ORY-1001 Suppresses Cell Growth and Induces Apoptosis in Lung Cancer Through Triggering HK2 Mediated Warburg Effect

ORY-1001, an inhibitor of covalent lysine (K)-specific demethylase 1A (KDM1A), has been used as a therapy for the treatment of acute leukemia. However, the underlying mechanisms of anticancer are still not fully elucidated. Here, we report that KDM1A is highly expressed in lung cancers, where it appears to drive aggressive growth. Furthermore, lung cancer patients with higher KDM1A levels have worse survival outcomes than patients with lower KDM1A levels. Interestingly, ORY-1001significantly inhibited the cell proliferation, colony formation, cell cycle, and induced apoptosis, by regulating the Warburg effect through controlling Hexokinases 2 (HK2) expression. In summary, these results indicate that ORY-1001 could inhibit the growth of lung cancer cells via regulating the Warburg effect by controlling HK2

Precursory characteristics and disaster prevention of rock burst in roadway excavation in steeply inclined extra-thick coal seam

With the gradual coal mining of deep rock burst mine, the impact accompanying roadway excavation becomes more and more intense. Aiming at the problem of effective prevention and control of rock burst in roadway excavation, taking the steep seam mine in the Wudong Coal Mine as an example, the temporal and spatial precursor characteristics of rock burst in roadway excavation were analyzed by microseismic monitoring. Combined with the numerical simulation analysis of stress and energy changes in roadway excavation, the mechanism of rock burst in roadway excavation was revealed, and the prevention and control strategy of rock burst in steeply inclined extra-thick coal seam roadway was put forward, which was verified by field engineering practice. The results show that the total energy of microseisms is extremely low for 2−5 days or there is an energy latency of at least 4 days before the rock burst occurs due to roadway excavation in steeply inclined extra-thick coal seam. Within 5 days before rock burst occurs, there is a high-frequency fluctuation period of maximum energy ratio for more than 3 days. There is an obvious lack of earthquake before the rock burst occurs, and the occurrence position is concentrated in the range of minimum value of microseismic energy near the heading face, or in the range of minimum value of microseismic frequency near the extreme value of microseismic energy, and the rock burst event is located in the area with high impact deformation energy index. The hard overburden structure of horizontal sublevel fully mechanized caving mining in steeply inclined extra-thick coal seam is not easy to break, which makes the stress concentration on both sides of upper horizontal goaf exist in roadway excavation. The stress between the front of the heading face and the bottom of the roadway squeezed by the roof and floor strata is concentrated and the energy accumulation is remarkable. With the increase of the heading depth of the roadway, the stress concentration and energy accumulation are further enhanced, which is easy to induce dynamic disasters such as rock burst. The prevention and control strategies of rock burst was established through comprehensive analysis, which consist of face blasting pressure relief, roadway drilling pressure relief and reinforcement support, and scaffolding in complex areas. Combined with the temporal and spatial precursory anomalies of rock burst, it provides an opportunity to strengthen the unloading pressure in time. Through the pressure relief of working face and roadway, the accumulated microseismic energy of more than 1×105 J per day did not occur during the excavation. After the support was optimized and the complex area was protected, the daily average microseismic energy of roadway excavation decreased to 2.2 kJ, and the proportion of microseismic events above 1 kJ decreased, and the overall section of roadway was flat

Temporal and spatial evolution law of microseisms and induced impact mechanism in complex spatial structure area of steep and extremely thick coal seam

The occurrence of coal mine rock burst disasters is closely related to the spatial structure, especially in the complex spatial structure area. It is of great significance to master the law of coal and rock catastrophe and reveal its mechanism in the complex spatial structure area of coal seam mining for the prevention and control of rock burst. Taking the Wudong Coal Mine as the research background, using numerical simulation, micro-seismic monitoring, theoretical analysis and other methods, the abnormal size effect of rock pillar stress is studied, the temporal and spatial evolution law of microseisms in the complex spatial structure area is analyzed, the mechanism of rock burst under the complex spatial structure is revealed, and the impact risk in the different areas of coal mining is evaluated. The research results show that: ① The steeply inclined rock pillar with narrower thickness and higher exposed height has stronger prying effect, and the abnormal stress of rock thickness variation forms five divisions. ② The area with narrower rock pillar thickness has more micro-seismic frequency, higher energy, stronger spatio-temporal activity and higher dispersion. The high stress region, the stress gradient region and the stress plateau region show the micro-seismic response characteristics of “low frequency-high energy”, “high frequency-high energy” and “low frequency-low energy” in turn. ③ The micro-seismic events in special spatial structure area are clustered and the energy level increases, and the temporal and spatial activity and dispersion increase sharply. This feature is more obvious especially at the edge of the structure, the energy accumulation and release rate increases, and the probability and intensity of rock burst are higher. The micro-seismic activity of special spatial structures located in the narrower area of rock pillars is more acute. ④ The narrower the thickness of rock pillar (the greater the height of coal pillar), the faster the growth rate of bending moment and energy in the depth of rock pillar, and the higher the impact risk. According to the strength effect of structural plane, it is inferred that the fault zone has slip and dislocation, and fault zone is the dominant area for energy accumulation and release. It is revealed that the mechanism of rock burst is the joint action of high static load and low critical load. The impact risk in the different areas of coal mining is evaluated based on stress concentration characteristics

Control of a Tilting Hexacopter under Wind Disturbance

Multicopters are well suited for executing fast maneuvers with high velocity, but they are still affected by the external atmospheric environment because attitude and position cannot be independently controlled. In this paper, we present a novel hexacopter which improves the wind resistance and strong coupling between attitude control and position control. The copter is designed such that the rotor sections can tilt around their respective arm axes. We present the aerodynamic methods to analyze the system dynamics model in windy environments. The entire system is decomposed into six loops based on the model, and the presented flight controller uses the ADRC method to consider both the attitude and the position. The controller introduces the extended state observer to estimate the white noise and wind disturbance. We use the nonlinear state error feedback law to control the output with disturbance compensation. Finally, we linearize the control allocation matrix that the controllers output directly mapped to the rotor velocities and tilting angles. The new theoretical results are thoroughly validated through comparative experiments

A Preliminary Study of Laser Directional Solidification for Potential Use in the Repair of Damaged Aviation Turbine Blades

To achieve directional solidification repair of damaged aviation turbine blades, the directional growth repair layer was prepared using a Nd:YAG laser on the surface of superalloy DZ-22. A scanning electron microscope (SEM) was used to observe the microstructure. The element distribution was analyzed and the microhardness of the sample was measured. The results showed that primary dendrite size was proportional to the current and the pulse-width, and inversely proportional to the scanning speed. No obvious macrosegregation of the repair zone was evident. The zone exhibited a finer microstructure than the substrate and had a smaller columnar crystal size, which was approximately two orders of magnitude smaller than the substrate. The micro-segregation between the centers and the edges of the dendrites and in between adjacent dendrites and a decrease in microhardness from the repair zone (455 HV) to the substrate also were observed

ARSS: A Novel Aerial Robot Performs Tree Pruning Tasks

In this article, we present a novel aerial robot with a suspended saw (ARSS) for pruning trees that are close to electric power lines. The Robot’s movement process includes free flight and aerial pruning. We first established a dynamic model and designed a controller based on the Active Disturbance Rejection Control (ADRC) on the model. Aiming at the problem of saw swing and residual oscillation during the free flight movement, we adopt the linear state feedback to design a swing angle controller. Finally, we use Matlab/Simulink and CoppeliaSim for simulation, and the simulation results verify the effectiveness and feasibility of the controller