Nearly 100% selective and visible-light-driven methane conversion to formaldehyde via. single-atom Cu and Wδ+

Direct solar-driven methane (CH4) reforming is highly desirable but challenging, particularly to achieve a value-added product with high selectivity. Here, we identify a synergistic ensemble effect of atomically dispersed copper (Cu) species and partially reduced tungsten (Wδ+), stabilised over an oxygen-vacancy-rich WO3, which enables exceptional photocatalytic CH4 conversion to formaldehyde (HCHO) under visible light, leading to nearly 100% selectivity, a very high yield of 4979.0 μmol·g-1 within 2 h, and the normalised mass activity of 8.5 × 106 μmol·g-1Cu·h-1 of HCHO at ambient temperature. In-situ EPR and XPS analyses indicate that the Cu species serve as the electron acceptor, promoting the photo-induced electron transfer from the conduction band to O2, generating reactive •OOH radicals. In parallel, the adjacent Wδ+ species act as the hole acceptor and the preferred adsorption and activation site of H2O to produce hydroxyl radicals (•OH), and thus activate CH4 to methyl radicals (•CH3). The synergy of the adjacent dual active sites boosts the overall efficiency and selectivity of the conversion process

GluN2A NMDA Receptor Enhancement Improves Brain Oscillations, Synchrony, and Cognitive Functions in Dravet Syndrome and Alzheimer's Disease Models.

NMDA receptors (NMDARs) play subunit-specific roles in synaptic function and are implicated in neuropsychiatric and neurodegenerative disorders. However, the in vivo consequences and therapeutic potential of pharmacologically enhancing NMDAR function via allosteric modulation are largely unknown. We examine the in vivo effects of GNE-0723, a positive allosteric modulator of GluN2A-subunit-containing NMDARs, on brain network and cognitive functions in mouse models of Dravet syndrome (DS) and Alzheimer's disease (AD). GNE-0723 use dependently potentiates synaptic NMDA receptor currents and reduces brain oscillation power with a predominant effect on low-frequency (12-20 Hz) oscillations. Interestingly, DS and AD mouse models display aberrant low-frequency oscillatory power that is tightly correlated with network hypersynchrony. GNE-0723 treatment reduces aberrant low-frequency oscillations and epileptiform discharges and improves cognitive functions in DS and AD mouse models. GluN2A-subunit-containing NMDAR enhancers may have therapeutic benefits in brain disorders with network hypersynchrony and cognitive impairments

α-Melanocyte Stimulating Hormone Prevents GABAergic Loss and Improves Cognitive Function in Alzheimer's Disease

In Alzheimer's disease (AD), the appropriate excitatory/inhibitory balance required for memory formation is impaired. In order to elucidate deficits in the inhibitory gamma-aminobutyric acid (GABA)-ergic system in AD and to establish a link between GABAergic dysfunction and cognition, the TgCRND8 mouse model of AD was utilized. TgCRND8 mice with established amyloid beta peptide (Abeta) pathology exhibit spatial memory deficits and altered anxiety. Concomitant with behavioural changes, GABAergic deficits are observed in the hippocampus. The GABAergic marker glutamic acid decarboxylase 67 (GAD67) mRNA and protein levels in the hippocampus as well as the number of GAD67+ GABAergic cells in the CA1 region of the hippocampus are significantly decreased. However, at this stage of Abeta pathology, the number of ChAT+ cholinergic cells in the septum remains unchanged, suggesting that cholinergic cells may not underlie behavioural deficits. The GABAergic loss may represent an early target in AD disease progression. By increasing inhibition, the physiological excitatory/inhibitory balance in the brain may be restored resulting in normal function. I found that the neuropeptide, alpha-melanocyte stimulating hormone (alpha-MSH), prevents the loss of GAD67 mRNA, protein levels and GAD67+ cells in the CA1 region of the hippocampus. In particular, alpha-MSH protects the loss of the somatostatin (SST) expressing subtype of GAD67+ inhibitory interneurons. SST is reduced in the CSF and brain of AD patients and SST levels are correlated with cognitive function. By preserving hippocampal GAD67+ cells, especially the SST+ subtype, alpha-MSH improved spatial memory in TgCRND8 mice and prevented changes in anxiety independent of altering Abeta; peptide load in the brain. alpha-MSH modulated the excitatory/inhibitory balance in the brain by restoring GABAergic inhibition and as a result, improved cognition in TgCRND8 mice.Ph.D.2016-11-30 00:00:0

Region-specific Distribution of β-Amyloid and Cytokine Expression in TgCRND8 Mice

Alzheimer’s disease (AD) is a multifactorial disease that results in progressive neurodegeneration. Brain regions are differentially affected in AD; some are more vulnerable to degeneration than others. There is an age-dependent effect on beta-amyloid (Aβ) accumulation and neuroinflammation as disease progresses. In the TgCRND8 APP transgenic mouse model, levels of various Aβ species and cytokines were determined as a function of brain region and age. Aβ was found to accumulate in the brain prior to the sequential elevation of IL-1β and CXCL1. Levels of Aβ, IL-1β and CXCL1 were elevated in regions that are severely affected in AD patients. It has been shown for the first time in an APP transgenic model that CXCL1 elevation occurs following IL-1β elevation.MAS

Raid the Chat Room: The Effects of Group Size on User Engagement in Online Synchronized Communication

Online synchronous platforms, such as live streaming, spend tremendous efforts engaging users in a real-time setting, which has gained considerable popularity very recently. While the existing literature finds that the group size of peers positively affects user engagement on asynchronous platforms, the effect of group size remains unexplored in the context of synchronous streaming. In this work, we leverage the unique raid functionality, an exogenous increase in live streaming viewers, and empirically examine how group size affects users’ real-time commenting engagement. Collecting and analyzing chat history in 13,382 playbacks on Twitch, our result suggests that existing viewers (users who engage in the live streaming channel before the raid) tend to engage less after the raid. The findings in this paper indicate a negative effect of group size on viewer engagement in the synchronous communication setting, which theoretically extends the prior literature in user engagement and crowd effects

Blade Shape Optimization and Analysis of a Propeller for VTOL Based on an Inverse Method

With the rapid development of vertical takeoff and landing (VTOL) aircraft, the blade design of a propeller suitable for VTOL aircraft with a wide range of operating conditions has become a challenging and popular task. This paper proposes a multi-objective optimization framework for a VTOL propeller using an inverse design method at the cruising stage, which is developed from the Betz optimum theory and blade element momentum theory (BEMT). Different from passing studies, the maximum thrust-to-weight ratio at hover (MTWRH) is taken as one of the two objectives in this paper, which is closely related to the wind-resistance capability and maneuverability during takeoff and landing. The other objective is the energy consumption of the whole mission profile. A fixed pitch propeller (FPP) and a variable pitch propeller (VPP) are both optimized using the proposed framework for the Vahana A3 tilt-wing aircraft and validated by the computational fluid dynamics (CFD) method. The influences of the level flight energy ratio, hover disk loading and cruising speed toward the optimization result are analyzed, respectively. The results show that the MTWRH has a significant impact on the optimization result both for the FPP and VPP. A comparison between the two propeller forms validates the advantages of the VPP both in energy saving and takeoff maneuverability. The quantitative rules of this advantage with the level flight energy ratio are calculated to provide a reference for choosing the appropriate form. Overall, the methodology and general rules presented in this paper support the propeller optimization and form selection for VTOL aircraft

The expression of apoptosis inducing factor (AIF) is associated with aging-related cell death in the cortex but not in the hippocampus in the TgCRND8 mouse model of Alzheimer’s disease

Abstract Background Recent evidence has suggested that Alzheimer’s disease (AD)-associated neuronal loss may occur via the caspase-independent route of programmed cell death (PCD) in addition to caspase-dependent mechanisms. However, the brain region specificity of caspase-independent PCD in AD-associated neurodegeneration is unknown. We therefore used the transgenic CRND8 (TgCRND8) AD mouse model to explore whether the apoptosis inducing factor (AIF), a key mediator of caspase-independent PCD, contributes to cell loss in selected brain regions in the course of aging. Results Increased expression of truncated AIF (tAIF), which is directly responsible for cell death induction, was observed at both 4- and 6-months of age in the cortex. Concomitant with the up-regulation of tAIF was an increase in the nuclear translocation of this protein. Heightened tAIF expression or translocation was not observed in the hippocampus or cerebellum, which were used as AD-vulnerable and relatively AD-spared regions, respectively. The cortical alterations in tAIF levels were accompanied by increased Bax expression and mitochondrial translocation. This effect was preceded by a significant reduction in ATP content and an increase in reactive oxygen species (ROS) production, detectable at 2 months of age despite negligible amounts of amyloid-beta peptides (Aβ). Conclusions Taken together, these data suggest that AIF is likely to play a region-specific role in AD-related caspase-independent PCD, which is consistent with aging-associated mitochondrial impairment and oxidative stress

Nav1.1-Overexpressing Interneuron Transplants Restore Brain Rhythms and Cognition in a Mouse Model of Alzheimer’s Disease

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Amyloid-β-dependent compromise of microvascular structure and function in a model of Alzheimer's disease

The majority of patients with Alzheimer’s disease have cerebral amyloid angiopathy, thus showing deposition of amyloid-β peptides in the walls of leptomeningeal and cortical arterioles. These deposits are believed to result from impaired clearance of parenchymal amyloid-β peptides. In the current work, we examined the changes in cortical microvascular structure and function in situ in TgCRND8, a transgenic mouse model of Alzheimer’s disease. In contrast to venules, cortical arterioles were shown to increase in tortuosity and decrease in calibre with amyloid-β peptide accumulation. These structural changes were accompanied by progressive functional compromise, reflected in higher dispersion of microvascular network transit times, elongation of the transit times, and impaired microvascular reactivity to hypercapnia in the transgenic mice. Moreover, inhibition of amyloid-β peptide oligomerization and fibrillization via post-weaning administration of scyllo-inositol, a naturally occurring stereoisomer of myo-inositol, rescued both structural and functional impairment of the cortical microvasculature in this Alzheimer’s disease model. These results demonstrate that microvascular impairment is directly correlated with amyloid-β accumulation and highlight the importance of targeting cerebrovascular amyloid angiopathy clearance for effective diagnosis, monitoring of disease progression and treatment of Alzheimer’s disease