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The crystallinity index of cellulose decrystallized with a vibration rod mill was well correlated with input energy of the vibration rod mill. In order to predict the energy, rod ...behavior was simulated by discrete element method (DEM).
Decrystallization of cellulose was performed using a vibration rod mill to increase the reactivity. The decrystallization speed increased with an increase in the number of rods and the crystallinity index of cellulose after pulverization can be uniquely identified by the input energy kWh/kg, which is actual power times pulverization time divided by cellulose mass charged into the vibration rod mill. Therefore, the actual power of the vibration rod mill was calculated using DEM simulation, wherein rods were constructed by connecting spherical particles using the multi-sphere method. The coefficients of friction and restitution were determined based on the movement of the rod in the mill cylinder from the experiments. The power calculated agrees with the actual power. This study suggests that the power of the vibration rod mill can be predicted using DEM and that the crystallinity index can be predicted without experimentation.
Synovial pathology has been linked to osteoarthritis (OA) pain in patients. Microscopic grading systems for synovial changes in human OA have been described, but a standardized approach for murine ...models of OA is needed. We sought to develop a reproducible approach and set of minimum recommendations for reporting of synovial histopathology in mouse models of OA.
Coronal and sagittal sections from male mouse knee joints subjected to destabilization of medial meniscus (DMM) or partial meniscectomy (PMX) were collected as part of other studies. Stains included Hematoxylin and Eosin (H&E), Toluidine Blue (T-Blue), and Safranin O/Fast Green (Saf-O). Four blinded readers graded pathological features (hyperplasia, cellularity, and fibrosis) at specific anatomic locations. Inter-reader agreement of each feature score was determined.
There was acceptable to very good agreement when using 3–4 individual readers. After DMM and PMX, expected medial predominant changes in hyperplasia and cellularity were observed, with fibrosis noted at 12 weeks post-PMX. Synovial changes were consistent from section to section in the mid-joint area. When comparing stains, H&E and T-blue resulted in better agreement compared to Saf-O stain.
To account for the pathologic and anatomic variability in synovial pathology and allow for a more standardized evaluation that can be compared across studies, we recommend evaluating a minimum set of 3 pathological features at standardized anatomic areas. Further, we suggest reporting individual feature scores separately before relying on a single summed “synovitis” score. H&E or T-blue are preferred, inter-reader agreement for each feature should be considered.
Transient Receptor Potential Vanilloid 1 (TRPV1) is a nonselective cation channel expressed by pain-sensing neurons and has been an attractive target for the development of drugs to treat pain. ...Recently, Src homology region 2 domain-containing phosphatase-1 (SHP-1, encoded by
) was shown to dephosphorylate TRPV1 in dorsal root ganglia (DRG) neurons, which was linked with alleviating different pain phenotypes. These previous studies were performed in male rodents only and did not directly investigate the role of SHP-1 in TRPV-1 mediated sensitization. Therefore, our goal was to determine the impact of
overexpression on TRPV1-mediated neuronal responses and capsaicin-induced pain behavior in mice of both sexes. Twelve-week-old male and female mice overexpressing
(Shp1-Tg) and their wild type (WT) littermates were used.
overexpression was confirmed in the DRG of Shp1-Tg mice by RNA
hybridization and RT-qPCR.
and
were found to be co-expressed in DRG sensory neurons in both genotypes. Functionally, this overexpression resulted in lower magnitude intracellular calcium responses to 200 nM capsaicin stimulation in DRG cultures from Shp1-Tg mice compared to WTs.
, we tested the effects of
overexpression on capsaicin-induced pain through a model of capsaicin footpad injection. While capsaicin injection evoked nocifensive behavior (paw licking) and paw swelling in both genotypes and sexes, only WT mice developed mechanical allodynia after capsaicin injection. We observed similar level of TRPV1 protein expression in the DRG of both genotypes, however, a higher amount of tyrosine phosphorylated TRPV1 was detected in WT DRG. These experiments suggest that, while SHP-1 does not mediate the acute swelling and nocifensive behavior induced by capsaicin, it does mediate a protective effect against capsaicin-induced mechanical allodynia in both sexes. The protective effect of SHP-1 might be mediated by TRPV1 dephosphorylation in capsaicin-sensitive sensory neurons of the DRG.
Osteoarthritis (OA) is a leading cause of chronic pain, yet OA pain management remains poor. Age is the strongest predictor of OA development, and mechanisms driving OA pain are unclear. We undertook ...this study to characterize age-associated changes in knee OA, pain-related behaviors, and dorsal root ganglion (DRG) molecular phenotypes in mice of both sexes.
Male or female C57BL/6 mice 6 or 20 months of age were evaluated for histopathologic knee OA, pain-related behaviors, and L3-L5 DRG immune characterization via flow cytometry. DRG gene expression in older mice and humans was also examined.
Male mice at 20 months of age had worse cartilage degeneration than 6-month-old mice. Older female mouse knees showed increased cartilage degeneration but to a lesser degree than those of male mice. Older mice of both sexes had worse mechanical allodynia, knee hyperalgesia, and grip strength compared to younger mice. For both sexes, DRGs from older mice showed decreased CD45+ cells and a significant increase in F4/80+ macrophages and CD11c+ dendritic cells. Older male mouse DRGs showed increased expression of Ccl2 and Ccl5, and older female mouse DRGs showed increased Cxcr4 and Ccl3 expression compared to 6-month-old mouse DRGs, among other differentially expressed genes. Human DRG analysis from 6 individuals >80 years of age revealed elevated CCL2 in men compared to women, whereas CCL3 was higher in DRGs from women.
We found that aging in male and female mice is accompanied by mild knee OA, mechanical sensitization, and changes to immune cell populations in the DRG, suggesting novel avenues for development of OA therapies.
Mechanical plating deposits coatings by cold welding fine particles to a workpiece through ball or shot impact treatment, for example in ball mills. This process offers flexibility in selecting ...material systems because the formation of coatings occurs in the solid state at near room temperature and ambient pressure. However, parametric optimization of the process remains a challenge since many parameters affect the process efficiency. The goal of this study was to numerically investigate the behavior of the balls and a substrate sample in a planetary ball mill and thus to elucidate the mechanisms involved in this mechanical plating treatment. An aluminum substrate with aluminum‑carbon nanotube coating system that was previously investigated experimentally was simulated. A discrete element method model was proposed to perform numerical simulations to predict the energy, frequency, and angle of ball-to-substrate collisions. Measurements were also conducted to determine the friction coefficient necessary for the simulation. The results revealed that small balls caused more frequent and mild collisions with the substrate predominantly in the tangential direction. These collisions are assumed to be the primary contributor to the coating formation. Collisions between large balls and the substrate were less frequent but had greater intensity, and the probability of tangential and normal collisions was approximately equal. The numerical results were qualitatively supported by the as-treated substrate roughness measurements determined in this study.
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•Discrete element method simulation is performed to investigate balls and substrate movements during ball impact treatment.•Friction coefficient, needed for discrete element method simulations, is measured to be 0.5 independently of treatment time.•Tangential ball collisions contribute more to the ball-to-substrate energy transfer than normal ball collisions.•Surface roughness tends to deteriorate with enlargement of ball size due to frequent tangential ball collisions.
Following destabilization of the medial meniscus (DMM), mice develop experimental osteoarthritis (OA) and associated pain behaviors that are dependent on the stage of disease. We aimed to describe ...changes in gene expression in knee-innervating dorsal root ganglia (DRG) after surgery, in order to identify molecular pathways associated with three pre-defined pain phenotypes: “post-surgical pain”, “early-stage OA pain”, and “persistent OA pain”.
We performed DMM or sham surgery in 10-week old male C57BL/6 mice and harvested L3-L5 DRG 4, 8, and 16 weeks after surgery or from age-matched naïve mice (n = 3/group). RNA was extracted and an Affymetrix Mouse Transcriptome Array 1.0 was performed. Three pain phenotypes were defined: “post-surgical pain” (sham and DMM 4-week vs 14-week old naïve), “early OA pain” (DMM 4-week vs sham 4-week), and “persistent OA pain” (DMM 8- and 16-week vs naïve and sham 8- and 16-week). ‘Top hit’ genes were defined as P < 0.001. Pathway analysis (Ingenuity Pathway Analysis) was conducted using differentially expressed genes defined as P < 0.05. In addition, we performed qPCR for Ngf and immunohistochemistry for F4/80+ macrophages in the DRG.
For each phenotype, top hit genes identified a small number of differentially expressed genes, some of which have been previously associated with pain (7/67 for “post-surgical pain”; 2/14 for “early OA pain”; 8/37 for “persistent OA pain”). Overlap between groups was limited, with 8 genes differentially regulated (P < 0.05) in all three phenotypes. Pathway analysis showed that in the persistent OA pain phase many of the functions of differentially regulated genes are related to immune cell recruitment and activation. Genes previously linked to OA pain (CX3CL1, CCL2, TLR1, and NGF) were upregulated in this phenotype and contributed to activation of the neuroinflammation canonical pathway. In separate sets of mice, we confirmed that Ngf was elevated in the DRG 8 weeks after DMM (P = 0.03), and numbers of F4/80+ macrophages were increased 16 weeks after DMM (P = 0.002 vs Sham).
These transcriptomics findings support the idea that distinct molecular pathways discriminate early from persistent OA pain. Pathway analysis suggests neuroimmune interactions in the DRG contribute to initiation and maintenance of pain in OA.
Grinding is one of the most basic and important operations of powder processing. Grinding has been carried out all over the world for a long time. However, the grinding mechanism has not been ...elucidated scientifically. Computer simulation have a possibility to be a useful tool to clarify the grinding mechanism. In this review, new simulation methods for particle breakage were introduced, and the advantage of each method was discussed. Prediction of grinding results based on the impact energy has an advantage of calculation load, however, it is difficult to analyze the grinding process. On the other hand, direct simulation of particle breakage can analyze the grinding process. It is necessary to choose an appropriate method according to the purpose.
Summary Objective Microgliosis, the activation of microglial cells, is thought to contribute to synaptic transmission in the dorsal horn and thereby promote chronic pain. The primary aim of this ...study was to document the temporal profile of dorsal horn microgliosis after destabilization of the medial meniscus (DMM) in wild type (WT) and Adamts5 null mice. Since neuronal fractalkine (CX3CL1) contributes to microgliosis, we assessed its release from dorsal root ganglia (DRG) cultures after DMM. Design DMM or sham surgery was performed in the right knee of 10-week old male WT, CX3CR1-GFP, or Adamts5 null C57BL/6 mice. Hind paw mechanical allodynia was monitored using von Frey fibers. L4 dorsal horn microgliosis was assessed 4, 8 and 16 weeks after surgery, based on the morphology of Iba1-immunoreactive microglia. DRG cells (L3–L5) were cultured and supernatants collected for fractalkine (FKN) ELISA. Results In WT mice, numbers of activated microglia were increased 8 and 16 weeks, but not 4 weeks, after DMM but not sham surgery. DRG cultures showed increased basal FKN release at 8 and 16 weeks. Adamts5 null mice did not develop mechanical allodynia up to 16 weeks after DMM. Accordingly, DRG cultures from these mice did not exhibit increased FKN release and dorsal horn microgliosis did not occur. Conclusion DMM surgery leads to late stage dorsal horn microgliosis. The temporal correlation with DRG FKN release suggests it may contribute to microgliosis. Reduced microgliosis in Adamts5 null mice, which are protected from joint damage and associated mechanical allodynia after DMM, suggests that microgliosis is associated with joint damage and accompanying persistent pain.
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•We propose a new model, named Layer structure model, to estimate the macroscopic permittivity of particulate composite materials.•The Layer structure model can consider the particle ...size distribution.•We develop a new method for estimating the filler dispersion state by applying the Layer structure model.•The validaties of the model and method are confirmed by comparing with experiments, respectively.
A new model for estimating macroscopic permittivity was proposed to predict filler particles' dispersion states in a particulate composite material. In the model, the estimation targets are randomly packed composite materials. The composite materials were represented as a cluster of unit cells. A proposed layer structure model connected the unit cells. The macroscopic permittivity was estimated by calculating the synthetic capacity of the cluster. The proposed model was validated by comparisons between estimated and measured macroscopic permittivity of several particulate composite materials. It was also identified that the proposed model could estimate the permittivity more accurately than an existing theoretical equation's one due to considering the effects for the dispersion states of filler particles. Furthermore, it was indicated that the proposed model could also estimate the dispersion states of filler particles by the measured permittivity. The applicability of the method was confirmed by comparisons between estimated and experimental dispersion states of filler particles.
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