Increased Orexin Expression Promotes Sleep/Wake Disturbances in the SOD1-G93A Mouse Model of Amyotrophic Lateral Sclerosis

Background：Sleep/wake disturbances in patients with amyotrophic lateral sclerosis （ALS） are well-documented,however,no animal or mechanistic studies on these disturbances exist.Orexin is a crucial neurotransmitter in promoting wakefulness in sleep/wake regulation,and may play an important role in sleep disturbances in ALS.In this study,we used SOD1-G93A transgenic mice as an ALS mouse model to investigate the sleep/wake disturbances and their possible mechanisms in ALS.Methods：Electroencephalogram/electromyogram recordings were performed in SOD1-G93A transgenic mice and their littermate control mice at the ages of 90 and 120 days,and the samples obtained from these groups were subjected to quantitative reverse transcriptase-polymerase chain reaction,western blotting,and enzyme-linked immunosorbent assay.Results：For the first time in SOD1-G93A transgenic mice,we observed significantly increased wakefulness,reduced sleep time,and up-regulated orexins （prepro-orexin,orexin A and B） at both 90 and 120 days.Correlation analysis confirmed moderate to high correlations between sleep/wake time （total sleep time,wakefulness time,rapid eye movement [REM] sleep time,non-REM sleep time,and deep sleep time） and increase in orexins （prepro-orexin,orexin A and B）.Conclusion：Sleep/wake disturbances occur before disease onset in this ALS mouse model.Increased orexins may promote wakefulness and result in these disturbances before and after disease onset,thus making them potential therapeutic targets for amelioration of sleep disturbances in ALS.Further studies are required to elucidate the underlying mechanisms in the future.

A note on the numerical simulations of flow past a wavy square-section cylinder

The flow past a square-section cylinder with a geometric disturbance is investigated by numerical simulations. The extra terms, due to the introduction of mapping transformation simulating the effect of disturbance into the transformed Navier-Stokes equations, are correctly derived, and the incorrect ones in the previous literature are pointed out and analyzed. Furthermore, the relationship between the vorticity, especially on the cylinder surface, and the disturbance is derived and explained theoretically. The computations are performed at two Reynolds numbers of 100 and 180 and three amplitudes of waviness of 0.006, 0.025 and 0.167 with another aim to explore the effects of different Reynolds numbers and disturbance on the vortex dynamics in the wake and forces on the body. Numerical results have shown that, at the mild waviness of 0.025, the Kairmain vortex shedding is suppressed completely for Re = 100, while the forced vortex dislocation is appeared in the near wake at the Reynolds number of 180. The drag reduction is up to 21.6% at Re = 100 and 25.7% at Re = 180 for the high waviness of 0.167 compared with the non-wavy cylinder. The lift and the Strouhal number varied with different Reynolds numbers and the wave steepness are also obtained.

High fidelity numerical simulations on the unsteady flow field of low-pressure turbine cascades with and without upstream disturbance at moderate Reynolds number

This paper numerically investigates the aerodynamic performance of the T106A low-pressure turbine based with different inflow conditions at moderate Reynolds number by using high performance computing based on high order unstructured methods.Two different inflow conditions respectively of uniform and disturbed are considered,while for the latter a small circular cylinder is placed upstream of the cascade to generate wake turbulence as a long-standing disturbance.A high order Fourier-spectral/hp element method is employed to solve the flow dynamics in the cascade of high complex geometries.Flow transition characteristics are quantified in terms of the distribution of cascade wall surface pressure and friction coefficient,the distribution of wake profile pressure loss and the evolution characteristics of boundary layer flow structures as well.The numerical results show that the current numerical simulations accurately predict the flow transition performance of low-pressure turbine cascades and capture the effects of wake-generated disturbance on the cascade,which is shown to effectively modify the flow transition performance as compared with the uniform inflow case.