IL-33 ameliorates Alzheimer’s disease-like pathology and cognitive decline

Alzheimer’s disease (AD) is a devastating condition with no known effective treatment. AD is characterized by memory loss as well as impaired locomotor ability, reasoning, and judgment. Emerging evidence suggests that the innate immune response plays a major role in the pathogenesis of AD. In AD, the accumulation of β-amyloid (Aβ) in the brain perturbs physiological functions of the brain, including synaptic and neuronal dysfunction, microglial activation, and neuronal loss. Serum levels of soluble ST2 (sST2), a decoy receptor for interleukin (IL)-33, increase in patients with mild cognitive impairment, suggesting that impaired IL-33/ST2 signaling may contribute to the pathogenesis of AD. Therefore, we investigated the potential therapeutic role of IL-33 in AD, using transgenic mouse models. Here we report that IL-33 administration reverses synaptic plasticity impairment and memory deficits in APP/PS1 mice. IL-33 administration reduces soluble Aβ levels and amyloid plaque deposition by promoting the recruitment and Aβ phagocytic activity of microglia; this is mediated by ST2/p38 signaling activation. Furthermore, IL-33 injection modulates the innate immune response by polarizing microglia/macrophages toward an antiinflammatory phenotype and reducing the expression of proinflammatory genes, including IL-1β, IL-6, and NLRP3, in the cortices of APP/PS1 mice. Collectively, our results demonstrate a potential therapeutic role for IL-33 in AD

Morphological and bending properties of cross-laminated timber prototype manufactured with densified Paraserianthes falcataria

Densification is a modification process commonly used to modify the density and hence, properties improvement of low-density wood. Cross-laminated timber (CLT) manufactured from plantation tree has gained more interest recently but the potentiality of using densified fast-grown plantation wood, Batai (Paraserianthes falcataria) in the layering of CLT has yet to be discovered. This study aims to investigate the relationship between morphology of densified wood and bending performance of lab-scale prototype CLT manufactured from it. Laminas after conditioned were hot-pressed (105 oC, 6 MPa for 10 minutes) for two stages with venting (press released for 1 minute 40 seconds) in between before cooling to below 100oC to reduce immediate springback. Densified laminas with three different targeted thicknesses (8, 10, and 15) mm were produced before further manufactured into three-layer CLT (24, 30, and 45) mm thick panels. CLT 60 mm thick panels from three pieces of undensified (20 mm) laminas acts as control. Results show that area of pores morphologically had reduced significantly (average 6.59 µm2 ) for laminas densified to 8 mm. CLT 24 show significant improvement up to 696% (Modulus of Elasticity) and 48.8% (Modulus of Rupture) when the area of pores had reduced. Morphological of densified laminas correlates negatively with bending properties of CLT

Towards Accurate Guided Diffusion Sampling through Symplectic Adjoint Method

Training-free guided sampling in diffusion models leverages off-the-shelf pre-trained networks, such as an aesthetic evaluation model, to guide the generation process. Current training-free guided sampling algorithms obtain the guidance energy function based on a one-step estimate of the clean image. However, since the off-the-shelf pre-trained networks are trained on clean images, the one-step estimation procedure of the clean image may be inaccurate, especially in the early stages of the generation process in diffusion models. This causes the guidance in the early time steps to be inaccurate. To overcome this problem, we propose Symplectic Adjoint Guidance (SAG), which calculates the gradient guidance in two inner stages. Firstly, SAG estimates the clean image via $n$ function calls, where $n$ serves as a flexible hyperparameter that can be tailored to meet specific image quality requirements. Secondly, SAG uses the symplectic adjoint method to obtain the gradients accurately and efficiently in terms of the memory requirements. Extensive experiments demonstrate that SAG generates images with higher qualities compared to the baselines in both guided image and video generation tasks

Spin-to-Orbital Angular Momentum Conversion in Semiconductor Microcavities

We experimentally demonstrate a technique for the generation of optical beams carrying orbital angular momentum using a planar semiconductor microcavity. Despite being isotropic systems, the transverse electric - transverse magnetic (TE-TM) polarization splitting featured by semiconductor microcavities allows for the conversion of the circular polarization of an incoming laser beam into the orbital angular momentum of the transmitted light field. The process implies the formation of topological entities, a pair of optical half-vortices, in the intracavity field

Modelling upper respiratory viral load dynamics of SARS-CoV-2

Relationships between viral load, severity of illness, and transmissibility of virus, are fundamental to understanding pathogenesis and devising better therapeutic and prevention strategies for COVID-19. Here we present within-host modelling of viral load dynamics observed in the upper respiratory tract (URT), drawing upon 2172 serial measurements from 605 subjects, collected from 17 different studies. We developed a mechanistic model to describe viral load dynamics and host response, and contrast this with simpler mixed-effects regression analysis of peak viral load and its subsequent decline. We observed wide variation in URT viral load between individuals, over 5 orders of magnitude, at any given point in time since symptom onset. This variation was not explained by age, sex, or severity of illness, and these variables were not associated with the modelled early or late phases of immune-mediated control of viral load. We explored the application of the mechanistic model to identify measured immune responses associated with control of viral load. Neutralizing antibody correlated strongly with modelled immune-mediated control of viral load amongst subjects who produced neutralizing antibody. Our models can be used to identify host and viral factors which control URT viral load dynamics, informing future treatment and transmission blocking interventions