| 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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| 2. |
- Yin, X., et al.
(författare)
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Vertical Sandwich Gate-All-Around Field-Effect Transistors with Self-Aligned High-k Metal Gates and Small Effective-Gate-Length Variation
- 2020
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Ingår i: IEEE Electron Device Letters. - : Institute of Electrical and Electronics Engineers Inc.. - 0741-3106 .- 1558-0563. ; 41:1, s. 8-11
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Tidskriftsartikel (refereegranskat)abstract
- A new type of vertical nanowire (NW)/nanosheet (NS) field-effect transistors (FETs), termed vertical sandwich gate-all-around (GAA) FETs (VSAFETs), is presented in this work. Moreover, an integration flow that is compatible with processes used in the mainstream industry is proposed for the VSAFETs. Si/SiGe epitaxy, isotropic quasi-atomic-layer etching (qALE), and gate replacement were used to fabricate pVSAFETs for the first time. Vertical GAA FETs with self-aligned high-k metal gates and a small effective-gate-length variation were obtained. Isotropic qALE, including Si-selective etching of SiGe, was developed to control the diameter/thickness of the NW/NS channels. NWs with a diameter of 10 nm and NSs with a thickness of 20 nm were successfully fabricated, and good device characteristics were obtained. Finally, the device performance was investigated and is discussed in this work. © 2019 IEEE.
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| 3. |
- Kristan, M., et al.
(författare)
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The Eighth Visual Object Tracking VOT2020 Challenge Results
- 2020
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Ingår i: Computer Vision. - Cham : Springer International Publishing. - 9783030682378 ; , s. 547-601
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Konferensbidrag (refereegranskat)abstract
- The Visual Object Tracking challenge VOT2020 is the eighth annual tracker benchmarking activity organized by the VOT initiative. Results of 58 trackers are presented; many are state-of-the-art trackers published at major computer vision conferences or in journals in the recent years. The VOT2020 challenge was composed of five sub-challenges focusing on different tracking domains: (i) VOT-ST2020 challenge focused on short-term tracking in RGB, (ii) VOT-RT2020 challenge focused on “real-time” short-term tracking in RGB, (iii) VOT-LT2020 focused on long-term tracking namely coping with target disappearance and reappearance, (iv) VOT-RGBT2020 challenge focused on short-term tracking in RGB and thermal imagery and (v) VOT-RGBD2020 challenge focused on long-term tracking in RGB and depth imagery. Only the VOT-ST2020 datasets were refreshed. A significant novelty is introduction of a new VOT short-term tracking evaluation methodology, and introduction of segmentation ground truth in the VOT-ST2020 challenge – bounding boxes will no longer be used in the VOT-ST challenges. A new VOT Python toolkit that implements all these novelites was introduced. Performance of the tested trackers typically by far exceeds standard baselines. The source code for most of the trackers is publicly available from the VOT page. The dataset, the evaluation kit and the results are publicly available at the challenge website (http://votchallenge.net ).
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| 4. |
- Wang, H. Y., et al.
(författare)
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Cellular Analysis and Comparative Transcriptomics Reveal the Tolerance Mechanisms of Candida tropicalis Toward Phenol
- 2020
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Ingår i: Frontiers in Microbiology. - : Frontiers Media SA. - 1664-302X. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Phenol is a ubiquitous pollutant and can contaminate natural water resources. Hence, the removal of phenol from wastewater is of significant importance. A series of biological methods were used to remove phenol based on the natural ability of microorganisms to degrade phenol, but the tolerance mechanism of phenol-degraded strains to phenol are not very clear. Morphological observation on Candida tropicalis showed that phenol caused the reactive oxygen species (ROS) accumulation, damaging the mitochondrial and the endoplasmic reticulum. On the basis of transcriptome data and cell wall susceptibility analysis, it was found that C. tropicalis prevented phenol-caused cell damage through improvement of cell wall resistance, maintenance of high-fidelity DNA replication, intracellular protein homeostasis, organelle integrity, and kept the intracellular phenol concentration at a low level through cell-wall remodeling and removal of excess phenol via MDR/MXR transporters. The knowledge obtained will promote the genetic modification of yeast strains in general to tolerate the high concentrations of phenol and improve their efficiency of phenol degradation.
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| 5. |
- Zhou, J. M., et al.
(författare)
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Digoxin is associated with worse outcomes in patients with heart failure with reduced ejection fraction
- 2020
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Ingår i: Esc Heart Failure. - : Wiley. - 2055-5822. ; 7:1, s. 139-147
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Tidskriftsartikel (refereegranskat)abstract
- Aims The aim of this study was to investigate the impact of digoxin use on the outcomes of patients with heart failure with reduced ejection fraction (HFrEF) and its possible interaction with atrial fibrillation or use of currently guideline-recommended treatments in the real world in China. Methods and results Patients hospitalized with HFrEF from 45 hospitals participating in the China National Heart Failure Registration Study (CN-HF) were enrolled to assess the all-cause mortality, HF mortality, all-cause re-hospitalization, and HF re-hospitalization associated with digoxin use. Eight hundred eighty-two eligible HFrEF patients in the CN-HF registry were included: 372 patients with digoxin and 510 patients without digoxin. Among them, 794 (90.0%) patients were followed up for the endpoint events, with a median follow-up of 28.6 months. Kaplan-Meier survival analysis showed that the all-cause mortality (P < 0.001) and all-cause re-hospitalization (P = 0.020) were significantly higher in digoxin group than non-digoxin group, while HF mortality (P = 0.232) and HF re-hospitalization (P = 0.098) were similar between the two groups. The adjusted Cox proportional-hazards regression analysis demonstrated that digoxin use remained as an independent risk factor for increased all-cause mortality [hazard ratio (HR) 1.76; 95% confidence interval (CI) 1.27-2.44; P = 0.001] and all-cause re-hospitalization (HR 1.27; 95% CI 1.03-1.57; P = 0.029) in HFrEF patients and the predictive value of digoxin for all-cause mortality irrespective of rhythm or in combination with other guideline-recommended therapies. Conclusions Digoxin use is independently associated with increased risk of all-cause mortality and all-cause re-hospitalization in HFrEF patients.
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| 6. |
- Poley, L., et al.
(författare)
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The ABC130 barrel module prototyping programme for the ATLAS strip tracker
- 2020
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Ingår i: Journal of Instrumentation. - : IOP PUBLISHING LTD. - 1748-0221 .- 1748-0221. ; 15:9
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Tidskriftsartikel (refereegranskat)abstract
- For the Phase-II Upgrade of the ATLAS Detector [1], its Inner Detector, consisting of silicon pixel, silicon strip and transition radiation sub-detectors, will be replaced with an all new 100% silicon tracker, composed of a pixel tracker at inner radii and a strip tracker at outer radii. The future ATLAS strip tracker will include 11,000 silicon sensor modules in the central region (barrel) and 7,000 modules in the forward region (end-caps), which are foreseen to be constructed over a period of 3.5 years. The construction of each module consists of a series of assembly and quality control steps, which were engineered to be identical for all production sites. In order to develop the tooling and procedures for assembly and testing of these modules, two series of major prototyping programs were conducted: an early program using readout chips designed using a 250 nm fabrication process (ABCN-250) [2, 3] and a subsequent program using a follow-up chip set made using 130 nm processing (ABC130 and HCC130 chips). This second generation of readout chips was used for an extensive prototyping program that produced around 100 barrel-type modules and contributed significantly to the development of the final module layout. This paper gives an overview of the components used in ABC130 barrel modules, their assembly procedure and findings resulting from their tests.
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| 7. |
- Wang, Y., et al.
(författare)
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Erythropoietin prevents necrotizing enterocolitis in very preterm infants: a randomized controlled trial
- 2020
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Ingår i: Journal of Translational Medicine. - : Springer Science and Business Media LLC. - 1479-5876. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Necrotizing enterocolitis (NEC) is one of the most severe complications in very preterm infants, but there are currently no accepted methods to prevent NEC. Studies have shown that erythropoietin (EPO) has the potential to prevent NEC or improve outcomes of preterm NEC. This study aimed to determine whether recombinant human EPO (rhEPO) could protect against NEC in very preterm infants. Methods: The study was a prospective randomized clinical trial performed among four NICU centers. A total of 1327 preterm infants with gestational age <= 32 weeks were admitted to the centers, and 42 infants were excluded leaving 1285 eligible infants to be randomized to the rhEPO or control group. Infants in the rhEPO group were given 500 IU/kg rhEPO intravenously every other day for 2 weeks, while the control group was given the same volume of saline. The primary outcome was the incidence of NEC in very preterm infants at 36 weeks of corrected gestational age. Results: A total of 1285 infants were analyzed at 36 weeks of corrected age for the incidence of NEC. rhEPO treatment significantly decreased the incidence of NEC (stage I, II and III) (12.0% vs. 17.1%, p = 0.010), especially confirmed NEC (stage II and III) (3.0% vs. 5.4%, p = 0.027). Meanwhile, rhEPO treatment significantly reduced the number of red blood cells transfusion in the confirmed NEC cases (1.2 +/- 0.4 vs. 2.7 +/- 1.0, p = 0.004). Subgroup analyses showed that rhEPO treatment significantly decreased the incidence of confirmed NEC at gestational age < 28 weeks (p = 0.019), and the incidence of all stages NEC in preterm infants with hemoglobin < 90 g/l (p = 0.000) and 5 min Apgar score > 5 (p = 0.028). Conclusion: Repeated low-dose rhEPO treatment is beneficial against NEC in very preterm infants.
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| 8. |
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| 9. |
- Cheng, X-P, et al.
(författare)
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Compact Bright Radio-loud AGNs. III. A Large VLBA Survey at 43 GHz
- 2020
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Ingår i: Astrophysical Journal, Supplement Series. - : American Astronomical Society. - 1538-4365 .- 0067-0049. ; 247:2
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Tidskriftsartikel (refereegranskat)abstract
- We present the results from the 43 GHz Very Long Baseline Array (VLBA) observations of 124 compact radio-loud active galactic nuclei (AGNs) that were conducted between 2014 November and 2016 May. The typical dimensions of the restoring beam in each image are about 0.5 mas x 0.2 mas. The highest resolution of 0.2 mas corresponds to a physical size of 0.02 pc for the lowest redshift source in the sample. The 43 GHz very long baseline interferometry (VLBI) images of 97 AGNs are presented for the first time. We study the source compactness on milliarcsecond and submilliarcsecond scales, and suggest that 95 sources in our sample are suitable for future space VLBI observations. By analyzing our data supplemented with other VLBA AGN surveys from the literature, we find that the core brightness temperature increases with increasing frequency below a break frequency similar to 7 GHz, and decreases between similar to 7 and 240 GHz but increases again above 240 GHz in the rest frame of the sources. This indicates that the synchrotron opacity changes from optically thick to thin. We also find a strong statistical correlation between radio and gamma-ray flux densities. Our correlation is tighter than those in the literature derived from lower-frequency VLBI data, suggesting that the gamma-ray emission is produced more cospatially with the 43 GHz VLBA core emission. This correlation can also be extrapolated to the unbeamed AGN population, implying that a universal gamma-ray production mechanism might be at work for all types of AGNs.
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| 10. |
- 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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