An epigenetic switch induced by Shh signalling regulates gene activation during development and medulloblastoma growth

The Sonic hedgehog (Shh) signalling pathway plays important roles during development and in cancer. Here we report a Shh-induced epigenetic switch that cooperates with Gli to control transcription outcomes. Before induction, poised Shh target genes are marked by a bivalent chromatin domain containing a repressive histone H3K27me3 mark and an active H3K4me3 mark. Shh activation induces a local switch of epigenetic cofactors from the H3K27 methyltransferase polycomb repressive complex 2 (PRC2) to an H3K27me3 demethylase Jmjd3/Kdm6b-centred coactivator complex. We also find that non-enzymatic activities of Jmjd3 are important and that Jmjd3 recruits the Set1/MLL H3K4 methyltransferase complexes in a Shh-dependent manner to resolve the bivalent domain. In vivo, changes of the bivalent domain accompanied Shh-activated cerebellar progenitor proliferation. Overall, our results reveal a regulatory mechanism that underlies the activation of Shh target genes and provides insight into the causes of various diseases and cancers exhibiting altered Shh signalling

l1-Induced State-Feedback Controller Design for Positive Fuzzy Systems

The problem of l1-induced state-feedback controller design is investigated for positive Takagi-Sugeno (T-S) fuzzy systems with the use of linear Lyapunov function. First, a novel performance characterization is established to guarantee the asymptotic stability of the closed-loop system with l1-induced performance. Then, the sufficient conditions are presented to design the required fuzzy controllers and iterative convex optimization approaches are developed to solve the conditions. Finally, one example is presented to show the effectiveness of the derived theoretical results

Tunnel millisecond-delay controlled blasting based on the delay time calculation method and digital electronic detonators to reduce structure vibration effects.

The reasonable delay time of millisecond-delay blasting using digital electronic detonators can significantly reduce the vibration effects induced by tunnel blasting. This study proposes a method for calculating the delay time for cut holes, easer holes and periphery holes, considering the rocks breaking effect as well as wave superposition theory. And then according to the actual layout diagram of the tunnel holes, the delay time calculation formulas of different holes are put forward. Then the delay times were calculated according to the formulas and applied in the field tests. The velocities, rocks breaking and wave superposition cancellation of the vibration using different delay times are analyzed with digital electronic detonators. Then the optimum delay times of different holes were obtained and applied to New Hongyan tunnel project. The velocity and frequency of the vibration with digital electronic detonators are analyzed, compared with non-electronic detonators. The effects of charge and delay time on the velocity and principal frequency of a blasting seismic wave are discussed. The results indicate that the delay time for the holes must be prioritized to achieve breaking effects in the rock with the simultaneous formation of a new free surface, next considering the wave superposition cancellation. When the delay time of cut holes was 5 ms, the rocks breaking effect and wave superposition cancellation effect both worked well. The velocity of the vibration induced by the cut holes blasting was about only 0.46-0.51 cm/s. When the delay time was 6 ms or much longer, the rocks breaking effect would fail. With regard to the easer holes and periphery holes, the optimum delay time of them were all 5ms. The vertical peak particle velocity was reduced from 2.974 cm/s to 0.901 cm/s with digital electronic detonators. Therefore, the velocity had decreased by 69.70% than non-electronic detonators, which was caused by reducing the single simultaneous explosive charge and setting optimum delay time. The proposed delay time calculation method is demonstrated to be sufficiently accurate and can thus be used as a guideline to reduce tunnel blasting vibrations

On the security of cooperative cognitive radio networks with distributed beamforming

Abstract This paper investigates the secrecy performance of amplify-and-forward (AF)-relaying cooperative cognitive radio networks (CCRNs) over Rayleigh-fading channels. Specifically, we consider practical passive eavesdropping scenarios, where the channel state information of the eavesdropper’s link is not available at the secondary transmitter. In order to avoid interfering with the primary receiver and enhance the secrecy performance, collaborative distributed beamforming is adopted at the secondary relays. Closed-form and asymptotic expressions for the secrecy outage probability of CCRNs in the presence of single and multiple non-colluding eavesdroppers are derived. The asymptotic analysis reveals that the achievable secrecy diversity order of collaborative distributed beamforming with M AF relays is M−1 regardless of the number of eavesdroppers. In addition, simulations are conducted to validate the accuracy of our analytical results

Efficacy and Safety of a Polytetrafluoroethylene Membrane Wrapped a Single Layer of Sirolimus-Eluting Stent in a Porcine Coronary Perforation Model

Background: Covered stents are effective in treating coronary artery perforation (CAP), however, the high rate of immediate device deployment failure and in-stent restenosis have limited the application of the currently covered stents. Methods: We designed a covered stent system consisting of a single layer of drug-eluting stent and a layer of polytetrafluoroethylene (PTFE) membrane wrapped at the outer layer of the stent. The immediate sealing effect of our novel covered stent was observed by using an Ellis type III CAP model. The device’s success was defined as its ability to seal the perforation, assessed by visual estimation and final thrombolysis in myocardial infarction (TIMI) 3 flow. The antiproliferative effect was evaluated in 12 swine, which were randomly assigned to treatment (sirolimus-eluting covered stents) and control (bare metal covered stents) groups. Coronary angiography and optical coherence tomography (OCT) were performed at index procedure, 1- and 6-month after stent implantation. All swine were sacrificed for histopathological analyses at 6-month. Results: The device success rate was 100%. All swine were alive at 6-month follow-up. At 1-month, the treatment group had a larger minimal luminal diameter (MLD) (1.89 ± 0.29 mm vs. 0.63 ± 0.65 mm, p = 0.004) and lower late luminal loss (LLL) (0.47 ± 0.15 mm vs. 1.80 ± 0.34 mm, p < 0.001) compared with control group. At 6-month, the treatment group had a numerically higher MLD (0.94 ± 0.75 mm vs. 0.26 ± 0.46 mm; p = 0.230) and lower LLL (1.43 ± 0.85 mm vs. 2.17 ± 0.28 mm; p = 0.215) compared with control group. Histological analyses revealed the mean plaque area was lower in the treatment group (2.99 ± 0.81 mm2 vs. 4.29 ± 0.77 mm2, p = 0.035) than in the control group. No in-stent thrombosis was observed in either group. Conclusions: In the porcine model of coronary perforation, the PTFE membrane wrapped sirolimus-eluting stent showed a high device success rate in sealing the perforation. The drug-eluting covered stent demonstrated a relatively sustained antiproliferative effect up to 6 months post-implantation

Influence of geographic origin and tissue type on the medicinal chemical compounds of Semiliquidambar cathayensis

Semiliquidambar cathayensis is widely used in traditional Chinese medicine owing its high concentrations of polyphenol, triterpenoidic acid, and flavonoids. This study aimed to explore the impact of geographical origin and tissue type on the contents of chemical compounds of S. cathayensis, as determined by colorimetric and chromatographic methods. Therefore, we quantitively evaluated chemical compounds found in the tissues of various organs of plants collected in six different regions. Overall, we found that geographical origin affected the content of medicinal compounds in S. cathayensis leaves, with plants from Jingzhou county showing the best therapeutic potential. However, no specific correlation was observed with latitude. It is noteworthy that the amount of paeoniflorin and other compounds can be used as biomarkers of geographical origin and tissue type. Most medicinal compounds accumulated mainly in the leaves, whereas ursolic and oleanolic acids accumulated in the roots. These results show that the comprehensive medicinal value of the leaves of S. cathayensis in Jingzhou county is the highest, but the root should be selected first to collect oleanolic acid and ursolic acid