V is the only element in the periodic table that forms a complete solid solution with Cr and thus is particularly important in alloying strategy to ductilize Cr. This study combines first-principles ...density functional theory calculations and experiments to investigate the phase stability and elastic properties of Cr-V binary alloys. The cluster expansion study reveals the formation of various ordered compounds at low temperatures that were not previously known. These compounds become unstable due to the configurational entropy of bcc solid solution as the temperature is increased. The elastic constants of ordered and disordered compounds are calculated at both T = 0 K and finite temperatures. The overall trends in elastic properties are in agreement with measurements using the resonant ultrasound spectroscopy method. The calculations predict that addition of V to Cr decreases both the bulk modulus and the shear modulus, and enhances the Poisson's ratio, in agreement with experiments. Decrease in the bulk modulus is correlated to decrease in the valence electron density and increase in the lattice constant. An enhanced Poisson's ratio for bcc Cr-V alloys (compared to pure Cr) is associated with an increased density of states at the Fermi level. Furthermore, the difference charge density in the bonding region in the (110) slip plane is highest for pure Cr and decreases gradually as V is added. The present calculation also predicts a negative Cauchy pressure for pure Cr, and it becomes positive upon alloying with V. The intrinsic ductilizing effect from V may contribute, at least partially, to the experimentally observed ductilizing phenomenon in the literature.
The experiment was conducted to determine the role of nuclear factor (erythroid-derived 2)-like factor 2 (NFE2L2, formerly Nrf2) antioxidant response element (ARE) pathway in protecting bovine ...mammary epithelial cells (BMEC) against H2O2-induced oxidative stress injury. An NFE2L2 small interfering RNA (siRNA) interference or a pCMV6-XL5-NFE2L2 plasmid fragment was transfected to independently downregulate or upregulate expression of NFE2L2. Isolated BMEC in triplicate were exposed to H2O2 (600 μM) for 6 h to induce oxidative stress before transient transfection with scrambled siRNA, NFE2L2-siRNA, pCMV6-XL5, and pCMV6-XL5-NFE2L2. Cell proliferation, apoptosis and necrosis rates, antioxidant enzyme activities, reactive oxygen species (ROS) and malondialdehyde (MDA) production, protein and mRNA expression of NFE2L2 and downstream target genes, and fluorescence activity of ARE were measured. The results revealed that compared with the control, BMEC transfected with NFE2L2-siRNA3 had proliferation rates that were 9 or 65% lower without or with H2O2, respectively. These cells also had apoptosis and necrosis rates that were 27 and 3.5 times greater with H2O2 compared with the control group, respectively. In contrast, transfected pCMV6-XL5-NFE2L2 had proliferation rates that were 64.3% greater or 17% lower without or with H2O2 compared with the control group, respectively. Apoptosis rates were 1.8 times lower with H2O2 compared with the control. In addition, compared with the control, production of ROS and MDA and activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), and glutathione-S-transferase (GST) increased markedly in cells transfected with pCMV6-XL5-NFE2L2 and without H2O2. However, compared with the control, production of ROS and MDA and activity of CAT and GSH-Px increased markedly, whereas activities of SOD and GST decreased in cells transfected with pCMV6-XL5-NFE2L2 and incubated with H2O2. Compared with the control, cells transfected with NFE2L2-siRNA3 with or without H2O2 had lower production of ROS and MDA and activity of SOD, CAT, GSH-Px, and GST. Cells transfected with pCMV6-XL5-NFE2L2 with or without H2O2 had markedly higher protein and mRNA expression of NFE2L2, heme oxygenase-1 (HMOX-1), NADH quinone oxidoreductase 1, glutamate cysteine ligase catalytic subunit, and glutamyl cystine ligase modulatory subunit compared with the control incubations. Cells transfected with NFE2L2-siRNA3 without or with H2O2 had markedly lower protein and mRNA expression of NFE2L2, HMOX-1, NADH quinone oxidoreductase 1, glutamyl cystine ligase modulatory subunit, and glutamate-cysteine ligase catalytic subunit compared with the control incubations. In addition, expression of HMOX-1 was 5.3-fold greater with H2O2 compared with the control. Overall, results indicate that NFE2L2 plays an important role in the NFE2L2-ARE pathway via the control of HMOX-1. The relevant mechanisms in vivo merit further study.
•An improved Consistent Particle Method is developed to reduce pressure fluctuation.•The pressure Poisson equation with a hybrid source term is proposed.•The performance of the proposed algorithm is ...validated by sloshing examples.•Sloshing with a constrained floating baffle is simulated using the present method.•Experimental studies are conducted to partially verify the numerical algorithm.
The recently developed Consistent Particle Method (CPM) is improved to eliminate pressure fluctuation such that fluid–structure interaction problems can be accurately simulated with a partitioned coupling procedure. The strategy of smoothing pressure is to combine a zero-density-variation condition and a velocity-divergence-free condition to enforce fluid incompressibility. The proposed algorithm is validated by hydrostatic and free-sloshing examples, which show better pressure results with less spurious fluctuations. Using the improved CPM, water sloshing with a constrained floating baffle (CFB) is successfully simulated. The effect of CFB in sloshing mitigation is investigated. Experimental studies are conducted to partially verify the numerical algorithm.
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•Novel method by Flash DSC to measure the delay time for crystallization is proposed.•Delay time for marginal Al-based metallic glasses are precisely determined.•Minor-alloying effect ...on delay time and glass formation ability are studied.
The delay time for primary crystallization plays an important role in the understanding of the transport and nucleation behaviors during crystallization in metallic glasses. In this work, a novel method via Flash DSC is demonstrated to measure the delay time for primary crystallization in Al-based metallic glasses. In a typical Al-based metallic glass of Al87Y7Fe6, the delay times were established corresponding to different temperatures. Transmission electron microscopy tests before and after delay time were conducted to further verify the validity of the measured delay time. The effect of a 1 at.% substitution by Cu on the delay time of Al88Y7Fe5 was investigated to determine the effect of minor alloying on the glass formation ability. The significant changes in the primary crystallization temperatures were demonstrated to be directly related to the corresponding changes in the delay time. The results indicate that minor alloying that is designed to increase the delay time is an effective strategy to enhance the glass formation ability.
The design approach and validation of a single phase senary refractory high entropy alloy (HEA) MoNbTaTiVW was presented in the present study. The design approach was to combine phase diagram ...inspection of available binary and ternary systems and Calculation of Phase Diagrams prediction. Experiments using X-ray diffraction and scanning electron microscopy techniques verified a single phase microstructure in body centred cubic lattice for MoNbTaTiVW. The observed elemental segregation agrees well with the solidification prediction using the Scheil model. The lattice constant, density and microhardness were measured to be 0.3216 nm, 4.954 GPa and 11.70 g cm
− 3
respectively. The atomic size difference, the Ω parameter, enthalpy of mixing and entropy of mixing for MoNbTaTiVW HEA are 3.1%, 11.1, − 3.4 kJ mol
− 1
and +13.39 J K
− 1
mol
− 1
respectively.
To develop a population pharmacokinetic (PK) model for bedaquiline (BDQ) to describe the concentration-time data from patients with multidrug-resistant TB (MDR-TB) in China.
A total of 306 PK ...observations from 69 patients were used in a non-linear, mixed-effects modelling (NONMEM) approach. BDQ PK can be adequately described by a three-compartment model with a transit absorption model. The impact of baseline covariates, including age, sex, height, weight, alanine aminotransferase (ALT), aspartate aminotransferase (AST), apolipoprotein (ALP), total bilirubin (TBIL), direct bilirubin (DBIL), creatinine (CR), potassium (K
), calcium (Ca
) and magnesium (Mg
) on the oral clearance (CL/F) of BDQ were investigated.
In final population PK model, no significant covariates were found in the population PK model for BDQ. The population PK parameter estimate values for oral clearance (CL/F); CL/F between central compartment and peripheral compartment (Q1/F, Q2/F); peripheral volume of distribution (Vp1/F, VP2/F) were respectively 1.50 L/h (95% CI 1.07-1.93), 2.54 L/h (95% CI 1.67-3.41), 1,250 L (95% CI 616.9-1883.1), 2.00 L/h (95% CI 1.10-2.90) and 4,960 L (95% CI 1647.6-8272.4). Inter-individual variability on CL/F was 65.0%.
This is the first study to establish a population PK model for BDQ in Chinese patients with MDR-TB. The final model adequately described the data and had good simulation characteristics. Despite some limitations, the final population PK model was stable with good accuracy of parameter estimation.
This work focused on the development of a hybrid organic-inorganic TiO2 nanocomposite, which demonstrates the first ever report on harmful volatile organic compound (VOC) sensing and photocatalytic ...degradation-H2 production. The sensing and photocatalytic properties are enhanced by the synergetic effects of well-structured TiO2 nanotubes, metal nanoparticles and reduced graphene oxide loading for enhanced light absorption and charge-transfer kinetics. Hybridization of a functionalized TiO2 nanocomposite with a polyvinylidene fluoride (PVDF) matrix induced strong cross-linking networks between the inorganic-organic components, which promote mechanical reinforcement-flexibility and highly porous asymmetric structures. The developed solution processable nanocomposite has immense potential to remedy the global environmental and energy issues by producing clean water/air and energy from organic compound waste.
In this Technical Note, a new material (i.e., Duxseal) with high damping ratio is introduced to the wave impeding block (WIB) as an active vibration isolating barrier in the free field. To evaluate ...the performance of the Duxseal-WIB (DXWIB), a set of field tests are performed at three test sites of Jinan-Qingdao high-speed railway of China subjected to a moving load at a high speed of 250 km/h. Accelerations in the X-, Y-, and Z-directions are monitored at multiple distances away from the track. Characteristics of ground vibrations in both time and frequency domains are analyzed using the test data. The effectiveness of DXWIB in reducing the level of ground vibration is discussed and demonstrated by comparing with the case with traditional WIB.
•A new barrier Duxseal-WIB is developed to apply to high speed railway.•Excellent isolation effectiveness of Duxseal-WIB is confirmed.•Difference of effectiveness between DXWIB and traditional WIB are compared.
Single‐ or multicolor‐encoded microspheres are created by confining water‐soluble CdTe nanocrystals with different sizes within hydrogel microspheres of N‐isopropylacrylamide and 4‐vinylpyridine ...copolymer based on the pH‐responsive swelling behavior of the gel (see Figure). The emission intensity level and color of the resulting fluorescent spheres can be manipulated simply by changing the concentrations of the different‐sized NCs and their molar ratios.
BACKGROUND AND PURPOSE While maintaining cardiac performance, chronic β‐adrenoceptor activation eventually exacerbates the progression of cardiac remodelling and failure. We examined the adverse ...signalling pathways mediated by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and reactive oxygen species (ROS) after chronic β2‐adrenoceptor activation.
EXPERIMENTAL APPROACH Mice with transgenic β2‐adrenoceptor overexpression (β2‐TG) and non‐transgenic littermates were either untreated or treated with an antioxidant (N‐acetylcysteine, NAC) or NADPH oxidase inhibitors (apocynin, diphenyliodonium). Levels of ROS, phosphorylated p38 mitogen‐activated protein kinase (MAPK), pro‐inflammatory cytokines and collagen content in the left ventricle (LV) and LV function were measured and compared.
KEY RESULTS β2‐TG mice showed increased ROS production, phosphorylation of p38 MAPK and heat shock protein 27 (HSP27), expression of pro‐inflammatory cytokines and collagen, and progressive ventricular dysfunction. β2‐adrenoceptor stimulation similarly increased ROS production and phosphorylation of p38 MAPK and HSP27 in cultured cardiomyocytes. Treatment with apocynin, diphenyliodonium or NAC reduced phosphorylation of p38 MAPK and HSP27 in both cultured cardiomyocytes and the LV of β2‐TG mice. NAC treatment (500 mg·kg−1·day−1) for 2 weeks eliminated the up‐regulated expression of pro‐inflammatory cytokines and collagen in the LV of β2‐TG mice. Chronic NAC treatment to β2‐TG mice from 7 to 10 months of age largely prevented progression of ventricular dilatation, preserved contractile function (fractional shortening 37 ± 5% vs. 25 ± 3%, ejection fraction 52 ± 5% vs. 32 ± 4%, both P < 0.05), reduced cardiac fibrosis and suppressed matrix metalloproteinase activity.
CONCLUSION AND IMPLICATIONS β2‐adrenoceptor stimulation provoked NADPH oxidase‐derived ROS production in the heart. Elevated ROS activated p38 MAPK and contributed significantly to cardiac inflammation, remodelling and failure.
LINKED ARTICLE This article is commented on by Di Lisa et al., pp. 1009–1011 of this issue. To view this commentary visit http://dx.doi.org/10.1111/j.1476‐5381.2010.01130.x
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