Microstructure and mechanical properties of aluminum alloy 2024 (Al2024)/few-layer graphene (FLG) composites produced by ball milling and hot rolling have been investigated. The presence of dispersed ...FLGs with high specific surface area significantly increases the strength of the composites. The composite containing 0.7vol.% FLGs exhibits tensile strength of 700MPa, two times higher than that of monolithic Al2024, and around 4% elongation to failure. During plastic deformation, restricted dislocation activities and the accumulated dislocation at between FLGs may contribute to strengthening of Al2024/FLG composites.
Strengthening behavior of composite containing discontinuous reinforcement is strongly related with load transfer at the reinforcement–matrix interface. We selected multi-walled carbon nanotube ...(MWCNT) and few-layer graphene (FLG) as a reinforcing agent. By varying a volume fraction of the reinforcement, aluminum (Al) matrix composites were produced by a powder metallurgy method. Uniform dispersion and uniaxial alignment of MWCNT and FLG in the Al matrix are evidenced by high-resolution transmission electron microscope analysis. Although the reinforcements have a similar molecular structure, FLG has a 12.8 times larger specific surface area per volume more than MWCNT due to geometric difference. Therefore an increment of a yield stress versus a reinforcement volume fraction for FLG shows 3.5 times higher than that of MWCNT Consequently, for both reinforcements, the composite strength proportionally increases with the specific surface area on the composite, and the composites containing 0.7vol% FLG exhibit 440MPa of tensile strength.
This study evaluated the mechanical and thermal properties of aluminum alloy 2024 (Al2024) matrix composites reinforced with multi-walled carbon nanotube (MWCNT) or few-layered graphene (FLG) in the ...temperature range of 250–430 °C. The Al2024/MWCNT and Al2024/FLG composites were fabricated using powder metallurgy, and the associated microstructures were observed. At 350 °C, both composites maintain high yield stress about 110 MPa, since uniform dispersion of the nano-scale reinforcements has a strong interface, hinders the dislocation movement and eutectic phase coarsening and severe softening of the matrix. The composites also show a low thermal expansion coefficient of ∼18×10−6/K. The results are respectively over ∼2.5 times higher strength and ∼20% lower CTE than those of commercial Al alloy used as piston material (AlSi12CuMgNi).
BACKGROUND AND PURPOSE The transcriptional co‐activator with PDZ‐binding motif (TAZ) is characterized as a transcriptional modulator of mesenchymal stem cell differentiation into osteoblasts and ...adipocytes. Moreover, increased TAZ activity in the nucleus enhances osteoblast differentiation and suppresses adipocyte development by interacting with runt‐related transcription factor 2 (RUNX2) and PPARγ, respectively. Therefore, it would be of interest to identify low MW compounds that modulate nuclear TAZ activity.
EXPERIMENTAL APPROACH High‐throughput screening was performed using a library of low MW compounds in order to identify TAZ modulators that enhance nuclear TAZ localization. The effects and molecular mechanisms of a TAZ modulator have been characterized in osteoblast and adipocyte differentiation.
KEY RESULTS We identified 2‐butyl‐5‐methyl‐6‐(pyridine‐3‐yl)‐3‐2′‐(1H‐tetrazole‐5‐yl)‐biphenyl‐4‐ylmethyl‐3H‐imidazo4,5‐bpyridine (TM‐25659) as a TAZ modulator. TM‐25659 enhanced nuclear TAZ localization in a dose‐dependent manner and attenuated PPARγ‐mediated adipocyte differentiation by facilitating PPARγ suppression activity of TAZ. In addition, TAZ‐induced RUNX2 activity activation was further increased in osteoblasts, causing increased osteoblast differentiation. Accordingly, TM‐25659 suppressed bone loss in vivo and decreased weight gain in an obesity model. After oral administration, TM‐25659 had a favourable pharmacokinetic profile.
CONCLUSION AND IMPLICATIONS TM‐25659 stimulated nuclear TAZ localization and thus caused TAZ to suppress PPARγ‐dependent adipogenesis and enhance RUNX2‐induced osteoblast differentiation in vitro and in vivo. Our data suggest that TM‐25659 could be beneficial in the control of obesity and bone loss.
Patients who have residual invasive carcinoma after the receipt of neoadjuvant chemotherapy for human epidermal growth factor receptor 2 (HER2)-negative breast cancer have poor prognoses. The benefit ...of adjuvant chemotherapy in these patients remains unclear.
We randomly assigned 910 patients with HER2-negative residual invasive breast cancer after neoadjuvant chemotherapy (containing anthracycline, taxane, or both) to receive standard postsurgical treatment either with capecitabine or without (control). The primary end point was disease-free survival. Secondary end points included overall survival.
The result of the prespecified interim analysis met the primary end point, so this trial was terminated early. The final analysis showed that disease-free survival was longer in the capecitabine group than in the control group (74.1% vs. 67.6% of the patients were alive and free from recurrence or second cancer at 5 years; hazard ratio for recurrence, second cancer, or death, 0.70; 95% confidence interval CI, 0.53 to 0.92; P=0.01). Overall survival was longer in the capecitabine group than in the control group (89.2% vs. 83.6% of the patients were alive at 5 years; hazard ratio for death, 0.59; 95% CI, 0.39 to 0.90; P=0.01). Among patients with triple-negative disease, the rate of disease-free survival was 69.8% in the capecitabine group versus 56.1% in the control group (hazard ratio for recurrence, second cancer, or death, 0.58; 95% CI, 0.39 to 0.87), and the overall survival rate was 78.8% versus 70.3% (hazard ratio for death, 0.52; 95% CI, 0.30 to 0.90). The hand-foot syndrome, the most common adverse reaction to capecitabine, occurred in 73.4% of the patients in the capecitabine group.
After standard neoadjuvant chemotherapy containing anthracycline, taxane, or both, the addition of adjuvant capecitabine therapy was safe and effective in prolonging disease-free survival and overall survival among patients with HER2-negative breast cancer who had residual invasive disease on pathological testing. (Funded by the Advanced Clinical Research Organization and the Japan Breast Cancer Research Group; CREATE-X UMIN Clinical Trials Registry number, UMIN000000843 .).
Background
Bacterial flagellin, a Toll‐like receptor 5 agonist, is used as an adjuvant for immunomodulation. In this study, we aimed to evaluate the effect and its mechanism following intralymphatic ...administration of OVA‐flagellin (FlaB) mixture in the mouse model of allergic rhinitis.
Materials and Methods
BALB/c mice were sensitized with OVA and treated with an OVA‐FlaB mixture via intranasal, sublingual, and intralymphatic routes to evaluate the effect of each treatment. Several parameters for allergic inflammation and its underlying mechanisms were then evaluated.
Results
Intralymphatic injection of the OVA‐FlaB mixture reduced symptom scores, eosinophil infiltration in the nasal mucosa, and total and OVA‐specific IgE levels more significantly than intranasal and sublingual administration. Systemic cytokine (IL‐4, IL‐5, IL‐6, IL‐17, and IFN‐γ) production and local cytokine (IL‐4 and IL‐5) production were also reduced significantly after intralymphatic injection with OVA‐FlaB. Double intralymphatic injection of the mixture was more effective than single injection. Moreover, the expression of innate cytokines such as IL‐25 and IL‐33 in nasal epithelial cells was reduced, and the expression of chemokines such as CCL24 (eotaxin‐2), CXCL1, and CXCL2 was decreased in the nasal mucosa, suggesting the underlying mechanism for intralymphatic administration of the OVA‐FlaB mixture.
Conclusion
Intralymphatic administration of an OVA‐FlaB mixture was more effective in alleviating allergic inflammation than intranasal and sublingual administration in a mouse model of allergic rhinitis. This effect may be attributed to the reduced expression of innate cytokines and chemokines. This treatment modality can be considered as a new therapeutic method and agent.
Background and purpose
We investigated the effect of celecoxib, a selective inhibitor of cyclo‐oxygenase 2, in patients with intracerebral hemorrhage (ICH).
Methods
We conducted a multicenter, ...randomized, controlled, and open with blinded end‐point trial of 44 Korean patients 18 years or older with ICH within 24 h of onset. The intervention group (n = 20) received celecoxib (400 mg twice a day) for 14 days. The control group (n = 24) received the standard medical treatment for ICH. The primary end‐point was the number of patients with a change in the volume of perihematomal edema (PHE) from the 1st to the 7th ± 1 day (cut‐off value, 20%).
Results
The time from onset to computed tomography scan slightly differed between groups (177 ± 160 min for control vs. 297 ± 305 min for the celecoxib group; P = 0.10). In the primary end‐point analysis using cut‐off values, there was a significant shift to reduced expansion of PHE in the celecoxib group (P = 0.005). With respect to the secondary end‐points, there was also a significant shift to reduced expansion of ICH in the celecoxib group (P = 0.046). In addition, the expansion rate of PHE at follow‐up tended to be higher in the control group than in the celecoxib group (90.6 ± 91.7% vs. 44.4 ± 64.9%; P = 0.058).
Conclusions
In our small, pilot trial, administration of celecoxib in the acute stage of ICH was associated with a smaller expansion of PHE than that observed in controls.
The anisotropic mechanical properties and formability of Al–Si–Mg–Cu-based alloy sheets were investigated by varying their recrystallized grain sizes. By adding Cr and Mn and controlling the ...homogenization heat treatment, the recrystallized sheets with average grain sizes of 85, 61, 54, and 26 μm were prepared. As the average grain sizes of the recrystallized sheets decreased from 85 to 26 μm, the yield strength (YS) increased from 69.5 to 86.4 MPa due to grain boundary and particle strengthening. At the same time, the elongation was improved because the reduction in the stress concentration delayed the formation of the large-scale necking. The anisotropy in YS and elongation significantly decreased because a large number of fine grains with various orientations operated similar slip systems in all directions. Furthermore, grain refinement can increase and decrease the plastic strain ratio (r‾) and planar anisotropy (Δr), respectively, due to the formation of random textures. A bending formability map was proposed, which showed the acceptable and non-acceptable bending regions based on the grain size and flanging radius. This study provided valuable insight regarding the effects of refining recrystallized grains on anisotropic mechanical properties and formability.
•Al–Si–Mg–Cu-based alloy sheets with different grain sizes in the range of 85 to 26 μm were prepared.•The tradeoff between the strength and elongation was overcome using the grain refinement.•The grain refinement reduced the anisotropy of the strength, elongation, and r-value, which can be explained by the formation of a random texture.•A bending formability map, which indicated acceptable and non-acceptable bending regions depending on the grain size and flanging radius, was proposed.
Nanocomposites reinforced with nano-scale reinforcements exhibit excellent mechanical properties with low volume fraction of the reinforcement. For instance, only an addition of 0.7 vol.% few-layer ...graphene (FLG) into the pure titanium shows strength of ~1.5 GPa, obviously much superior to that of the monolithic titanium. The strengthening efficiency of composites is determined by several factors such as reinforcement geometrical/spatial characteristics and interfacial features between the matrix and the reinforcement. For the metal-matrix nanocomposites (MMNCs), since the nano-scale reinforcement has significantly high specific surface area, interfacial feature is more important and has to be clearly evaluated in understanding property of MMNCs. Although many researchers suggested the theoretical work using continuum mechanics in order to estimate the mechanical properties of the metallic composites, a clear determination has yet not to be proven by systematic experimental works. Here, we provide a new model to predict strength and stiffness of MMNCs based on quantitative analysis of efficiency parameters in which interface feature is strongly emphasized. To validate the model, we select multi-walled carbon nanotube (MWCNT) and FLG for reinforcement, and titanium (Ti) and aluminum (Al) for the matrix to modify bonding strength and specific surface area in the MMNCs.
Bone and dentin share similar biochemical compositions and physiological properties. Dentin, a major tooth component, is formed by odontoblasts; in contrast, bone is produced by osteoblasts. Osterix ...(Osx), a zinc finger-containing transcription factor, has been identified as an essential regulator of osteoblast differentiation and bone formation. However, it has been difficult to establish whether Osx functions in odontoblast differentiation and dentin formation. To understand the role of Osx in dentin formation, we analyzed mice in which Osx was subjected to tissue-specific ablation under the control of either the Col1a1 or the OC promoter. Two independent Osx conditional knockout mice exhibited similar molar abnormalities. Although no phenotype was found in the crowns of these teeth, both mutant lines exhibited short molar roots due to impaired root elongation. Furthermore, the interradicular dentin in these mice showed severe hypoplastic features, which were likely caused by disruptions in odontoblast differentiation and dentin formation. These phenotypes were closely related to the temporospatial expression pattern of Osx during tooth development. These findings indicate that Osx is required for root formation by regulating odontoblast differentiation, maturation, and root elongation. Cumulatively, our data strongly indicate that Osx is a site-specific regulator in tooth root formation.
PDF
