjust itself to the desired task. Thus, characterization of machine tool accuracy and capability is necessary to realize that. In this study,data from a machine-embedded inertial measurement unit (IMU), consisting of accelerometers and rate gyroscopes,was used for identification of changes in linearand angular errormotions due to changes in operational conditionsor component degradation.The IMU-based results were validated against laser-based measurement results,demonstratingthat the IMU-based method is capable of detecting micrometer-level and microradian-level degradation of machine tool linearaxes.Thus, manufacturers could use themethod to efficientlyand robustly diagnose the condition of their machine tool linear axeswith minimal disruptions to production.
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| 9. |
- Yague-Fabra, Jose A., et al.
(författare)
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Scalability of precision design principles for machines and instruments
- 2021
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Ingår i: CIRP annals. - : Elsevier BV. - 0007-8506 .- 1726-0604. ; 70:2, s. 659-680
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Tidskriftsartikel (refereegranskat)abstract
- The implementation of precision engineering principles in the design of precision systems is fundamental to achieve high accuracy. Although these principles may be independent of the system working range, their implementation is not. The working range, the accuracy, and the load of the system limit, for instance, the selection of materials, the structural design, or the positioning system. This article analyzes the applicability of precision engineering design principles depending on the working range of the system in order to establish their scalability or lack of it in small, medium, and large range machines and instruments.
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