Induced Pluripotent Stem Cell-Derived Human Glutamatergic Neurons as a Platform for Mechanistic Assessment of Inducible Excitotoxicity in Drug Discovery

Since the guiding principles of Replace, Reduce, and Refine were published, wider context-of-use for alternatives to animal testing have emerged. Induced pluripotent stem cell-derived human glutamatergic-enriched cortical neurons can be leveraged as 2- and 3-dimensional platforms to enable candidate drug screening. Uniquely so, 2-dimensional models are useful considering that they exhibit spontaneous firing, while, 3-dimensional models show spontaneous synchronized calcium transient oscillations. Here, the limitations of selected induced acute seizure models as well as the early utilization of fully differentiated glutamatergic neuron models for interrogation of inducible excitotoxicity following exposure to neuromodulators will be described. The context of use for candidate biomarkers of inducible seizure is also discussed

The Analysis of Spatial Pattern and Hotspots of Aviation Accident and Ranking the Potential Risk Airports Based on GIS Platform

Aviation accident analysis is an important task to ensure aviation safety. The existing researches mainly focus on the analysis of aviation accident time characteristics and accident causes and less analysis of the spatial characteristics of aviation accidents. The spatial characteristics analysis of aviation accidents can identify hot spots of aviation accidents, improve the accuracy of aviation accident emergency management, and provide decision support for airport route planning. This study established the severity index of aviation accident based on aviation accident data, using GIS spatial analysis methods to study the spatial distribution characteristics of aviation accidents. The hot spots were identified in the aviation accidents. Finally, airports around the accident hot spots were ranked to obtain the airports with high potential aviation risks based on RI, taking Florida as an example. It was found that in the Florida aviation accident, general aviation accidents accounted for the majority, but the aviation accident severity index for air route flight was far greater than general aviation accidents. From the spatial distribution point of view, accidents with high severity index were distributed around large international airports. The Density Center for Aviation Accidents was located in Tampa, Miami, and some airports link areas in Florida. In terms of the Moran’s I index, the distribution of aviation accidents tended to aggregate in the region as a whole. However, aviation accident severity index was randomly distributed for each year separately. At the level of significance of 0.01, there were a total of 75 accident hotspots in the Florida region, mainly in the north and southwest. Airports with high RI in the Florida area were mainly concentrated in the Miami area and the Tampa Bay area, and Orlando Airport was ranked outside the top 10. Document type: Articl

Interleukin-6 gene -572G/C polymorphism and prostate cancer risk

Background: The aim of the present study was to determine whether the interleukin-6 (IL-6) -572G/C polymorphism correlates with prostate cancer.Methods: According to inclusion and exclusion criteria, the association of the IL-6 -572G/C polymorphism with prostate cancer was searched in databases and analyzed using comprehensive meta-analysis software. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the associations.Results: We considered a total of six case-control studies including 2237 patients and 1754 controls and the meta-analysis results showed significant association between the IL-6 -572G/C polymorphism and prostate cancer risk(CC vs GG: OR = 0.49, 95% CI =0.37-0.65;CG vs GG: OR =0.71, 95% CI = 0.58-0.87; the dominant model: OR =0.65, 95% CI = 0.54-0.79;the recessive model: OR =0.70, 95% CI = 0.58-0.85). In stratified analyses by ethnicity, significant associations were found among Asian populations. However, no significant association was found in Caucasian populations.Conclusion: Our findings demonstrated that the -572G/C polymorphism of the IL-6 gene may be a risk factor for the development of prostate cancer in Asians.Keywords: Prostate cancer, IL-6 polymorphisms, risk

Adaptive Sliding Mode Control of Permanent Magnet Direct-Drive Wind Turbine

The damping coefficient of permanent magnet direct-drive (PMDD) wind turbine is unmeasurable. To solve the problem, this paper attempts to design a sliding mode control (SMC) strategy that adapts to the speed of PMDD wind turbine. Firstly, the authors analyzed the features of wind turbines, and the nonlinear dynamic structural features of permanent magnet synchronous machine (PMSM). Next, the parameter adaptive law was designed based on Lyapunov stability theory, and backstepping control was combined with SMC into a comprehensive control strategy that regulates the speed of wind turbines. Simulation results show that the proposed strategy can compensate for the disturbance of uncertain parameters, and ensure the frequency stability of the wind turbine

Topological Corner States in Graphene by Bulk and Edge Engineering

Two-dimensional higher-order topology is usually studied in (nearly) particle-hole symmetric models, so that an edge gap can be opened within the bulk one. But more often deviates the edge anticrossing even into the bulk, where corner states are difficult to pinpoint. We address this problem in a graphene-based $\mathbb{Z}_2$ topological insulator with spin-orbit coupling and in-plane magnetization both originating from substrates through a Slater-Koster multi-orbital model. The gapless helical edge modes cross inside the bulk, where is also located the magnetization-induced edge gap. After demonstrating its second-order nontriviality in bulk topology by a series of evidence, we show that a difference in bulk-edge onsite energy can adiabatically tune the position of the crossing/anticrossing of the edge modes to be inside the bulk gap. This can help unambiguously identify two pairs of topological corner states with nonvanishing energy degeneracy for a rhombic flake. We further find that the obtuse-angle pair is more stable than the acute-angle one. These results not only suggest an accessible way to "find" topological corner states, but also provide a higher-order topological version of "bulk-boundary correspondence"

Electronic Structures of SiC Nanoribbons

Electronic structures of SiC nanoribbons have been studied by spin-polarized density functional calculations. The armchair nanoribbons are nonmagnetic semiconductor, while the zigzag nanoribbons are magnetic metal. The spin polarization in zigzag SiC nanoribbons is originated from the unpaired electrons localized on the ribbon edges. Interestingly, the zigzag nanoribbons narrower than $\sim$4 nm present half-metallic behavior. Without the aid of external field or chemical modification, the metal-free half-metallicity predicted for narrow SiC zigzag nanoribbons opens a facile way for nanomaterial spintronics applications.Comment: 10 pages, 5 figure