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- Wang, Shih-Hao, et al.
(författare)
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TAROGE-M : radio antenna array on antarctic high mountain for detecting near-horizontal ultra-high energy air showers
- 2022
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Ingår i: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :11
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Tidskriftsartikel (refereegranskat)abstract
- The TAROGE-M radio observatory is a self-triggered antenna array on top of the similar to 2700m high Mt. Melbourne in Antarctica, designed to detect impulsive geomagnetic emission from extensive air showers induced by ultra-high energy (UHE) particles beyond 1017 eV, including cosmic rays, Earth-skimming tau neutrinos, and particularly, the "ANITA anomalous events" (AAE) from near and below the horizon. The six AAE discovered by the ANITA experiment have signal features similar to tau neutrinos but that hypothesis is in tension either with the interaction length predicted by Standard Model or with the flux limits set by other experiments. Their origin remains uncertain, requiring more experimental inputs for clarification. The detection concept of TAROGE-M takes advantage of a high altitude with synoptic view toward the horizon as an efficient signal collector, and the radio quietness as well as strong and near vertical geomagnetic field in Antarctica, enhancing the relative radio signal strength. This approach has a low energy threshold, high duty cycle, and is easy to extend for quickly enlarging statistics. Here we report experimental results from the first TAROGEM station deployed in January 2020, corresponding to approximately one month of livetime. The station consists of six receiving antennas operating at 180-450 MHz, and can reconstruct source directions of impulsive events with an angular resolution of similar to 0.3 ffi, calibrated in situ with a drone-borne pulser system. To demonstrate TAROGE-M's ability to detect UHE air showers, a search for cosmic ray signals in 25.3-days of data together with the detection simulation were conducted, resulting in seven identified candidates. The detected events have a mean reconstructed energy of 0.95+0.46 -0.31 EeV and zenith angles ranging from 25 ffi to 82 ffi, with both distributions agreeing with the simulations, indicating an energy threshold at about 0.3 EeV. The estimated cosmic ray flux at that energy is 1.2+0.7 -0.9x10(-16) eV(-1) km(-2) yr(-1) sr(-1), also consistent with results of other experiments. The TAROGE-M sensitivity to AAEs is approximated by the tau neutrino exposure with simulations, which suggests comparable sensitivity as ANITA's at around 1 EeV energy with a few station-years of operation. These first results verified the station design and performance in a polar and high-altitude environment, and are promising for further discovery of tau neutrinos and AAEs after an extension in the near future.
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- Lin, Chia-Yeh, et al.
(författare)
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H2B Mono-ubiquitylation Facilitates Fork Stalling and Recovery during Replication Stress by Coordinating Rad53 Activation and Chromatin Assembly
- 2014
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Ingår i: PLOS Genetics. - : Public library science. - 1553-7390 .- 1553-7404. ; 10:10, s. e1004667-
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Tidskriftsartikel (refereegranskat)abstract
- The influence of mono-ubiquitylation of histone H2B (H2Bub) on transcription via nucleosome reassembly has been widely documented. Recently, it has also been shown that H2Bub promotes recovery from replication stress; however, the underling molecular mechanism remains unclear. Here, we show that H2B ubiquitylation coordinates activation of the intra-S replication checkpoint and chromatin re-assembly, in order to limit fork progression and DNA damage in the presence of replication stress. In particular, we show that the absence of H2Bub affects replication dynamics (enhanced fork progression and reduced origin firing), leading to γH2A accumulation and increased hydroxyurea sensitivity. Further genetic analysis indicates a role for H2Bub in transducing Rad53 phosphorylation. Concomitantly, we found that a change in replication dynamics is not due to a change in dNTP level, but is mediated by reduced Rad53 activation and destabilization of the RecQ helicase Sgs1 at the fork. Furthermore, we demonstrate that H2Bub facilitates the dissociation of the histone chaperone Asf1 from Rad53, and nucleosome reassembly behind the fork is compromised in cells lacking H2Bub. Taken together, these results indicate that the regulation of H2B ubiquitylation is a key event in the maintenance of genome stability, through coordination of intra-S checkpoint activation, chromatin assembly and replication fork progression.
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- Xu, An, et al.
(författare)
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Rewired m6A epitranscriptomic networks link mutant p53 to neoplastic transformation
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- N6-methyladenosine (m6A), one of the most prevalent mRNA modifications in eukaryotes, plays a critical role in modulating both biological and pathological processes. However, it is unknown whether mutant p53 neomorphic oncogenic functions exploit dysregulation of m6A epitranscriptomic networks. Here, we investigate Li-Fraumeni syndrome (LFS)-associated neoplastic transformation driven by mutant p53 in iPSC-derived astrocytes, the cell-of-origin of gliomas. We find that mutant p53 but not wild-type (WT) p53 physically interacts with SVIL to recruit the H3K4me3 methyltransferase MLL1 to activate the expression of m6A reader YTHDF2, culminating in an oncogenic phenotype. Aberrant YTHDF2 upregulation markedly hampers expression of multiple m6A-marked tumor-suppressing transcripts, including CDKN2B and SPOCK2, and induces oncogenic reprogramming. Mutant p53 neoplastic behaviors are significantly impaired by genetic depletion of YTHDF2 or by pharmacological inhibition using MLL1 complex inhibitors. Our study reveals how mutant p53 hijacks epigenetic and epitranscriptomic machinery to initiate gliomagenesis and suggests potential treatment strategies for LFS gliomas.
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