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).
Summary Objective This study aimed to investigate the role of the Wnt/β-catenin signaling pathway and E-cadherin/β-catenin complex in intermittent cyclic mechanical tension (ICMT)-induced endplate ...cartilage degeneration. Design β-Catenin expression was measured in disc samples obtained from patients with disc degeneration and those with cervical vertebrae fracture or dislocation. Histological staining was performed to examine the disc tissue morphology and extracellular matrix after application of ICMT in vitro and in vivo. Multiple strategies were employed to examine activation of Wnt/β-catenin signaling after ICMT application in vivo and in vitro . Co-immunoprecipitation was performed to examine the interaction between E-cadherin and β-catenin. Pathway-specific inhibitors and an E-cadherin expression plasmid were used to regulate Wnt/β-catenin signaling and E-cadherin expression. Results β-Catenin protein expression was elevated significantly, whereas cartilaginous genes were down-regulated in endplate cartilage samples obtained from patients with disc degeneration. ICMT loading led to Wnt/β-catenin signaling activation and the loss of the chondrogenic phenotype of endplate chondrocytes in both an in vivo rabbit model and in vitro endplate chondrocyte culture system. Inhibition of Wnt/β-catenin signaling suppressed the decrease in ICMT-induced cartilaginous gene expression. Furthermore, E-cadherin expression was inhibited by ICMT stimulation, resulting in a decrease in the interaction between E-cadherin and β-catenin proteins. Over-expression of E-cadherin rescued the cartilaginous gene expression by enhancing the interaction between E-cadherin and β-catenin proteins. Conclusions ICMT promotes endplate cartilage degeneration via activation of Wnt/β-catenin signaling and suppression of physical protein–protein interactions between E-cadherin and β-catenin.
Cancer cells are known to execute reprogramed metabolism of glucose, amino acids and lipids. Here, we report a significant role of cholesterol metabolism in cancer metastasis. By using label-free ...Raman spectromicroscopy, we found an aberrant accumulation of cholesteryl ester in human pancreatic cancer specimens and cell lines, mediated by acyl-CoA cholesterol acyltransferase-1 (ACAT-1) enzyme. Expression of ACAT-1 showed a correlation with poor patient survival. Abrogation of cholesterol esterification, either by an ACAT-1 inhibitor or by shRNA knockdown, significantly suppressed tumor growth and metastasis in an orthotopic mouse model of pancreatic cancer. Mechanically, ACAT-1 inhibition increased intracellular free cholesterol level, which was associated with elevated endoplasmic reticulum stress and caused apoptosis. Collectively, our results demonstrate a new strategy for treating metastatic pancreatic cancer by inhibiting cholesterol esterification.
Abstract
The interaction between the solar wind and the magnetosphere is one of the most important research subjects in the fields of astrophysics and space physics. For more than half a century, ...based on the pressure balance assumption between the solar wind and the magnetosphere and considering other important factors, such as the interplanetary magnetic field and magnetic reconnection process, the dynamic processes at the magnetopause have been extensively analyzed. However, the responses of magnetopause to the solar wind dynamic pressure variations are still complicated to understand. Here, we show that the interaction between the solar wind and the magnetosphere can be regarded as a quasi-elastodynamic process. The driving frequency of the solar wind is determined as a crucial reason for the phase difference between solar wind dynamic pressure variations and magnetopause standoff distance. The low-pass filter effect and oscillation properties of the magnetopause can also be well explained by the forced damped vibrations. Moreover, the quasi-elastodynamic processes predict deformations at the magnetopause, which resemble the magnetopause surface wave. Finally, a three-dimensional time-dependent magnetopause model is constructed and verified by observation. Based on 12,242 magnetopause crossing events, it is found that the new model reveals ∼9.7% better prediction accuracy than the widely used time-independent model. These results can also shed light on our understanding of the solar-wind–magnetopause interaction for other planets.
The independent control of two magnetic electrodes and spin-coherent transport in magnetic tunnel junctions are strictly required for tunneling magnetoresistance, while junctions with only one ...ferromagnetic electrode exhibit tunneling anisotropic magnetoresistance dependent on the anisotropic density of states with no room temperature performance so far. Here, we report an alternative approach to obtaining tunneling anisotropic magnetoresistance in α'-FeRh-based junctions driven by the magnetic phase transition of α'-FeRh and resultantly large variation of the density of states in the vicinity of MgO tunneling barrier, referred to as phase transition tunneling anisotropic magnetoresistance. The junctions with only one α'-FeRh magnetic electrode show a magnetoresistance ratio up to 20% at room temperature. Both the polarity and magnitude of the phase transition tunneling anisotropic magnetoresistance can be modulated by interfacial engineering at the α'-FeRh/MgO interface. Besides the fundamental significance, our finding might add a different dimension to magnetic random access memory and antiferromagnet spintronics.Tunneling anisotropic magnetoresistance is promising for next generation memory devices but limited by the low efficiency and functioning temperature. Here the authors achieved 20% tunneling anisotropic magnetoresistance at room temperature in magnetic tunnel junctions with one α'-FeRh magnetic electrode.
ABSTRACT
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.
Aim
Gastroparesis is a common non‐motor system symptom of Parkinson's disease (PD). However, the mechanism responsible for the gastric motor abnormality is not clear. We previously reported on the ...impaired gastric motility in 6‐hydroxydopamine (6‐OHDA) rats, which were treated with a bilateral microinjection of 6‐OHDA in the substantia nigra (SN). We hypothesize that the enhanced dopamine system and reduced acetylcholine (Ach) in gastric tissues might contribute to the delayed gastric emptying observed in PD.
Methods
A strain gauge force transducer, digital X‐ray imaging system, Western blot, immunofluorescence and Radio Immunoassay were used in this study.
Results
Dopaminergic neurones in the SN were greatly reduced following the bilateral microinjection of 6‐OHDA. 6‐OHDA rats exhibited impaired gastric motility and delayed gastric emptying, accompanied by increased dopamine content and the overexpression of D2 receptors in the stomach. The administration of the D2 receptor antagonist domperidone relieved gastric dysmotility in 6‐OHDA rats, but the D1 receptor antagonist SCH23390 failed to do so. Subdiaphragmatic vagotomy prevented the increase in the gastric dopamine content and D2 receptor expression and improved gastric dysmotility in 6‐OHDA rats.
Conclusion
Dopaminergic deficiency in the SN results in impaired gastric motility, possibly as a result of the enhanced activity of dopamine system and reduced Ach in gastric tissue. The vagus nerve plays an important role in peripheral gastric motility disorder.
The limitations of cancer cell lines have led to the development of direct patient-derived xenograft models. However, the interplay between the implanted human cancer cells and recruited mouse ...stromal and immune cells alters the tumor microenvironment and limits the value of these models. To overcome these constraints, we have developed a technique to expand human hematopoietic stem and progenitor cells (HSPCs) and use them to reconstitute the radiation-depleted bone marrow of a NOD/SCID/IL2rg(-/-) (NSG) mouse on which a patient's tumor is then transplanted (XactMice). The human HSPCs produce immune cells that home into the tumor and help replicate its natural microenvironment. Despite previous passage on nude mice, the expression of epithelial, stromal and immune genes in XactMice tumors aligns more closely to that of the patient tumor than to those grown in non-humanized mice-an effect partially facilitated by human cytokines expressed by both the HSPC progeny and the tumor cells. The human immune and stromal cells produced in the XactMice can help recapitulate the microenvironment of an implanted xenograft, reverse the initial genetic drift seen after passage on non-humanized mice and provide a more accurate tumor model to guide patient treatment.
We performed the broadband (1-100 keV) spectral analysis of the first Galactic Be ultraluminous X-ray pulsar (BeULX) Swift J0243.6+6124 observed by Insight-HXMT during the 2017−2018 outburst. The ...results show spectral transitions at two typical luminosities, roughly consistently with those reported previously via pure timing analysis. We find that the spectrum evolves and becomes softer and has higher cutoff energies until the luminosity reaches L1 (∼1.5 × 1038 erg s−1). Afterwards the spectrum becomes harder with lower cutoff energies until the luminosity increases to L2 (∼4.4 × 1038 erg s−1), around which the second spectral transition occurs. Beyond L2, the spectrum softens again and has larger cutoff energies. Similar behaviors were observed previously in other high-mass X-ray binary systems (HMXBs), especially for the second transition at higher luminosities, which is believed to have a correlation with the magnetic field of the harbored neutron star. Accordingly, we speculate that Swift J0243.6+6124 owns a neutron star with magnetic field strength >1013 G. The spectral transition at around L1 of Swift J0243.6+6124 is first observed thoroughly for any HMXB outburst characterized by strong evolution of the thermal component: the temperature of the blackbody drops sharply accompanied by a sudden increase of the blackbody radius. These spectral transitions can in principle be understood in a general scenario of balancing the emission patterns between the pencil and the fan beams at the magnetic pole, for which the extreme brightness of Swift J0243.6+6124 may provide an almost unique lab to probe the details.
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