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- Duran-Ferrer, Marti, et al.
(author)
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The proliferative history shapes the DNA methylome of B-cell tumors and predicts clinical outcome
- 2020
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In: NATURE CANCER. - : Springer Nature. - 2662-1347. ; 1:11, s. 1066-1081
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Journal article (peer-reviewed)abstract
- We report a systematic analysis of the DNA methylation variability in 1,595 samples of normal cell subpopulations and 14 tumor subtypes spanning the entire human B-cell lineage. Differential methylation among tumor entities relates to differences in cellular origin and to de novo epigenetic alterations, which allowed us to build an accurate machine learning-based diagnostic algorithm. We identify extensive individual-specific methylation variability in silenced chromatin associated with the proliferative history of normal and neoplastic B cells. Mitotic activity generally leaves both hyper- and hypomethylation imprints, but some B-cell neoplasms preferentially gain or lose DNA methylation. We construct a DNA-methylation-based mitotic clock, called epiCMIT, whose lapse magnitude represents a strong independent prognostic variable in B-cell tumors and is associated with particular driver genetic alterations. Our findings reveal DNA methylation as a holistic tracer of B-cell tumor developmental history, with implications in differential diagnosis and the prediction of clinical outcome. Martin-Subero and colleagues analyze DNA methylation patterns in B-cell tumors and their normal cells of origin, and develop epiCMIT, a methylation-based mitotic clock with prognostic relevance.
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- Lu, Ping, et al.
(author)
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A 5.4GHz wide tuning range CMOS PLL using an auto-calibration multiple-pass ring oscillator
- 2009
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In: [Host publication title missing]. - 9781424449408 ; , s. 39-42
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Conference paper (peer-reviewed)abstract
- A 5.4GHz multiple-pass ring voltage controlled oscillator (VCO) based phase-locked loop (PLL) is described. For the sake of active devices’ sensitivity to process and temperature regarding ring oscillators, an effective automatic frequency calibration scheme is proposed. A new process-independent differential to single (DTOS) is used to adjust control voltage range and loop gain. The chip is implemented in 0.18-um CMOS process and achieves phase noise of -100dBc/Hz@1MHz and a 40% tuning range.
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- Zhang, Hanzhi, et al.
(author)
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Expansion of dust provenance and aridification of Asia since ~7.2 Ma revealed by detrital zircon U-Pb dating
- 2018
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In: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 45:24, s. 13,437-13,448
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Journal article (peer-reviewed)abstract
- The relative importance of global cooling and Tibetan Plateau uplift in driving the aridification of Asia during the late Cenozoic is debated, largely due to the lack of appropriate proxy indicators. Here we address this problem by investigating changes in the source of Chinese loess and Red Clay, which is directly controlled by changes in the extent and distribution of the arid zone of Asia and the intensity of the East Asian winter monsoon, using zircon U‐Pb dating of 27 levels in a near‐continuous eolian sedimentary sequence in southern Chinese Loess Plateau. The results show that source regions expanded stepwise at ~7.2, ~2.6, 1.2–0.9 Ma, and at the Last Glacial Maximum. These changes were synchronous with global cooling and ice cover expansion in the Northern Hemisphere, suggesting that the drivers of aridification of the Asian interior were intimately related to global cooling in the late Cenozoic.Plain Language SummaryThe arid and semiarid regions of Central Asia are one of the most important dust sources on Earth. Dust emitted from these regions is deposited in the Chinese Loess Plateau, the North Pacific Ocean, and even in Greenland, with broad environmental impacts. Although there is evidence that the drying of the Asian interior occurred gradually over several tens of million years, the driving factor remains unclear. Here we investigate the evolution of the sediment sources of the Chinese Loess Plateau and find that the changes in the source regions of wind‐blown sediment were synchronous with global cooling since ~7.2 Ma. This indicates that the long‐term aridification of the Asian interior was most likely driven by global cooling.
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