The YAP and TAZ paralogs are transcriptional co-activators recruited to target sites by TEAD proteins. Here, we show that YAP and TAZ are also recruited by JUNB (a member of the AP-1 family) and ...STAT3, key transcription factors that mediate an epigenetic switch linking inflammation to cellular transformation. YAP and TAZ directly interact with JUNB and STAT3 via a WW domain important for transformation, and they stimulate transcriptional activation by AP-1 proteins. JUNB, STAT3, and TEAD co-localize at virtually all YAP/TAZ target sites, yet many target sites only contain individual AP-1, TEAD, or STAT3 motifs. This observation and differences in relative crosslinking efficiencies of JUNB, TEAD, and STAT3 at YAP/TAZ target sites suggest that YAP/TAZ is recruited by different forms of an AP-1/STAT3/TEAD complex depending on the recruiting motif. The different classes of YAP/TAZ target sites are associated with largely non-overlapping genes with distinct functions. A small minority of target sites are YAP- or TAZ-specific, and they are associated with different sequence motifs and gene classes from shared YAP/TAZ target sites. Genes containing either the AP-1 or TEAD class of YAP/TAZ sites are associated with poor survival of breast cancer patients with the triple-negative form of the disease.
Anchor cables (bolts) act as the main support system and play an important role in improving the rock burst resistance and stability of the roadway surrounding the rock. In this study, the dynamic ...response characteristics of the roadway surrounding the rock and the support system under different shock intensities were investigated. The following findings were obtained. The stress wave propagation process under dynamic shock was divided into a stress vibration initiation stage, a stress fluctuation stage, and a stress adjustment stage. In the stress vibration initiation stage, the surface mass of the roadway surrounding the rock started to vibrate, and the pretension of the anchor cables (bolts) was reduced; in the stress fluctuation stage, the failure of the roadway surrounding the rock intensified, and the anchor cables (bolts) were damaged to some extent; and in the stress adjustment stage, the roadway deformation of the surrounding rock and the axial forces of the anchor cables (bolts) tended to stabilize. As the dynamic shock intensity increased, the vibration velocity, displacement increment, and acceleration amplitude of the mass of the roadway surrounding the rock increased exponentially. The critical shock energy of the roadway surrounding the rock was 105 J, above which the damage to the rock was aggravated. The larger the pretension of the anchor cables (bolts) was and the higher the dynamic shock intensity was, the more severe the damage to the anchor cables (bolts) was. Given the dynamic response characteristics of the roadway surrounding the rock and support elements under shock, a full anchor cable yielding support technology is proposed to effectively control the stability of the roadway surrounding the rock under dynamic shock, providing a reference for the construction of the support systems for preventing rock bursts in similar roadways.
MafB (a bZIP transcription factor), ß-catenin (the ultimate target of the Wnt signal transduction pathway that acts as a transcriptional co-activator of LEF/TCF proteins), and WDR77 (a ...transcriptional co-activator of multiple hormone receptors) are important for breast cellular transformation. Unexpectedly, these proteins interact directly with each other, and they have similar genomic binding profiles. Furthermore, while some of these common target sites coincide with those bound by LEF/TCF, the majority are located just downstream of transcription initiation sites at a position near paused RNA polymerase (Pol II) and the +1 nucleosome. Occupancy levels of these factors at these promoter-proximal sites are strongly correlated with the level of paused Pol II and transcriptional activity.
Responding to severe surrounding rock deformation failures and other problems in roadways in western China with large mining heights and intense mining, the work presented in this paper studied the ...mechanism of surrounding rock deformation failures in roadways with dynamic pressure through field investigations, theoretical analysis, and numerical simulation. According to the research findings, mining roadway deformation failures are affected by roadway layout orientation, working face mining intensity, and dynamic load disturbances from roof breakage. Coal pillars, as bridges connecting the roof and floor, constitute the energy transfer path near roadways surrounding rock, and an unreasonable coal pillar size and lateral overhanging roof structure may aggravate static load energy accumulation in the roadway surrounding rock. Roadway protection with small or large coal pillars may increase elastic energy loss in the energy transfer path; a reasonable size of small and large coal pillars is 15 m and 35 m, respectively. Using roof cutting for pressure relief may reduce the elastic energy of roadway surrounding rock by 14.35-26.33% during primary mining and 21.57-29.31% during secondary mining, thereby reducing the static load elastic energy in the surrounding rock and improving the stability of roadway surrounding rock.
This paper presents an innovative method for using foam concrete as a typical building material for soft structures in underground coal mines subjected to dynamic loading. To understand the behaviour ...of foam concrete under impact loading, a total of 30 specimens with a diameter of 50 mm and a height of 50 mm were experimentally tested using a 75 mm diameter split Hopkinson pressure bar (SHPB) device. The key parameters investigated in the present study included the type of foam concrete (fly ash and sand), the density of foam concrete (1000, 1200 and 1400 kg/m3), and the impact velocity (3.0, 4.0, 5.0, 6.0, and 7.0 m/s). Six specimens were also tested under static loading for comparison. The stress-strain curve of foam concrete under impact loading showed three stages, started with a linear elastic stage, followed by a yield stage and ended with a pore wall destruction stage. The test results also indicated that the dynamic increase factor, ultimate compressive strength, tenacity, and specific energy absorption increase with the strain rate under the same density. In particular, both the failure model and the behaviour of foam concrete were affected by the impact velocity. The findings of this research provide a reference for further research on the application of foam concrete in underground coal mines.
Charcot-Marie-Tooth disease 2C (CMT2C) and scapuloperoneal spinal muscular atrophy (SPSMA) are different clinical phenotypes of TRPV4 mutation. The mutation of p.R316C has been reported to cause ...CMT2C and SPSMA separately.
Here, we reported a Chinese family harboring the same p.R316C variant, but with an overlap syndrome and different clinical manifestations. A 58-year-old man presented with severe scapula muscle atrophy, resulting in sloping shoulders. He also exhibited distinct muscle atrophy in his four limbs, particularly in the lower limbs. The sural nerve biopsy revealed severe loss of myelinated nerve fibers with scattered regenerating clusters and pseudo-onion bulbs. Nerve conduction study showed axon damage in both motor and sensory nerves. Sensory nerve action potentials could not be evoked in bilateral sural or superficial peroneal nerves. He was diagnosed with Charcot-Marie-Tooth disease type 2C and scapuloperoneal muscular atrophy overlap syndrome, whereas his 27-year-old son was born with clubfoot and clinodactyly. Electromyogram examination indicated chronic neurogenic changes and anterior horn cells involvement. Although there was no obvious weakness or sensory symptoms, early SPSMA could be considered for him.
A literature review of the clinical characteristics in CMT2C and SPSMA patients with TRPV4 mutation suggested that our case was distinct due to the overlap syndrome and phenotype variation. Altogether, this case broadened the phenotype spectrum and provided the nerve biopsy pathological details of TRPV4-related neuropathies.
The mechanical properties of foam concrete with sand at different low temperatures and different strain rates were studied. Foam concrete with sand at low temperatures (−10, −20, and −30°C) were ...tested using a split Hopkinson pressure bar (SHPB) apparatus with different impact pressures (0.15, 0.20, 0.25, 0.30, and 0.35 MPa). The experimental results show that the porosity of sand containing foam concrete with a density of 1,000, 1,200, 1,400 kg/m
3
decreases with increasing density. In the same strain rate range, the lower the temperature of the same density foam concrete with sand, the greater the ultimate compressive strength. The change in strength was caused by the presence of pore water or ice in the foam concrete with sand in low-temperature conditions. The dynamic compressive strength of foam concrete with sand decreases with increasing strain rate. The macroscopic failure of foam concrete was closely related to the energy absorption and dependent on the rate. The total dissipated energy of the low-temperature foam concrete with sand increased linearly as the temperature decreased. The research results provide the low-temperature mechanical properties of foam concrete with sand, which provides a reference for the application of foam concrete with sand.
Mining activities are key triggers for strong mine earthquakes and even rock bursts in coal mines. This study explores the impact of mining speed on the overlying strata’s deformation and energy ...release through theoretical analysis, numerical simulation, and the digital speckle method. The temporal and spatial evolution characteristics of the impact energy during mining are simulated. The digital speckle method illustrates a positive correlation between rapid mining and increased fracture block degree of overburden rock and roof separation, confirming that accelerated mining speed extends the fracture distance of the stope. Furthermore, numerical simulations establish that both the energy associated with overlying rock breaking and the frequency of energy occurrence events are amplified during rapid mining, in contrast to slow mining. This observation corroborates that escalating mining speed augments the energy dispensed by the breaking of the upper rock. Consequently, this escalation induces a transformation in the energy levels of mine earthquakes, culminating in a heightened incidence of large-energy mine earthquakes.
This paper studies the evolution and control of surrounding rock under different pressure relief support conditions in mine roadways in which rockburst events have occurred. The evolution of ...fractures in the surrounding rock was determined from borehole images obtained with a digital panoramic borehole camera, and the surface displacement due to the rockburst events in the mine roadway was measured. According to the existing problems of the original support system of the roadway, a new coupled support system to prevent rockburst events in mine roadways was proposed, resolving both the pressure relief and support of the roadway. Field measurements indicate that the effect on the roadway under the coupled method of pressure relief and support was more satisfactory than that under the original support system. With the coupled support method, the surface displacement of the roadway was approximately 0.6 m, fractures were distributed only in the soft structures and bolt anchorage areas, and the maximum depth of the fractures was 2.95 m. By contrast, under the original support system, fractures were distributed throughout the roadway surrounding rock, and the maximum depth of fractures was 6.75 m. This coupled roadway support technology of pressure relief and support effectively maintains the stability of the rock surrounding the roadway and ensures the safety of the working face. The research results can provide a reference for damage prevention and support of mine roadways prone to rockburst events.
Rock bursts have become one of the worst disasters in deep mines, and the safety of roadways is affected by stress waves generated when hard roofs fracture. Pictures of a mine site were collected ...using the Hujiahe mine as a case study. The damage characteristics of the roadway were analyzed and the damage process was reproduced using numerical simulation software. The attenuation characteristics of the strength of the shock wave as it passes from the impact shock source to the roadway are summarized. Based on the stress wave transmission mechanism and geological characteristics, a “shock wave attenuation model through rock formations“ was established to analyze the transmission characteristics of impact stress under the composite roof structure. The strength criterion and energy balance equation for roadway damage under the action of shock waves are derived. This work provides a reference for roadway support under similar conditions and can be generalized and applied elsewhere.
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