Failure mechanisms of a SiC particles 2024Al composite under dynamic loading

Dynamic mechanical response of a 20 vol% silicon carbide particles (SiCp) reinforced 2024 Al composite prepared by powder metallurgy techniques were studied with a split Hopkinson bar. The fracture mechanisms and the deformation microstructure were examined with Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM). The present results indicate that the composite has a strong SiC-Al interfacial bonding; failure of the material is mainly caused by fracture of SiC particles and tearing failure of the SiC-Al interface. This failure by interface tearing with adhesion of an aluminium layer on SiC particles on the fracture surfaces has not been reported in SiC particle-reinforced aluminium composites. High-resolution transmission electron microscopy studies showed that many of the SiC-Al interfaces have coincident site lattice structures, which are considered to make a significant contribution to the strong interfacial bonding

Molecular Dissection of Neuroligin 2 and Slitrk3 Reveals an Essential Framework for GABAergic Synapse Development

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record In the brain, many types of interneurons make functionally diverse inhibitory synapses onto principal neurons. Although numerous molecules have been identified to function in inhibitory synapse development, it remains unknown whether there is a unifying mechanism for development of diverse inhibitory synapses. Here we report a general molecular mechanism underlying hippocampal inhibitory synapse development. In developing neurons, the establishment of GABAergic transmission depends on Neuroligin 2 (NL2), a synaptic cell adhesion molecule (CAM). During maturation, inhibitory synapse development requires both NL2 and Slitrk3 (ST3), another CAM. Importantly, NL2 and ST3 interact with nanomolar affinity through their extracellular domains to synergistically promote synapse development. Selective perturbation of the NL2-ST3 interaction impairs inhibitory synapse development with consequent disruptions in hippocampal network activity and increased seizure susceptibility. Our findings reveal how unique postsynaptic CAMs work in concert to control synaptogenesis and establish a general framework for GABAergic synapse development. Li et al. report a hierarchical process mediated by Neuroligin 2 and Slitrk3 for GABAergic synapse development. Neuroligin 2 also interacts with Slitrk3 to regulate GABAergic synaptogenesis. Selective perturbation of this interaction decreases GABAergic synaptic transmission and impairs hippocampal network activities.NIH/NINDS Intramural Research ProgramNIH/NICHD Intramural Research ProgramNIH/NEI Intramural Research Progra

On unitary subsectors of polycritical gravities

We study higher-derivative gravity theories in arbitrary space-time dimension d with a cosmological constant at their maximally critical points where the masses of all linearized perturbations vanish. These theories have been conjectured to be dual to logarithmic conformal field theories in the (d-1)-dimensional boundary of an AdS solution. We determine the structure of the linearized perturbations and their boundary fall-off behaviour. The linearized modes exhibit the expected Jordan block structure and their inner products are shown to be those of a non-unitary theory. We demonstrate the existence of consistent unitary truncations of the polycritical gravity theory at the linearized level for odd rank.Comment: 22 pages. Added references, rephrased introduction slightly. Published versio

Platelet Microparticles Mediate Glomerular Endothelial Injury in Early Diabetic Nephropathy

Background Glomerular endothelium dysfunction, which plays a crucial role in the pathogenesis of early diabetic nephropathy, might be caused by circulating metabolic abnormalities. Platelet microparticles, extracellular vesicles released from activated platelets, have recently emerged as a novel regulator of vascular dysfunction. Methods We studied the effects of platelet microparticles on glomerular endothelial injury in early diabetic nephropathy in rats with streptozotocin-induced diabetes and primary rat glomerular endothelial cells. Isolated platelet microparticles were measured by flow cytometry. Results Plasma platelet microparticles were significantly increased in diabetic rats, an effect inhibited in aspirin-treated animals. In cultured glomerular endothelial cells, platelet microparticles induced production of reactive oxygen species, decreased nitric oxide levels, inhibited activities of endothelial nitric oxide synthase and SOD, increased permeability of the glomerular endothelium barrier, and reduced thickness of the endothelial surface layer. Conversely, inhibition of platelet microparticles in vivo by aspirin improved glomerular endothelial injury. Further analysis showed that platelet microparticles activated the mammalian target of rapamycin complex 1 (mTORC1) pathway in glomerular endothelial cells; inhibition of the mTORC1 pathway by rapamycin or raptor siRNA significantly protected against microparticle-induced glomerular endothelial injury in vivo and in vitro. Moreover, platelet microparticle–derived chemokine ligand 7 (CXCL7) contributed to glomerular endothelial injury, and antagonizing CXCL7 using CXCL7-neutralizing antibody or blocking CXCL7 receptors with a competitive inhibitor of CXCR1 and CXCR2 dramatically attenuated such injury. Conclusions These findings demonstrate a pathogenic role of platelet microparticles in glomerular endothelium dysfunction, and suggest a potential therapeutic target, CXCL7, for treatment of early diabetic nephropathy

An activity-based integrated land-use transport model for urban spatial distribution simulation

This research develops an activity-based integrated land use/transport interaction model based on the concepts – activities (mainly, households and employment activities), activity location and relocation for Chinese regions. It consists of a residential and employment location sub-model, a transport sub-model and an implicit real estate rent adjustment sub-model. The model is developed to model the urban activity distribution evolution, predict urban spatial development trends and examine various planning decision implications. It spatially distributes household and employment activity change of a study area by zone based on the current activity distribution, land use policies and the accessibilities of the zones. The model is subsequently calibrated to predict the distribution of households and employment activities in Beijing metropolitan area in 2025. Model results show that the resident and employment densities are still high in central Beijing in 2025, and most zones’ resident densities are higher than their employment densities. However, there is also significant population density increase along the 6th ring road, indicating the relocation trend of the residents and businesses to the outskirts. This is consistent with the government objectives to decentralize activities within the central urban area. The paper also suggests that the model should be used mainly in examining the possible differences arising from the adoption of different policies though predicting future of a city distribution proves feasible

Diet folate, DNA methylation and genetic polymorphisms of MTHFR C677T in association with the prognosis of esophageal squamous cell carcinoma

<p>Abstract</p> <p>Background</p> <p>Folic acid may affect the development of human cancers. However, few studies have evaluated the consumption of diet folate in the prognosis of patients with esophageal squamous cell carcinoma (ESCC).</p> <p>Methods</p> <p>One hundred and twenty five ESCC patients underwent esophagectomy between January 2005 and March 2006 in the Yangzhong People's Hospital were recruited and followed up. The effects of diet folate, aberrant DNA methylation of selected genes and methylenetetrahydrofolate reductase (<it>MTHFR</it>) C677T genetic polymorphisms on the prognosis of ESCC were evaluated by using Cox proportional hazard regression models.</p> <p>Results</p> <p>Our analysis showed an inverse association between diet folate intake and the risk of death after esophagectomy. The median survival time was 3.06 years for low or moderate folate consumption and over 4.59 years for high folate consumption. After adjusting for potential confounders, the hazard ratios (95% confidence interval) [HRs (95% CI)] were 0.72 (0.36-1.46) for moderate and 0.39 (0.20-0.78) for high folate intake, respectively (<it>P </it>for trend = 0.007). This preventive effect was more evident in patients carrying <it>MTHFR </it>677CC genotype. No significant relation was observed between aberrant DNA methylation of <it>P16</it>, <it>MGMT </it>and <it>hMLH1 </it>gene, as well as <it>MTHFR </it>C677T genetic polymorphisms and the prognosis of ESCC.</p> <p>Conclusions</p> <p>Our research indicated that diet folate intake may have benefits on the prognosis of ESCC after esophagectomy. From a practical viewpoint, the findings of our study help to establish practical intervention and surveillance strategies for managements of ESCC patients and can finally decrease the disease burden.</p

Associations of Type 2 Diabetes with Common Variants in PPARD and the Modifying Effect of Vitamin D among Middle-Aged and Elderly Chinese

BACKGROUND: Previous studies have identified that variants in peroxisome proliferator-activated receptor PPAR-δ (PPARD), a target gene of vitamin D, were significantly associated with fasting glucose and insulin sensitivity in European populations. This current study sought to determine (1) whether the genetic associations of PPARD variants with type 2 diabetes and its related traits could be replicated in Chinese Han population, and (2) whether the associations would be modified by the effect of vitamin D status. METHODS AND FINDINGS: We genotyped 9 tag single nucleotide polymorphisms (SNPs) that cover the gene of PPARD (rs2267664, rs6902123, rs3798343, rs2267665, rs2267668, rs2016520, rs2299869, rs1053049, and rs9658056) and tested their associations with type 2 diabetes risk and its related traits, including fasting glucose, insulin and HbA1c in 3,210 Chinese Hans. Among the 9 PPARD tag SNPs, rs6902123 was significantly associated with risk of type 2 diabetes (odds ratio 1.75 [95%CI 1.22-2.53]; P = 0.0025) and combined type 2 diabetes and impaired fasting glucose (IFG) (odds ratio 1.47 [95%CI 1.12-1.92]; P = 0.0054). The minor C allele of rs6902123 was associated with increased levels of fasting glucose (P = 0.0316) and HbA1c (P = 0.0180). In addition, we observed that vitamin D modified the effect of rs6902123 on HbA1c (P for interaction = 0.0347). CONCLUSIONS/SIGNIFICANCE: Our findings demonstrate that common variants in PPARD contribute to the risk of type 2 diabetes in Chinese Hans, and provided suggestive evidence of interaction between 25(OH)D levels and PPARD-rs6902123 on HbA1c