Background Asthma is a heterogeneous disease that is caused by the interaction of genetic susceptibility with environmental influences. Genome-wide association studies (GWASs) represent a powerful ...approach to investigate the association of DNA variants with disease susceptibility. To date, few GWASs for asthma have been reported. Objectives A GWAS was performed on a population of patients with severe or difficult-to-treat asthma to identify genes that are involved in the pathogenesis of asthma. Methods A total of 292,443 single nucleotide polymorphisms (SNPs) were tested for association with asthma in 473 The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) cases and 1892 Illumina general population controls. Asthma-related quantitative traits (total serum IgE, FEV1 , forced vital capacity, and FEV1 /forced vital capacity) were also tested in identified candidate regions in 473 TENOR cases and 363 phenotyped controls without a history of asthma to analyze GWAS results further. Imputation was performed in identified candidate regions for analysis with denser SNP coverage. Results Multiple SNPs in the RAD50-IL13 region on chromosome 5q31.1 were associated with asthma: rs2244012 in intron 2 of RAD50 ( P = 3.04E-07). The HLA-DR/DQ region on chromosome 6p21.3 was also associated with asthma: rs1063355 in the 3′ untranslated region of HLA-DQB1 ( P = 9.55E-06). Imputation identified several significant SNPs in the TH 2 locus control region 3′ of RAD50 . Imputation also identified a more significant SNP, rs3998159 ( P = 1.45E-06), between HLA-DQB1 and HLA-DQA2. Conclusion This GWAS confirmed the important role of TH 2 cytokine and antigen presentation genes in asthma at a genome-wide level and the importance of additional investigation of these 2 regions to delineate their structural complexity and biologic function in the development of asthma.
Computational particle fluid dynamics method is utilized to study the influence of polydisperse and monodisperse particle size distribution, fuel addition, and biomass mixing ratio on the gas-solid ...flow behavior in a pilot-scale circulating fluidized bed (CFB). Numerical results show that a polydisperse system with different particle sizes can enhance the fluidization quality and the uniformity of the particle volume fraction in comparison with a monodisperse system with uniform particle sizes. When fuel is present in the CFB, the disturbance at the circulation inlet is eliminated and the particle aggregation effect at the wall is reduced. Furthermore, the particle volume fraction, pressure, and particle velocity distributions change only slightly as the biomass increased from 0% to 20% or from 50% to 100% of the total fuel mass. However, as the biomass ratio increases from 20% to 50%, the pressure drop in the riser decreases and the back-mixing degree at the riser wall weakens.
Macrophages activated by the Gram-negative bacterial product lipopolysaccharide switch their core metabolism from oxidative phosphorylation to glycolysis. Here we show that inhibition of glycolysis ...with 2-deoxyglucose suppresses lipopolysaccharide-induced interleukin-1β but not tumour-necrosis factor-α in mouse macrophages. A comprehensive metabolic map of lipopolysaccharide-activated macrophages shows upregulation of glycolytic and downregulation of mitochondrial genes, which correlates directly with the expression profiles of altered metabolites. Lipopolysaccharide strongly increases the levels of the tricarboxylic-acid cycle intermediate succinate. Glutamine-dependent anerplerosis is the principal source of succinate, although the 'GABA (γ-aminobutyric acid) shunt' pathway also has a role. Lipopolysaccharide-induced succinate stabilizes hypoxia-inducible factor-1α, an effect that is inhibited by 2-deoxyglucose, with interleukin-1β as an important target. Lipopolysaccharide also increases succinylation of several proteins. We therefore identify succinate as a metabolite in innate immune signalling, which enhances interleukin-1β production during inflammation.
•The addition of V promotes the phase transition proceeding of Ni-rich NiTi alloys.•Mechanical properties change with the change of V content.•A small amount of V addition helps to improve the ...oxidation resistance.•The addition of 3 at% V is most effective for improvements.
Highly Ni-rich NiTi alloys have attracted increasing attention as new candidates for bearing materials owing to their high hardness, low density, good corrosion resistance, and good dimensional stability. The main phases of the Ni55Ti45 (at%) (60NiTi) alloy consist of B2-NiTi matrix, equilibrium Ni3Ti, metastable Ni4Ti3 and Ni3Ti2, and a small amount of Ti2Ni phase. The ultra-high hardness of 60NiTi was attributed to the high volume fraction of nanoscale Ni4Ti3 phase and significant internal strain resulted from its coherence with the NiTi matrix. In this study, a series of 60NiTi-V alloys were prepared to study the effect of V addition on the microstructure, mechanical properties and oxidation performance of 60NiTi. The additional V enhanced the transformation from Ni4Ti3 phase to Ni3Ti2 and Ni3Ti phases. When the V content exceeded 3 at%, a grid-like Ni3Ti2 phase was formed in the alloy, and when the V content reached 10 at%, the formation of Ni3Ti phase was promoted. Moreover, the morphology and distribution of Ni3Ti2 phase changed with changing V content. The hardness of the alloy increased with increasing V content, whereas the fracture toughness and tensile strength increased at first and then decreased, owing to the solid solution strengthening effect of V and strengthening effect of Ni3Ti2 phase. At 500 °C, the oxidation resistance of 60NiTi-V alloys with V contents of less than 3 at% V was higher than that of binary 60NiTi. Conversely, the oxidation of the 60NiTi-V alloy with a V content of 3 at% was more severe than that of binary 60NiTi at a high oxidation temperature of 800 °C, because V promoted outward Ni diffusion. Therefore, a V content of less than 3 at% was effective for improving the microstructure and properties of highly Ni-rich NiTi alloys; moreover, in this study, we provided a new idea for strengthening highly Ni-rich NiTi alloys and expanding their applications.
Wirelessly actuated soft smart materials have great potential applications in real-world actuation and sensing in robotics and biomedical engineering. On the other hand, layered structures can gain ...more versatile and functional properties then conventional structures. This paper studies the photo- and magneto-responses of a layered beam consisting of liquid crystal elastomers and magnetic responsive elastomers. Based on the finite deformation theory and taking into account the coupling effect of light incidence angle and deformation, governing equation of the layered beam is derived and solved by a new numerical mothed. The results are validated by previous experimental data. It is found that the coupling effect of light incidence angle and the deformation of beam should be taken into account, especially for soft materials with large deformation. For example, neglecting the coupling effect of the light incidence angle and deformation, the maximum deflection of the cantilever beam will be underdetermined by 20.5%, if the light intensity reaches at 1.2 kW/m
2
. Whether the coupling effect of the light incidence angle and deformation enhances or reduces bending deformation of the beam depends on its boundary conditions and the initial light incidence angle. These results may be useful for designing photo- and magneto-responsive soft robotic and other functional devices.
This study aimed to assess preoperative radiological and clinical examinations for identifying bone status and to evaluate survival outcomes in patients undergoing marginal mandibulectomy for the ...primary treatment of oral squamous cell carcinoma. The medical records, enhanced computed tomography (CT) scans, and pathological specimens of these patients were reviewed. Disease-free (DFS), local recurrence-free (LRFS), and osteoradionecrosis-free (ORNFS) survival were analysed. The study included 104 patients. The preoperative CT and clinical examinations achieved a sensitivity of 45.8% and specificity of 100% for judging bone condition. LRFS was 79.6% and DFS was 68.8%. Pathological bone invasion in significantly affected DFS (P = 0.597), while DFS was significantly higher for those with a lower clinical tumour stage (1/2 vs 3/4; P = 0.005) and postoperative radiotherapy (P = 0.011). Among 39 patients receiving postoperative radiotherapy, ORNFS was 75.2%. Postoperative chemotherapy significantly decreased ORNFS (P = 0.009). Tumour subsite (P = 0.003) and the resection site (P = 0.035) significantly affected the remaining bone height. The results indicate that CT and clinical examinations cannot precisely identify superficial bone damage, but work well in selecting patients for marginal resection. Adhering to current indications, this resection approach can guarantee safe bone margins in terms of survival outcomes.
Damping ratio is the main parameter representing the property of materials in vibration reduction. In this study, simply supported beams were tested using a free vibration method to determine the ...relationships between damping ratio in small deformation and the size as well as amount of rubber particles in rubberized concrete. Elastic wave method and beam element method were used to test the dynamic modulus of rubberized concrete. A comparison between the static modulus and the dynamic modulus was also conducted. It was observed that the damping ratios of rubberized concrete improved considerably compared to those of normal concrete. The dynamic modulus elasticity of rubberized concrete was lower than that of normal concrete. The crushed rubberized concrete had better damping properties but lower dynamic and static modulus of elasticity than ground rubberized concrete. The results of the study provide valuable information for a better understanding of dynamic properties of rubberized concrete.
The microstructure evolution, hardness, compressive and tensile properties of 60NiTi alloy closely related to aging temperature and aging time are systematically characterized. Different phase ...compositions are achieved through aging in the temperature range of 400 °C–1000 °C for various times. The experimental results show that the variation in ductility and strength strongly depends on the microstructure. In tensile tests, a high volume fraction Ni4Ti3 phase precipitated after aging at 400 °C, 500 °C and 900 °C, resulting in high tensile strength and low elongation. The 60NiTi alloy fractured in brittle mode. The precipitations of the alloys which aged at 600 °C for 12 h and 700 °C for 3 h, 6 h, and 12 h are Ni3Ti2 and Ni3Ti phases. Alloys with Ni3Ti2 and Ni3Ti showed plastic deformation during tensile testing. The fracture surface morphology after tensile testing was characterized by SEM, and the microstructure of the samples after deformation was analyzed with TEM. It was found that the active dislocations in the matrix cut through the Ni3Ti2 and Ni3Ti phases, which resulted in plastic deformation. The relationship between the microstructure and mechanical properties of 60NiTi alloy is discussed in the pursuit of the ideal structure.
◆Alloys with Ni4Ti3 phase show high hardness and strength.◆Alloys with Ni3Ti2 and Ni3Ti phase have a plastic deformation.◆Different phases precipitate after aging from 400 °C to 1000 °C at various times.◆The active dislocations in the matrix cut through the Ni3Ti2 and Ni3Ti phases.
Abstract Parkinson's disease (PD) is a progressive neurological disorder that is often associated with various gastrointestinal (GI) symptoms. The link between the alteration of dopaminergic system ...and the symptoms of the GI tract in PD is complicated. To determine the changes in the dopaminergic system in the GI tract in PD, two kinds of rodent PD models were used in the present study. One was 6-hydroxydopamine (6-OHDA) -treated rats in which 6-OHDA was microinjected in the bilateral substantia nigra (SN). The other was 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) -treated mice in which MPTP was injected intraperitoneally. Immunofluorescence, reverse transcription (RT)-real time polymerase chain reaction (PCR) and Western blot were used to evaluate and compare the levels of mRNA and protein expression of tyrosine hydroxylase (TH) and dopamine transporter (DAT) in the GI tract between normal and rodent PD models, as well as between 6-OHDA-treated rats and MPTP-treated mice. The results indicated that TH- and DAT-positive cells were widely distributed in the GI tract. There were significant differences in TH and DAT expression in the GI tract between normal and PD models, as well as between 6-OHDA-treated rats and MPTP-treated mice. The protein levels of TH and DAT in the GI tract were significantly increased in 6-OHDA-treated rats, but the protein level of TH was significantly decreased in MPTP-treated mice. In addition, there was visible atrophy of gastric epithelial parietal cells in MPTP-treated mice, although the protein level of DAT was not significantly changed. The different alterations of dopaminergic system in the GI tract of the two kinds of PD models might underline the differences in GI symptoms in PD patients and might be correlated with the disease severity and disease process affecting the GI tract.
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