MicroRNAs have been shown to play an important role in normal hematopoisis and leukemogenesis. Here, we report function and mechanisms of miR-181 family in myeloid differentiation and acute myeloid ...leukemia (AML). The aberrant overexpression of all the miR-181 family members (miR-181a/b/c/d) was detected in French-American-British M1, M2 and M3 subtypes of adult AML patients. By conducting gain- and loss-of-function experiments, we demonstrated that miR-181a inhibits granulocytic and macrophage-like differentiation of HL-60 cells and CD34+ hematopoietic stem/progenitor cells (HSPCs) by directly targeting and downregulating the expression of PRKCD (which then affected the PRKCD-P38-C/EBPα pathway), CTDSPL (which then affected the phosphorylation of retinoblastoma protein) and CAMKK1. The three genes were also demonstrated to be the targets of miR-181b, miR-181c and miR-181d, respectively. Significantly decreases in the expression levels of the target proteins were detected in AML patients. Inhibition of the expression of miR-181 family members owing to Lenti-miRZip-181a infection in bone marrow blasts of AML patients increased target protein expression levels and partially reversed myeloid differentiation blockage. In the mice implanted with AML CD34+ HSPCs, expression inhibition of the miR-181 family by Lenti-miRZip-181a injection improved myeloid differentiation, inhibited engraftment and infiltration of the leukemic CD34+ cells into the bone marrow and spleen, and released leukemic symptoms. In conclusion, our findings revealed new mechanism of miR-181 family in normal hematopoiesis and AML development, and suggested that expression inhibition of the miR-181 family could provide a new strategy for AML therapy.
Large peridotite massifs are scattered along the 1500km length of the Yarlung-Zangbo Suture Zone (southern Tibet, China), the major suture between Asia and Greater India. Diamonds occur in the ...peridotites and chromitites of several massifs, together with an extensive suite of trace phases that indicate extremely low fO sub(2) (SiC, nitrides, carbides, native elements) and/or ultrahigh pressures (UHP) (diamond, TiO sub(2) II, coesite, possible stishovite). New physical and isotopic (C, N) studies of the diamonds indicate that they are natural, crystallized in a disequilibrium, high-T environment, and spent only a short time at mantle temperatures before exhumation and cooling. These constraints are difficult to reconcile with previous models for the history of the diamond-bearing rocks. Possible evidence for metamorphism in or near the upper part of the Transition Zone includes the following: (1) chromite (in disseminated, nodular and massive chromitites) containing exsolved pyroxenes and coesite, suggesting inversion from a high-P polymorph of chromite; (2) microstructural studies suggesting that the chromitites recrystallized from fine-grained, highly deformed mixtures of wadsleyite and an octahedral polymorph of chromite; (3) a new cubic Mg-silicate, with the space group of ringwoodite but an inverse-spinel structure (all Si in octahedral coordination); (4) harzburgites with coarsely vermicular symplectites of opx + Cr-Al spinel plus or minus cpx; reconstructions suggest that these are the breakdown products of majoritic garnets, with estimated minimum pressures to>13GPa. Evidence for a shallow pre-metamorphic origin for the chromitites and peridotites includes the following: (1) trace-element data showing that the chromitites are typical of suprasubduction-zone (SSZ) chromitites formed by magma mixing or mingling, consistent with Hf-isotope data from magmatic (375Ma) zircons in the chromitites; (2) the composition of the new cubic Mg-silicate, which suggests a low-P origin as antigorite, subsequently dehydrated; (3) the peridotites themselves, which carry the trace element signature of metasomatism in an SSZ environment, a signature that must have been imposed before the incorporation of the UHP and low-fO sub(2) phases. A proposed P-T-t path involves the original formation of chromitites in mantle-wedge harzburgites, subduction of these harzburgites at c. 375Ma, residence in the upper Transition Zone for >200 Myr, and rapid exhumation at c. 170-150Ma or 130-120Ma. Os-isotope data suggest that the subducted mantle consisted of previously depleted subcontinental lithosphere, dragged down by a subducting oceanic slab. Thermomechanical modeling shows that roll-back of a (much later) subducting slab would produce a high-velocity channelized upwelling that could exhume the buoyant harzburgites (and their chromitites) from the Transition Zone in<10 Myr. This rapid upwelling, which may explain some characteristics of the diamonds, appears to have brought some massifs to the surface in forearc or back-arc basins, where they provided a basement for oceanic crust. This model can reconcile many apparently contradictory petrological and geological datasets. It also defines an important, previously unrecognized geodynamic process that may have operated along other large suture zones such as the Urals.
The amalgamation of South (SCB) and North China Blocks (NCB) along the Qinling‐Dabie orogenic belt involved several stages of high pressure (HP)‐ultra high pressure (UHP) metamorphism. The new ...discovery of UHP metamorphic rocks in the North Qinling (NQ) terrane can provide valuable information on this process. However, no precise age for the UHP metamorphism in the NQ terrane has been documented yet, and thus hinders deciphering of the evolution of the whole Qinling‐Dabie‐Sulu orogenic belt. This article reports an integrated study of U–Pb age, trace element, mineral inclusion and Hf isotope composition of zircon from an eclogite, a quartz vein and a schist in the NQ terrane. The zircon cores in the eclogite are characterized by oscillatory zoning or weak zoning, high Th/U and 176Lu/177Hf ratios, pronounced Eu anomalies and steep heavy rare earth element (HREE) patterns. The zircon cores yield an age of 796 ± 13 Ma, which is taken as the protolith formation age of the eclogite, and implies that the NQ terrane may belong to the SCB before it collided with the NCB. The ɛHf(t) values vary from −11.3 to 3.2 and corresponding two‐stage Hf model ages are 2402 to 1495 Ma, suggesting the protolith was derived from an enriched mantle. In contrast, the metamorphic zircon rims show no zoning or weak zoning, very low Th/U and 176Lu/177Hf ratios, insignificant Eu anomalies and flat HREE patterns. They contain inclusions of garnet, omphacite and phengite, suggesting that the metamorphic zircon formed under eclogite facies metamorphic conditions, and their weighted mean 206Pb/238U age of 485.9 ± 3.8 Ma was interpreted to date the timing of the eclogite facies metamorphism. Zircon in the quartz vein is characterized by perfect euhedral habit, some oscillatory zoning, low Th/U ratios and variable HREE contents. It yields a weighted mean U–Pb age of 480.5 ± 2.5 Ma, which registers the age of fluid activity during exhumation. Zircon in the schist is mostly detrital and U–Pb age peaks at c. 1950 to 1850, 1800 to 1600, 1560 to 1460 and 1400 to 1260 Ma with an oldest grain of 2517 Ma, also suggesting that the NQ terrane may have an affinity to the SCB. Accordingly, the amalgamation between the SCB and the NCB is a multistage process that spans c. 300 Myr, which includes: the formation of the Erlangping intra‐oceanic arc zone onto the NCB before c. 490 Ma, the c. 485 Ma crustal subduction and UHP metamorphism of the NQ terrane, the c. 430 Ma arc‐continent collision and granulite facies metamorphism, the 420 to 400 Ma extension and rifting in relation to the opening of the Palaeo‐Tethyan ocean, the c. 310 Ma HP eclogite facies metamorphism of oceanic crust and associated continental basement, and the final 250 to 220 Ma continental subduction and HP–UHP metamorphism.
High-β_{θe} (a ratio of the electron thermal pressure to the poloidal magnetic pressure) steady-state long-pulse plasmas with steep central electron temperature gradient are achieved in the ...Experimental Advanced Superconducting Tokamak. An intrinsic current is observed to be modulated by turbulence driven by the electron temperature gradient. This turbulent current is generated in the countercurrent direction and can reach a maximum ratio of 25% of the bootstrap current. Gyrokinetic simulations and experimental observations indicate that the turbulence is the electron temperature gradient mode (ETG). The dominant mechanism for the turbulent current generation is due to the divergence of ETG-driven residual flux of current. Good agreement has been found between experiments and theory for the critical value of the electron temperature gradient triggering ETG and for the level of the turbulent current. The maximum values of turbulent current and electron temperature gradient lead to the destabilization of an m/n=1/1 kink mode, which by counteraction reduces the turbulence level (m and n are the poloidal and toroidal mode number, respectively). These observations suggest that the self-regulation system including turbulence, turbulent current, and kink mode is a contributing mechanism for sustaining the steady-state long-pulse high-β_{θe} regime.
We report a measurement of electron antineutrino oscillation from the Daya Bay Reactor Neutrino Experiment with nearly 4 million reactor νover ¯_{e} inverse β decay candidates observed over 1958 days ...of data collection. The installation of a flash analog-to-digital converter readout system and a special calibration campaign using different source enclosures reduce uncertainties in the absolute energy calibration to less than 0.5% for visible energies larger than 2 MeV. The uncertainty in the cosmogenic ^{9}Li and ^{8}He background is reduced from 45% to 30% in the near detectors. A detailed investigation of the spent nuclear fuel history improves its uncertainty from 100% to 30%. Analysis of the relative νover ¯_{e} rates and energy spectra among detectors yields sin^{2}2θ_{13}=0.0856±0.0029 and Δm_{32}^{2}=(2.471_{-0.070}^{+0.068})×10^{-3} eV^{2} assuming the normal hierarchy, and Δm_{32}^{2}=-(2.575_{-0.070}^{+0.068})×10^{-3} eV^{2} assuming the inverted hierarchy.
Abstract We present the first catalog of very-high-energy and ultra-high-energy gamma-ray sources detected by the Large High Altitude Air Shower Observatory. The catalog was compiled using 508 days ...of data collected by the Water Cherenkov Detector Array from 2021 March to 2022 September and 933 days of data recorded by the Kilometer Squared Array from 2020 January to 2022 September. This catalog represents the main result from the most sensitive large coverage gamma-ray survey of the sky above 1 TeV, covering decl. from −20° to 80°. In total, the catalog contains 90 sources with an extended size smaller than 2° and a significance of detection at >5 σ . Based on our source association criteria, 32 new TeV sources are proposed in this study. Among the 90 sources, 43 sources are detected with ultra-high energy ( E > 100 TeV) emission at >4 σ significance level. We provide the position, extension, and spectral characteristics of all the sources in this catalog.
ABSTRACT
High time resolution and accuracy are of critical importance in the studies of timing analysis and time delay localization of gamma-ray bursts (GRBs), soft gamma-ray repeaters (SGRs) and ...pulsars. The Gravitational wave high-energy Electromagnetic Counterpart All-sky Monitor (GECAM) consisting of two micro-satellites, GECAM-A and GECAM-B, launched on 2020 December 10, is aimed at monitoring and locating X-ray and GRBs all over the sky. To achieve its scientific goals, GECAM is designed to have the highest time resolution (0.1 $\mu {\rm s}$) among all GRB detectors ever flown. Here, we make a comprehensive time calibration campaign including both on-ground and on-orbit tests to derive not only the relative time accuracy of GECAM satellites and detectors, but also the absolute time accuracy of GECAM-B. Using the on-ground calibration with a $\rm ^{22}Na$ radioactive source, we find that the relative time accuracy between GECAM-A and GECAM-B is about 0.15 $\mu {\rm s}$ (1σ). To measure the relative time accuracy between all detectors of a single GECAM satellite, cosmic-ray events detected on orbit are utilized since they could produce many secondary particles simultaneously record by multiple detectors. We find that the relative time accuracy among all detectors onboard GECAM-B is about 0.12 $\mu {\rm s}$ (1σ). Finally, we use the novel Li-CCF method to perform the absolute time calibration with Crab pulsar and SGR J1935+2154, both of which were jointly observed by GECAM-B and Fermi/GBM, and obtain that the time difference between GECAM-B and Fermi/GBM is 3.06 ± 6.04 $\mu {\rm s}$ (1σ).
The Daya Bay experiment has observed correlations between reactor core fuel evolution and changes in the reactor antineutrino flux and energy spectrum. Four antineutrino detectors in two experimental ...halls were used to identify 2.2 million inverse beta decays (IBDs) over 1230 days spanning multiple fuel cycles for each of six 2.9 GW_{th} reactor cores at the Daya Bay and Ling Ao nuclear power plants. Using detector data spanning effective ^{239}Pu fission fractions F_{239} from 0.25 to 0.35, Daya Bay measures an average IBD yield σover ¯_{f} of (5.90±0.13)×10^{-43} cm^{2}/fission and a fuel-dependent variation in the IBD yield, dσ_{f}/dF_{239}, of (-1.86±0.18)×10^{-43} cm^{2}/fission. This observation rejects the hypothesis of a constant antineutrino flux as a function of the ^{239}Pu fission fraction at 10 standard deviations. The variation in IBD yield is found to be energy dependent, rejecting the hypothesis of a constant antineutrino energy spectrum at 5.1 standard deviations. While measurements of the evolution in the IBD spectrum show general agreement with predictions from recent reactor models, the measured evolution in total IBD yield disagrees with recent predictions at 3.1σ. This discrepancy indicates that an overall deficit in the measured flux with respect to predictions does not result from equal fractional deficits from the primary fission isotopes ^{235}U, ^{239}Pu, ^{238}U, and ^{241}Pu. Based on measured IBD yield variations, yields of (6.17±0.17) and (4.27±0.26)×10^{-43} cm^{2}/fission have been determined for the two dominant fission parent isotopes ^{235}U and ^{239}Pu. A 7.8% discrepancy between the observed and predicted ^{235}U yields suggests that this isotope may be the primary contributor to the reactor antineutrino anomaly.
Abstract
We report the discovery of an ultrahigh-energy (UHE) gamma-ray source, LHAASO J2108+5157, by analyzing the LHAASO-KM2A data of 308.33 live days. A significant excess of gamma ray–induced ...showers is observed in both energy bands of 25−100 and >100 TeV with 9.5
σ
and 8.5
σ
, respectively. This source is not significantly favored as an extended source with an angular extension smaller than the point-spread function of KM2A. The measured energy spectrum from 20 to 200 TeV can be approximately described by a power-law function with an index of −2.83 ± 0.18
stat
. A harder spectrum is demanded at lower energies considering the flux upper limit set by Fermi-LAT observations. The position of the gamma-ray emission is correlated with a giant molecular cloud, which favors a hadronic origin. No obvious counterparts have been found, and deeper multiwavelength observations will help to cast new light on this intriguing UHE source.
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