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  • 1
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    Redox-active quinones induces genome-wide DNA methylation changes by an iron-mediated and Tet-dependent mechanism (2014)
    Oxford University Press
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    Publication Date: 2014-02-11
    Description: DNA methylation has been proven to be a critical epigenetic mark important for various cellular processes. Here, we report that redox-active quinones, a ubiquitous class of chemicals found in natural products, cancer therapeutics and environment, stimulate the conversion of 5mC to 5hmC in vivo , and increase 5hmC in 5751 genes in cells. 5hmC increase is associated with significantly altered gene expression of 3414 genes. Interestingly, in quinone-treated cells, labile iron-sensitive protein ferritin light chain showed a significant increase at both mRNA and protein levels indicating a role of iron regulation in stimulating Tet-mediated 5mC oxidation. Consistently, the deprivation of cellular labile iron using specific chelator blocked the 5hmC increase, and a delivery of labile iron increased the 5hmC level. Moreover, both Tet1/Tet2 knockout and dimethyloxalylglycine-induced Tet inhibition diminished the 5hmC increase. These results suggest an iron-regulated Tet-dependent DNA demethylation mechanism mediated by redox-active biomolecules.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 2
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    Genome-wide loss of 5-hmC is a novel epigenetic feature of Huntington's disease (2013)
    Oxford University Press
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    Publication Date: 2013-08-23
    Description: 5-Hydroxymethylcytosine (5-hmC) may represent a new epigenetic modification of cytosine. While the dynamics of 5-hmC during neurodevelopment have recently been reported, little is known about its genomic distribution and function(s) in neurodegenerative diseases such as Huntington's disease (HD). We here observed a marked reduction of the 5-hmC signal in YAC128 (yeast artificial chromosome transgene with 128 CAG repeats) HD mouse brain tissues when compared with age-matched wild-type (WT) mice, suggesting a deficiency of 5-hmC reconstruction in HD brains during postnatal development. Genome-wide distribution analysis of 5-hmC further confirmed the diminishment of the 5-hmC signal in striatum and cortex in YAC128 HD mice. General genomic features of 5-hmC are highly conserved, not being affected by either disease or brain regions. Intriguingly, we have identified disease-specific (YAC128 versus WT) differentially hydroxymethylated regions (DhMRs), and found that acquisition of DhmRs in gene body is a positive epigenetic regulator for gene expression. Ingenuity pathway analysis (IPA) of genotype-specific DhMR-annotated genes revealed that alternation of a number of canonical pathways involving neuronal development/differentiation (Wnt/β-catenin/Sox pathway, axonal guidance signaling pathway) and neuronal function/survival (glutamate receptor/calcium/CREB, GABA receptor signaling, dopamine-DARPP32 feedback pathway, etc.) could be important for the onset of HD. Our results indicate that loss of the 5-hmC marker is a novel epigenetic feature in HD, and that this aberrant epigenetic regulation may impair the neurogenesis, neuronal function and survival in HD brain. Our study also opens a new avenue for HD treatment; re-establishing the native 5-hmC landscape may have the potential to slow/halt the progression of HD.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 3
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    Timing analysis of 2S 1417-624 observed with NICER and Insight-HXMT (2019)
    Oxford University Press
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    Publication Date: 2019-10-22
    Description: We present a study of timing properties of the accreting pulsar 2S 1417-624 observed during its 2018 outburst, based on Swift/BAT, Fermi/GBM, Insight-HXMT and NICER observations. We report a dramatic change of the pulse profiles with luminosity. The morphology of the profile in the range 0.2-10.0 keV switches from double to triple peaks at ∼2.5 $ m imes 10^{37}{it D}_{10}^2 erg s^{-1}$ and from triple to quadruple peaks at ∼7 $ m imes 10^{37}{it D}_{10}^2 erg s^{-1}$. The profile at high energies (25-100 keV) shows significant evolutions as well. We explain this phenomenon according to existing theoretical models. We argue that the first change is related to the transition from the sub to the super-critical accretion regime, while the second to the transition of the accretion disc from the gas-dominated to the radiation pressure-dominated state. Considering the spin-up as well due to the accretion torque, this interpretation allows to estimate the magnetic field self-consistently at ∼7 × 1012 G.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press on behalf of The Royal Astronomical Society.
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  • 4
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    Hot disk of the Swift J0243.6+6124 revealed by Insight-HXMT (2019)
    Oxford University Press
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    Publication Date: 2019-10-22
    Description: We report on analysis of observations of the bright transient X-ray pulsar Swift J0243.6+6124 obtained during its 2017-2018 giant outburst with Insight-HXMT, NuSTAR, and Swift observatories. We focus on the discovery of a sharp state transition of the timing and spectral properties of the source at super-Eddington accretion rates, which we associate with the transition of the accretion disk to a radiation pressure dominated (RPD) state, the first ever directly observed for magnetized neutron star. This transition occurs at slightly higher luminosity compared to already reported transition of the source from sub- to super-critical accretion regime associate with onset of an accretion column. We argue that this scenario can only be realized for comparatively weakly magnetized neutron star, not dissimilar to other ultra-luminous X-ray pulsars (ULPs), which accrete at similar rates. Further evidence for this conclusion is provided by the non-detection of the transition to the propeller state in quiescence which strongly implies compact magnetosphere and thus rules out magnetar-like fields.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press on behalf of The Royal Astronomical Society.
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  • 5
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    Physical origin of the non-physical spin evolution of MAXI J1820 + 070 (2021)
    Oxford University Press
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    Publication Date: 2021-04-06
    Description: We report on the Insight-HXMT observations of the new black hole X-ray binary MAXI J1820+070 during its 2018 outburst. Detailed spectral analysis via the continuum fitting method shows an evolution of the inferred spin during its high soft sate. Moreover, the hardness ratio, the non-thermal luminosity and the reflection fraction also undergo an evolution, exactly coincident to the period when the inferred spin transition takes place. The unphysical evolution of the spin is attributed to the evolution of the inner disc, which is caused by the collapse of a hot corona due to condensation mechanism or may be related to the deceleration of a jet-like corona. The studies of the inner disc radius and the relation between the disc luminosity and the inner disc radius suggest that, only at a particular epoch, did the inner edge of the disc reach the innermost stable circular orbit and the spin measurement is reliable. We then constrain the spin of MAXI J1820 + 070 to be $a_*=0.2^{+0.2}_{-0.3}$. Such a slowly spinning black hole possessing a strong jet suggests that its jet activity is driven mainly by the accretion disc rather than by the black hole spin.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press on behalf of The Royal Astronomical Society.
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  • 6
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    Search for gamma-ray bursts and gravitational wave electromagnetic counterparts with High Energy X-ray Telescope of Insight-HXMT (2021)
    Oxford University Press
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    Publication Date: 2021-09-25
    Description: The High Energy (HE) X-ray telescope on board the Hard X-ray Modulation Telescope (Insight-HXMT) can serve as a wide field of view (FOV) gamma-ray monitor with high time resolution (μs) and large effective area (up to thousands cm2). We developed a pipeline to search for gamma-ray bursts (GRBs), using the traditional signal-to-noise ratio (SNR) method for blind search and the coherent search method for targeted search. By taking into account the location and spectrum of the burst and the detector response, the targeted coherent search is more powerful to unveil weak and sub-threshold bursts, especially those in temporal coincidence with gravitational wave (GW) events. Based on the original method in literature, we further improved the coherent search to filter out false triggers caused by spikes in light curves, which are commonly seen in gamma-ray instruments (e.g. Fermi/GBM, POLAR). We show that our improved targeted coherent search method could eliminate almost all false triggers caused by spikes. Based on the first two years of Insight-HXMT/HE data, our targeted search recovered 40 GRBs, which were detected by either Swift/BAT or Fermi/GBM but too weak to be found in our blind search. With this coherent search pipeline, the GRB detection sensitivity of Insight-HXMT/HE is increased to about 1.5E-08 erg cm−2 (200 keV–3 MeV). We also used this targeted coherent method to search Insight-HXMT/HE data for electromagnetic counterparts of LIGO-Virgo GW events (including O2 and O3a runs). However, we did not find any significant burst associated with GW events.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press on behalf of The Royal Astronomical Society.
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  • 7
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    The NGC 4013 tale: a pseudo-bulged, late-type spiral shaped by a major merger (2015)
    Oxford University Press
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    Publication Date: 2015-08-08
    Description: Many spiral galaxy haloes show stellar streams with various morphologies when observed with deep images. The origin of these tidal features is discussed, either coming from a satellite infall or caused by residuals of an ancient, gas-rich major merger. By modelling the formation of the peculiar features observed in the NGC 4013 halo, we investigate their origin. By using gadget -2 with implemented gas cooling, star formation, and feedback, we have modelled the overall NGC 4013 galaxy and its associated halo features. A gas-rich major merger occurring 2.7–4.6 Gyr ago succeeds in reproducing the NGC 4013 galaxy properties, including all the faint stellar features, strong gas warp, boxy-shaped halo and vertical 3.6 μm luminosity distribution. High gas fractions in the progenitors are sufficient to reproduce the observed thin and thick discs, with a small bulge fraction, as observed. A major merger is able to reproduce the overall NGC 4013 system, including the warp strength, the red colour and the high stellar mass density of the loop, while a minor merger model cannot. Because the gas-rich model suffices to create a pseudo-bulge with a small fraction of the light, NGC 4013 is perhaps the archetype of a late-type galaxy formed by a relatively recent merger. Then late type, pseudo-bulge spirals are not mandatorily made through secular evolution, and the NGC 4013 properties also illustrate that strong warps in isolated galaxies may well occur at a late phase of a gas-rich major merger.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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  • 8
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    Reciprocity relations for the elastodynamic fields generated by multipole sources in a fluid-solid configuration (2015)
    Oxford University Press
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    Publication Date: 2015-09-13
    Description: Employing dynamic reciprocity can be an effective tool to simplify the calculation of elastic wavefields for borehole problems and to check the results. We analytically obtain the reciprocity relations for the elastodynamic fields generated by multipole sources in a fluid–solid configuration: if the multipole sources are located in the fluid, the particle displacement due to a dipole source is reciprocal to the particle acceleration due to a single force; the fluid pressure due to a dipole source is reciprocal to the particle acceleration due to a monopole source; the particle displacement due to a quadrupole source is reciprocal to the spatial partial derivative of the particle acceleration due to a single force; the fluid pressure due to a quadrupole source is reciprocal to the spatial partial derivative of the particle acceleration due to a monopole source. These relations are tested by numerical experiments for different borehole problems, including acoustic logging, single-well imaging and vertical seismic profiling. A reciprocity test can be used as a quick check of a finite-difference algorithm and the implementation of the sources, although it cannot detect errors due to improper discretization of the interfaces.
    Keywords: Marine Geosciences and Applied Geophysics
    Print ISSN: 0956-540X
    Electronic ISSN: 1365-246X
    Topics: Geosciences
    Published by Oxford University Press on behalf of The Deutsche Geophysikalische Gesellschaft (DGG) and the Royal Astronomical Society (RAS).
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  • 9
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    Deterministic identification of specific individuals from GWAS results (2015)
    Oxford University Press
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    Publication Date: 2015-05-27
    Description: Motivation : Genome-wide association studies (GWASs) are commonly applied on human genomic data to understand the causal gene combinations statistically connected to certain diseases. Patients involved in these GWASs could be re-identified when the studies release statistical information on a large number of single-nucleotide polymorphisms. Subsequent work, however, found that such privacy attacks are theoretically possible but unsuccessful and unconvincing in real settings. Results : We derive the first practical privacy attack that can successfully identify specific individuals from limited published associations from the Wellcome Trust Case Control Consortium (WTCCC) dataset. For GWAS results computed over 25 randomly selected loci, our algorithm always pinpoints at least one patient from the WTCCC dataset. Moreover, the number of re-identified patients grows rapidly with the number of published genotypes. Finally, we discuss prevention methods to disable the attack, thus providing a solution for enhancing patient privacy. Availability and implementation : Proofs of the theorems and additional experimental results are available in the support online documents. The attack algorithm codes are publicly available at https://sites.google.com/site/zhangzhenjie/GWAS_attack.zip . The genomic dataset used in the experiments is available at http://www.wtccc.org.uk/ on request. Contact : winslett@illinois.edu or zhenjie@adsc.com.sg Supplementary information: Supplementary data are available from Bioinformatics online.
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
    Published by Oxford University Press
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  • 10
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    Time analyticity with higher norm estimates for the 2D Navier-Stokes equations (2015)
    Oxford University Press
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    Publication Date: 2015-05-26
    Description: This paper establishes bounds on norms of all orders for solutions on the global attractor of the 2D Navier–Stokes equations, complexified in time. Specifically, for periodic boundary conditions on [0, L ] 2 , and a force g D( A (α–1)/2 ), we show that there is a fixed strip about the real-time axis on which a uniform bound $|A^{\alpha}u| 〈 m_{\alpha}\nu\kappa_{0}^{\alpha}$ holds for each $\alpha \in {\mathbb {N}}$ . Here is viscosity, $\kappa_{0}=2\pi/L$ , and m α is explicitly given in terms of g and α. We show that if any element in A is in $\mathcal{D}(A^{\alpha})$ , then all of A is in $\mathcal{D}(A^{\alpha})$ , and likewise with $\mathcal{D}(A^{\alpha})$ replaced by $C^{\infty}(\Omega)$ . We demonstrate the universality of this ‘all for one, one for all’ law is also shown to hold for the union of a hierarchical set of function classes. Finally, we treat the question of whether the zero solution can be in the global attractor for a non-zero force by showing that if this is so, the force must be in a particular function class.
    Print ISSN: 0272-4960
    Electronic ISSN: 1464-3634
    Topics: Mathematics
    Published by Oxford University Press
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