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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. |
- Aartsen, M. G., et al.
(författare)
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Development of an analysis to probe the neutrino mass ordering with atmospheric neutrinos using three years of IceCube DeepCore data IceCube Collaboration
- 2020
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Ingår i: European Physical Journal C. - : SPRINGER. - 1434-6044 .- 1434-6052. ; 80:1
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Tidskriftsartikel (refereegranskat)abstract
- The Neutrino Mass Ordering (NMO) remains one of the outstanding questions in the field of neutrino physics. One strategy to measure the NMO is to observe matter effects in the oscillation pattern of atmospheric neutrinos above similar to 1GeV, as proposed for several next-generation neutrino experiments. Moreover, the existing IceCube DeepCore detector can already explore this type of measurement. We present the development and application of two independent analyses to search for the signature of the NMO with three years of DeepCore data. These analyses include a full treatment of systematic uncertainties and a statistically-rigorous method to determine the significance for the NMO from a fit to the data. Both analyses show that the dataset is fully compatible with both mass orderings. For the more sensitive analysis, we observe a preference for normal ordering with a p-value of pIO=15.3% and CLs=53.3% for the inverted ordering hypothesis, while the experimental results from both analyses are consistent within their uncertainties. Since the result is independent of the value of delta CP and obtained from energies E nu greater than or similar to 5GeV, it is complementary to recent results from long-baseline experiments. These analyses set the groundwork for the future of this measurement with more capable detectors, such as the IceCube Upgrade and the proposed PINGU detector.
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| 4. |
- Aartsen, M. G., et al.
(författare)
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Neutrinos below 100 TeV from the southern sky employing refined veto techniques to IceCube data
- 2020
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Ingår i: Astroparticle physics. - : ELSEVIER. - 0927-6505 .- 1873-2852. ; 116
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Tidskriftsartikel (refereegranskat)abstract
- Many Galactic sources of gamma rays, such as supernova remnants, are expected to produce neutrinos with a typical energy cutoff well below 100 TeV. For the IceCube Neutrino Observatory located at the South Pole, the southern sky, containing the inner part of the Galactic plane and the Galactic Center, is a particularly challenging region at these energies, because of the large background of atmospheric muons. In this paper, we present recent advancements in data selection strategies for track-like muon neutrino events with energies below 100 TeV from the southern sky. The strategies utilize the outer detector regions as veto and features of the signal pattern to reduce the background of atmospheric muons to a level which, for the first time, allows IceCube searching for point-like sources of neutrinos in the southern sky at energies between 100 GeV and several TeV in the muon neutrino charged current channel. No significant clustering of neutrinos above background expectation was observed in four years of data recorded with the completed IceCube detector. Upper limits on the neutrino flux for a number of spectral hypotheses are reported for a list of astrophysical objects in the southern hemisphere.
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| 5. |
- Beal, Jacob, et al.
(författare)
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Robust estimation of bacterial cell count from optical density
- 2020
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 8. |
- De Leoz, M. L. A., et al.
(författare)
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NIST Interlaboratory Study on Glycosylation Analysis of Monoclonal Antibodies: Comparison of Results from Diverse Analytical Methods
- 2020
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Ingår i: Molecular & Cellular Proteomics. - 1535-9476. ; 19:1, s. 11-30
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Tidskriftsartikel (refereegranskat)abstract
- A broad-based interlaboratory study of glycosylation profiles of a reference and modified IgG antibody involving 103 reports from 76 laboratories. Glycosylation is a topic of intense current interest in the development of biopharmaceuticals because it is related to drug safety and efficacy. This work describes results of an interlaboratory study on the glycosylation of the Primary Sample (PS) of NISTmAb, a monoclonal antibody reference material. Seventy-six laboratories from industry, university, research, government, and hospital sectors in Europe, North America, Asia, and Australia submitted a total of 103 reports on glycan distributions. The principal objective of this study was to report and compare results for the full range of analytical methods presently used in the glycosylation analysis of mAbs. Therefore, participation was unrestricted, with laboratories choosing their own measurement techniques. Protein glycosylation was determined in various ways, including at the level of intact mAb, protein fragments, glycopeptides, or released glycans, using a wide variety of methods for derivatization, separation, identification, and quantification. Consequently, the diversity of results was enormous, with the number of glycan compositions identified by each laboratory ranging from 4 to 48. In total, one hundred sixteen glycan compositions were reported, of which 57 compositions could be assigned consensus abundance values. These consensus medians provide community-derived values for NISTmAb PS. Agreement with the consensus medians did not depend on the specific method or laboratory type. The study provides a view of the current state-of-the-art for biologic glycosylation measurement and suggests a clear need for harmonization of glycosylation analysis methods.
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| 9. |
- Kim, Jae-Young, et al.
(författare)
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Event Horizon Telescope imaging of the archetypal blazar 3C 279 at an extreme 20 microarcsecond resolution
- 2020
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 640
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Tidskriftsartikel (refereegranskat)abstract
- 3C 279 is an archetypal blazar with a prominent radio jet that show broadband flux density variability across the entire electromagnetic spectrum. We use an ultra-high angular resolution technique - global Very Long Baseline Interferometry (VLBI) at 1.3mm (230 GHz) - to resolve the innermost jet of 3C 279 in order to study its fine-scale morphology close to the jet base where highly variable-ray emission is thought to originate, according to various models. The source was observed during four days in April 2017 with the Event Horizon Telescope at 230 GHz, including the phased Atacama Large Millimeter/submillimeter Array, at an angular resolution of ∼20 μas (at a redshift of z = 0:536 this corresponds to ∼0:13 pc ∼ 1700 Schwarzschild radii with a black hole mass MBH = 8 × 108 M⊙). Imaging and model-fitting techniques were applied to the data to parameterize the fine-scale source structure and its variation.We find a multicomponent inner jet morphology with the northernmost component elongated perpendicular to the direction of the jet, as imaged at longer wavelengths. The elongated nuclear structure is consistent on all four observing days and across diffierent imaging methods and model-fitting techniques, and therefore appears robust. Owing to its compactness and brightness, we associate the northern nuclear structure as the VLBI "core". This morphology can be interpreted as either a broad resolved jet base or a spatially bent jet.We also find significant day-to-day variations in the closure phases, which appear most pronounced on the triangles with the longest baselines. Our analysis shows that this variation is related to a systematic change of the source structure. Two inner jet components move non-radially at apparent speeds of ∼15 c and ∼20 c (∼1:3 and ∼1:7 μas day-1, respectively), which more strongly supports the scenario of traveling shocks or instabilities in a bent, possibly rotating jet. The observed apparent speeds are also coincident with the 3C 279 large-scale jet kinematics observed at longer (cm) wavelengths, suggesting no significant jet acceleration between the 1.3mm core and the outer jet. The intrinsic brightness temperature of the jet components are ≤1010 K, a magnitude or more lower than typical values seen at ≥7mm wavelengths. The low brightness temperature and morphological complexity suggest that the core region of 3C 279 becomes optically thin at short (mm) wavelengths.
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| 10. |
- Aghanim, N., et al.
(författare)
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Planck 2018 results I. Overview and the cosmological legacy of Planck
- 2020
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 641
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Tidskriftsartikel (refereegranskat)abstract
- The European Space Agency's Planck satellite, which was dedicated to studying the early Universe and its subsequent evolution, was launched on 14 May 2009. It scanned the microwave and submillimetre sky continuously between 12 August 2009 and 23 October 2013, producing deep, high-resolution, all-sky maps in nine frequency bands from 30 to 857 GHz. This paper presents the cosmological legacy of Planck, which currently provides our strongest constraints on the parameters of the standard cosmological model and some of the tightest limits available on deviations from that model. The 6-parameter Lambda CDM model continues to provide an excellent fit to the cosmic microwave background data at high and low redshift, describing the cosmological information in over a billion map pixels with just six parameters. With 18 peaks in the temperature and polarization angular power spectra constrained well, Planck measures five of the six parameters to better than 1% (simultaneously), with the best-determined parameter (theta (*)) now known to 0.03%. We describe the multi-component sky as seen by Planck, the success of the Lambda CDM model, and the connection to lower-redshift probes of structure formation. We also give a comprehensive summary of the major changes introduced in this 2018 release. The Planck data, alone and in combination with other probes, provide stringent constraints on our models of the early Universe and the large-scale structure within which all astrophysical objects form and evolve. We discuss some lessons learned from the Planck mission, and highlight areas ripe for further experimental advances.
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