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•A new estimation method for particles mixing curves was proposed.•Mixing curves can be estimated in a short calculation time by the proposed method.•Experimental and estimated mixing ...curves were compared.•It was confirmed that the proposed method can estimate the mixing curves.
A new method for estimating particles mixing curves by simulating the particles behavior for a short period of time using discrete element method (DEM) was developed. The mixing curve is the time variation of the mixing degree, and can be divided into the following two stages: one is the mixing degree increasing stage, and the other is the mixing degree stagnation stage. The mixing curves could be estimated from time variations of mixing and de-mixing rates by assuming that the stagnation occurs when the mixing and de-mixing are balanced. Assuming the mixing and de-mixing rates are represented by the first-order exponential functions, each rate was estimated by the simulations of particles behavior for a short period of time. The estimated mixing curves agree with experimental ones and the proposed estimation method reduced the calculation time to approximately one-fifth of the conventional one that does not use a method to reduce the mixing time. Therefore, the proposed estimation method could estimate the mixing curve in a short period of time.
Analysis of the particle collision behavior in spiral jet milling Kushimoto, Kizuku; Suzuki, Kaya; Ishihara, Shingo ...
Advanced powder technology : the international journal of the Society of Powder Technology, Japan,
20/May , Letnik:
34, Številka:
5
Journal Article
Recenzirano
Odprti dostop
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•DEM-CFD one-way coupling simulation represents the airflow and particle behavior.•Fluid flow in the spiral jet mill is not a simple spiral flow pattern.•Particles are mal-distributed ...near the inner wall of the grinding chamber.•Particles near the top and bottom walls collide at high speeds.•Spiral jet mill could grind the particles circulating near the top and bottom walls.
Collision behaviors of particles in spiral jet milling were analyzed by using a simulation. The motion of the particles was tracked by the discrete element method (DEM), and the air flow was represented by the computational fluid dynamics (CFD). The DEM was coupled with the CFD by a one-way coupling method. The simulated air flow was validated by comparing the fluid velocity field with the measured one in a model experiment. Furthermore, the air flow and particle behaviors in a spiral jet mill used commercially were analyzed by using the simulation. As a result, the particles with a region balancing between centrifugal and radial drag forces could be mainly ground by the high-speed collisions between the particles circulating near the top and bottom walls of the grinding chamber.
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•This study targets for representing of the solid fats.•The ADF model developed to represent elastoplastic deformation and fracture behavior.•The three parameters were determined by ...compression and cutting tests.•The parameters were determined to be as Lps = 0.001, Jsc = 30 kN/m and Ms = 0.25.•Simulated compression and cutting behaviors agree with the experimental behaviors.
A new simulation model, namely, ADEM Ductile Fracture model (ADF model) is developed to represent elastoplastic deformation and fracture behaviors of solid fats. Experimental measurement of the coefficient of plastic starting distance and the yield point affecting the deformation behavior has been obtained by compression test. The fracture distance affecting the fracture behavior has been measured by cutting test. The ADF model shows a good match with the experimentally determined compression and cutting behaviors of the solid fats, and load–strain curves as a function of plate thickness. This confirms that the ADF model could represent the elastoplastic deformation and fracture behaviors of the solid fats.
Osteoarthritis (OA) is a complex disease that affects many people 9, 10, and leads to severe disability. The main risk factors for OA include age, obesity, and joint injury, and OA is more common in ...women 11. The major symptom of OA is pain. Other nervous system changes have been documented including poor proprioception and chronic anxiety 12-14. No efficient treatment or drugs are available, largely because the pathological mechanisms of OA joint damage and the associated pain are not fully understood. Therefore, it is urgent to elucidate the pathomechanisms of OA.Few pain measurements assays have been established for experimental OA models. One goal of this dissertation was to establish an assay to measure knee hyperalgesia in a surgical mouse model, where experimental OA is induced by destabilization of the medial meniscus (DMM). We did this using the Pressure Application Measurement (PAM) device. This study showed how knee hyperalgesia developed and recovered using wild type (WT) mice after DMM and sham surgery. The results showed that DMM mice had more severe knee hyperalgesia than sham mice and that in the sham group hyperalgesia recovered faster than in the DMM group. To confirm that the hyperalgesia is pain-related, this study injected morphine (systemic analgesia) and lidocaine (local analgesia) to WT mice after surgery and confirmed that this reversed hyperalgesia, indicating it is a pain-related behavior. This study also used chemogenetic mice which artificially turns off activation of nociceptors. The result showed that transient chemogenetic blocking of nociceptors temporarily reversed knee hyperalgesia in WT mice, 4 weeks after DMM surgery.In the next part of my work, we aimed to develop an assay to assess proprioception in mice. According to clinical studies, OA patients tend to develop poor proprioception, which causes a higher risk of falls and also limits activity 15. Furthermore, a recent study showed that accuracyxivof proprioception function helps to determine onset and radiographic knee OA 16, 17. To assess proprioception in mice, we used two tests, the beam test and the ladder test, which are one of the known methods used to assess balance in rodents 18, 19. To determine whether the beam or ladder test is appropriate to measure proprioception function, this study used chemogenetics to inhibit parvalbumin (PV)-expressing neurons, which are proprioceptors. We determined whether the beam or the ladder test can assess proprioception function using PV/Pdi 10-week-old mice. The result shows that blocking activity in PV-neurons using CNO in PV/Pdi mice significantly altered (1) tail use duration; (2) frequency of hind paw slip; and (3) time to travel. The beam and ladder test were also conducted in WT mice after DMM or sham surgery. However, the parameters could not find any difference in proprioception ability between naïve, sham, and DMM groups up to 16 weeks after surgery. From these results, the DMM model might not be suitable for proprioception study. This result led us to pursue using the partial meniscectomy (PMX) model, a more severe OA model. Here, we found that the frequency of hind paw slips differentiated between sham and PMX, 12 weeks after surgery. These results show that the PMX model using the ladder test is suitable for proprioception assessment and that proprioception deficits occur at later time points.The third focus for my thesis is anxiety development caused by OA pain, because chronic pain is commonly associated with development of chronic anxiety, as has been described in several diseases such as diabetes, coronary heart disease, and OA 14, 20-22. However, anxiety in OA has not been well studied. Therefore, we used the DMM model to develop a method to assess anxiety-like behavior by the elevated plus maze (EPM) test. According to the results, mice showed increased duration of grooming 12-16 weeks after DMM surgery, comparing to age-matched WTxvnaïve mice. This result suggests that this animal model develops anxiety-like behavior and increasing severity of anxiety gradually up to 16 weeks after surgery.Finally, I examined how CCL2-CCR2 signaling may contribute to the pain-related behaviors described above. Ccr2 null mice were protected from knee hyperalgesia up to 16 weeks after DMM. To understand how CCR2 affects knee hyperalgesia systemically, we used systemic injection of CCR2RA, and found it reversed knee hyperalgesia 4 or 8 weeks after surgery. Local injection of CCR2RA into the OA knee also reversed knee hyperalgesia 7 weeks after surgery. To assess the direct contribution of neuronal CCR2 to development of knee hyperalgesia, we assessed the effect of intra-articular (i.a.) injection of CCL2 into the knee joint space. The result showed that this resulted in transient knee hyperalgesia WT but not in Ccr2 null mice. These results suggest that blocking CCR2 responses at peripheral terminals is sufficient to produce analgesic effects in OA. Recent studies have shown that CCR2 affects anxiety development in anxiety and neuropathic models 7, 23. The results from this study showed that Ccr2 null mice did not develop anxiety behavior up to 16 weeks after DMM surgery, unlike WT mice. This study also showed that anxiety behavior was reversed by systemic injection of CCR2RA 16 weeks after DMM.Overall, these studies indicate that primary knee hyperalgesia assessment by PAM device is a useful method in experimental OA induced by DMM, and that CCL2-CCR2 signaling locally in the joint contributes to knee hyperalgesia in experimental OA. Additionally, we developed a proprioception assay using a beam and a ladder test. We could not detect proprioceptive deficits after DMM surgery, but we did find proprioceptive deficits in the PMX model. Finally, we developed the EPM as a method to detect anxiety associated with OA in the DMM model, and found that CCL2-CCR2 signaling affects anxiety development in this model.
Summary Objective The primary goal of this study was to test the disease-modifying effect of blocking a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-5 with a neutralizing ...monoclonal antibody (mAb) starting 4 weeks after destabilization of the medial meniscus (DMM) in the mouse. We also investigated whether ADAMTS-5 blockade reversed mechanical allodynia and decreased monocyte chemoattractant protein (MCP)-1 production by dorsal root ganglia (DRG) cells. Methods Ten-week old male C57BL/6 mice underwent DMM surgery and were either left untreated or treated with anti-ADAMTS-5 mAb or IgG2c isotype control mAb starting 4 weeks after surgery. Knees were collected for histopathology 4 or 12 weeks later. Mechanical allodynia was monitored biweekly in the ipsilateral hind paw through 16 weeks. DRG were collected and cultured 8 weeks after DMM for analysis of MCP-1 production. Results By 4 weeks after DMM, mild cartilage degeneration was evident in the medial compartment, small osteophytes were present, and subchondral bone sclerosis was established. By 16 weeks after surgery, significant cartilage deterioration was apparent on the medial tibial plateaux and medial femoral condyles, osteophyte size had increased, and subchondral bone sclerosis was maintained. Treatment with ADAMTS-5 mAb from week 4 to 16 after surgery slowed cartilage degeneration and osteophyte growth but did not affect subchondral bone sclerosis. Moreover, ADAMTS-5 blockade resulted in temporary reversal of mechanical allodynia, which correlated with decreased MCP-1 production by cultured DRG cells. Conclusions This study suggests therapeutic efficacy of an ADAMTS-5 mAb in the DMM model, when therapy starts early in disease.
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