Breakage behavior of irregular shaped particles was analyzed by ADEM (Advanced Distinct Element Method). This paper attempted to determine ADEM parameters to represent breakage behavior of irregular ...shaped particles. Compression test have been carried out experimentally to obtain information about particle breakage. In the simulation, joint spring coefficient and maximum strain were parameters for reproducing the experimental results. Pumice was chosen as a sample, and the shape was measured by 3D scanner. Obtained 3D data was converted to cluster particle which is agglomerate of primary particles. Simulation results were compared to experimental results from the view point of load-displacement curve and the shape of samples after breakage. In the simulation, the gradient of load in response to displacement obviously increases with an increase in the joint spring coefficient. Compressive strength increases with an increase in the maximum strain. Impact test was carried out to confirm whether the parameters determined by compression test can also be applied to other breakage behavior. In the impact test, a stainless steel ball was free-falling on the cluster particle from 200 or 400 mm in drop height. In experiment, the number of dropping times needed for breakage decrease with increase in falling height. Same tendency could be observed in the simulation. Breakage behavior in impact test could express by ADEM simulation using the simulation parameters obtained from compression test. According to these results, it is suggested that ADEM has a possibility to become a useful tool to analyze particle breakage behavior.
A new simulation model for the analysis of solid to liquid phase transition behaviors inside the blast furnace was developed in this study. The solid state is treated by ADEM (Advanced Distinct ...Element Method) and the liquid state is treated by SPH (Smoothed particle Hydrodynamics). The intermediate state is treated by overlapped calculation of both ADEM and SPH. Numerical examinations for the analysis of several phenomena such as dam brake flow, droplet deformation due to the contact angle and phase transition were performed. The validity of the proposed model was confirmed by comparison with the experimental results of the motion of the leading edge in collapse of a water column in the dam break test. The phase transition behavior of ore was observed experimentally using horizontal furnace. The deformation started at about 1200°C from the upper corner of sample pellet became round, and melted down to the whole with slight contraction. A similar behavior is also can be seen in the simulation by appropriately setting the relationship between the temperature and the joint spring coefficient. These results are indicated that the developed model has possibility to clarify the burdens behavior including the phase transition inside the blast furnace.
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•Particle density strongly has an effect on mixing behavior in rotating drum.•The segregation of particles is obviously observed in the experiment and the DEM simulation.•Lower ...density particles could move easily in comparison with higher density particles.•The inhomogeneity of mixed state was improved by using a rotating drum with lifters.
The mixing behavior of particles in a rotating drum mixer (RDM) was analyzed by experiment and Distinct Element Method (DEM) simulation in order to discuss the effect of particle density. In both of the experiment and the DEM simulation, mixing behavior of alumina (3600kg/m3) and stainless steel (7930kg/m3) particles in the rotating drum was observed and mixing degree was evaluated. In the experiment, most of the alumina particles with lower density exist close to the container wall and in the vicinity of the surface of particle bed. The mixing behavior of DEM simulation is comparatively similar to that of the experiment, and it is confirmed that the DEM simulation has high reliability for simulating the mixing behavior. The DEM simulation was used to analyze the influence of particle density on mixing behavior and to make clear the segregation mechanism in a binary system. When the particle density ratio is larger, the mixing behavior in a rotating drum is strongly affected by the ratio. In order to analyze the mechanism of the segregation quantitatively, the new index related with the mobility of particles was developed. This result of the index indicated that the particles with lower density could move easily in comparison with higher density particles, and the difference between the mobility of those materials cause the segregation. The rotating drum with lifters (RDM_L) was adopted to improve the mixing state of particles, and particles behavior in the drum was simulated by the DEM. The mixing state of particles becomes comparatively uniform and the particle segregation would not be observed. These results indicate that lifters could control the behavior of higher and lower density particles and enhance particles mixing.
Mechanochemical reactions can be induced in a solution by the collision of balls to produce high-temperature and high-pressure zones, with the reactions occurring through a dissolution-precipitation ...mechanism due to a change in solubility. However, only a fraction of the impact energy contributes to the mechanochemical reactions, while the rest is mainly consumed by the wear of balls and the heat generation. To clarify whether the normal or tangential component of collisions makes a larger contribution on the reaction, herein we studied the effect of collision direction on a wet mechanochemical reaction through combined analysis of the experimental reaction rates and simulated ball motion. Collisions of balls in the normal direction were found to contribute strongly to the wet mechanochemical reaction. These results could be used to improve the synthesis efficiency, predict the reaction, and lower the wear in the wet mechanochemical reactions.
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•Persistent homology is applied to the structural analysis of wet powder compacts.•Structural homogeneity affects the elastic modulus of wet powder compacts.•An empirical equation for ...predicting the elastic modulus of wet powder compacts is proposed.
This study applies persistent homology (PH) to the structural analysis of wet powder compacts to clarify the effect of packing structure on the elastic modulus, and proposes an equation for the relationship between saturation and elastic modulus based on the index of structural homogeneity. The relationship between the saturation and the elastic modulus was experimentally obtained by compression tests of wet powder compacts. The elastic modulus decreased linearly with increasing saturation, but the slope was different depending on the packing structure of compacts which were made from high purity alumina with different particle size distributions. PH was applied to the packing structure of particles of different diameters calculated by DEM simulation to evaluate the packing structure. The features of each packing structure were extracted by PH, and the index of structural homogeneity was obtained. A new empirical equation is proposed which can predict the relationship between the elastic modulus and the saturation considering structural homogeneity, specific surface area, surface tension, and porosity as the main factors affecting the elastic modulus in the partially saturated state. These results indicate that PH analysis is effective to evaluate the packing structure and that this method may predict the mechanical properties of wet powder compacts.
Non-opioid targets are needed for addressing osteoarthritis pain, which is mechanical in nature and associated with daily activities such as walking and climbing stairs. Piezo2 has been implicated in ...the development of mechanical pain, but the mechanisms by which this occurs remain poorly understood, including the role of nociceptors. Here we show that nociceptor-specific Piezo2 conditional knock-out mice were protected from mechanical sensitization associated with inflammatory joint pain in female mice, joint pain associated with osteoarthritis in male mice, as well as both knee swelling and joint pain associated with repeated intra-articular injection of nerve growth factor in male mice. Single cell RNA sequencing of mouse lumbar dorsal root ganglia and in situ hybridization of mouse and human lumbar dorsal root ganglia revealed that a subset of nociceptors co-express Piezo2 and Ntrk1 (the gene that encodes the nerve growth factor receptor TrkA). These results suggest that nerve growth factor-mediated sensitization of joint nociceptors, which is critical for osteoarthritic pain, is also dependent on Piezo2, and targeting Piezo2 may represent a therapeutic option for osteoarthritis pain control.
We aimed to explore activation of the Notch signaling pathway in knee-innervating lumbar dorsal root ganglia (DRG) in the course of experimental osteoarthritis (OA) in mice, and its role in knee ...hyperalgesia.
Cultured DRG cells were stimulated with the TLR4 agonist, lipopolysaccharide (LPS). Notch signaling in the cells was either inhibited with the γ-secretase inhibitor, DAPT, or with soluble Jagged1, or activated through immobilized Jagged1. CCL2 production was analyzed at mRNA and protein levels. In in vivo experiments, knee hyperalgesia was induced in naïve mice through intra-articular (IA) injection of LPS. The effect of inhibiting Notch signaling was examined by pre-injecting DAPT one hour before LPS. OA was induced through surgical destabilization of the medial meniscus (DMM) in male C57BL/6 mice. Gene expression in DRG was analyzed by qRT-PCR and RNAscope in situ hybridization. Activated Notch protein (NICD) expression in DRG was evaluated by ELISA and immunofluorescence staining. DAPT was injected IA 12 weeks post DMM to inhibit Notch signaling, followed by assessing knee hyperalgesia and CCL2 expression in the DRG.
In DRG cell cultures, LPS increased NICD in neuronal cells. Inhibition of Notch signaling with either DAPT or soluble Jagged1 attenuated LPS-induced increases of Ccl2 mRNA and CCL2 protein. Conversely, activating Notch signaling with immobilized Jagged1 enhanced these LPS effects. In vivo, IA injection of LPS increased expression of Notch genes and NICD in the DRG. Pre-injection of DAPT prior to LPS alleviated LPS-induced knee hyperalgesia, and decreased LPS-induced CCL2 expression in the DRG. Notch signaling genes were differentially expressed in the DRG from late-stage experimental OA. Notch1, Hes1, and NICD were increased in the neuronal cell bodies in DRG after DMM surgery. IA administration of DAPT alleviated knee hyperalgesia post DMM, and decreased CCL2 expression in the DRG.
These findings suggest a synergistic effect of Notch signaling with TLR4 in promoting CCL2 production and mediating knee hyperalgesia. Notch signaling is activated in knee-innervating lumbar DRG in mice with experimental OA, and is involved in mediating knee hyperalgesia. The pathway may therefore be explored as a target for alleviating OA pain.
C-C chemokine receptor 2 (CCR2) signaling plays a key role in pain associated with experimental murine osteoarthritis (OA) after destabilization of the medial meniscus (DMM). Here, we aimed to assess ...if CCR2 expressed by intra-articular sensory neurons contributes to knee hyperalgesia in the early stages of the model.
DMM surgery was performed in the right knee of 10-week-old male wild-type (WT), Ccr2 null, or Ccr2
C57BL/6 mice. Knee hyperalgesia was measured using a Pressure Application Measurement device. CCR2 receptor antagonist (CCR2RA) was injected systemically (i.p.) or intra-articularly (i.a.) at different times after DMM to test its ability to reverse knee hyperalgesia. In vivo Ca
imaging of the dorsal root ganglion (DRG) was performed to assess sensory neuron responses to CCL2 injected into the knee joint cavity. CCL2 protein in the knee was measured by ELISA. Ccr2
mice and immunohistochemical staining for the pan-neuronal marker, protein gene product 9.5 (PGP9.5), or the sensory neuron marker, calcitonin gene-related peptide (CGRP), were used to visualize the location of CCR2 on intra-articular afferents.
WT, but not Ccr2 null, mice displayed knee hyperalgesia 2-16 weeks after DMM. CCR2RA administered i.p. alleviated established hyperalgesia in WT mice 4 and 8 weeks after surgery. Intra-articular injection of CCL2 excited sensory neurons in the L4-DRG, as determined by in vivo calcium imaging; responses to CCL2 increased in mice 20 weeks after DMM. CCL2, but not vehicle, injected i.a. rapidly caused transient knee hyperalgesia in naïve WT, but not Ccr2 null, mice. Intra-articular CCR2RA injection also alleviated established hyperalgesia in WT mice 4 and 7 weeks after surgery. CCL2 protein was elevated in the knees of both WT and Ccr2 null mice 4 weeks after surgery. Co-expression of CCR2 and PGP9.5 as well as CCR2 and CGRP was observed in the lateral synovium of naïve mice; co-expression was also observed in the medial compartment of knees 8 weeks after DMM.
The findings suggest that CCL2-CCR2 signaling locally in the joint contributes to knee hyperalgesia in experimental OA, and it is in part mediated through direct stimulation of CCR2 expressed by intra-articular sensory afferents.
Objective
To determine whether selected damage‐associated molecular patterns (DAMPs) present in the osteoarthritic (OA) joints of mice excite nociceptors through Toll‐like receptor 4 (TLR‐4).
Methods
...The ability of S100A8 and α2‐macroglobulin to excite nociceptors was determined by measuring the release of monocyte chemoattractant protein 1 (MCP‐1) by cultured dorsal root ganglion (DRG) cells as well as by measuring the intracellular calcium concentration (Ca2+i) in cultured DRG neurons from naive mice or from mice that had undergone surgical destabilization of the medial meniscus (DMM) 8 weeks previously. The role of TLR‐4 was assessed using TLR‐4–/– cells or a TLR‐4 inhibitor. The Ca2+i in neurons within ex vivo intact DRGs was measured in samples from Pirt‐GCaMP3 mice. Neuronal expression of the Tlr4 gene was determined by in situ hybridization. DMM surgery was performed in wild‐type and TLR‐4–/– mice; mechanical allodynia was monitored, and joint damage was assessed histologically after 16 weeks.
Results
DRG neurons from both naive and DMM mice expressed Tlr4. Both S100A8 and α2‐macroglobulin stimulated release of the proalgesic chemokine MCP‐1 in DRG cultures, and the neurons rapidly responded to S100A8 and α2‐macroglobulin with increased Ca2+i. Blocking TLR‐4 inhibited these effects. Neurons within intact DRGs responded to the TLR‐4 agonist lipopolysaccharide. In both of the calcium‐imaging assays, it was primarily the nociceptor population of neurons that responded to TLR‐4 ligands. TLR‐4–/– mice were not protected from mechanical allodynia or from joint damage associated with DMM.
Conclusion
Our experiments suggest a role of TLR‐4 signaling in the excitation of nociceptors by selected DAMPs. Further research is needed to delineate the importance of this pathway in relation to OA pain.
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•The density distribution during die bonding is formed by die loading speed.•The formation of non-uniform density distribution was reproduced by SPH simulation.•The local shear stress ...difference is the cause of the density distribution.•Since the paste was a shear-thinning fluid, an X-shaped distribution was formed.
The flow behavior of silver paste during die bonding was analyzed by numerical simulation to clarify the formation mechanism of coarse-dense inhomogeneous distribution of silver particles in a die-attach layer. Depending on the loading speed of a die, silver particles in the paste flow and form a coarse-dense distribution under a die. The microstructure of the paste before sintering was observed by X-ray computer tomography (X-ray CT) and Scanning Electron Microscope (SEM). At a slow loading speed of 1.0 μm/s, the paste is densely packed with silver particles along the diagonal of the die. A coarse structure was observed in the other area of the paste. On the other hand, at a high loading speed of 60.0 μm/s, there was no clear segregation and the paste layer has an almost uniform structure. The SPH method was used to calculate the flow behavior of particles in the paste, and the flow velocity and shear stress of the paste were calculated. The paste velocity and shear stress in the region along the diagonal of the die is smaller than those in other area of the die. A comparison of the shear stress applied to the paste at different loading speeds showed that the smaller the loading speed, the larger the value of summation of shear stress. The difference between the maximum and minimum shear stress in a lateral direction through the center of the die increases with decreasing of loading speed. Thus, a large difference in local shear stress acting on the paste causes the formation of coarse-dense structure of the silver paste. It was found that it is necessary to eliminate local differences in the shear stress acting on the paste in order to achieve uniform joint the silver paste to the substrate without forming a coarse-dense structure.
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