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The antihistamine astemizole has shown disease-modifying effects in several preclinical disease models of Parkinson's disease (PD). Astemizole also interacts with an anomalous aggregation of Alzheimer's disease-related amyloid-β (Aβ) peptide and has inhibitory activity on the human prion protein PrPSc. We hypothesized that the proposed preclinical benefits of astemizole on PD can be associated with the attenuation of pathological α-synuclein (α-syn) aggregation. We tested the effects of astemizole on the fibrillation processes of amyloid peptides using thioflavin T aggregation monitoring, Congo red spectral analysis, cell viability study, and transmission electron microscopic imaging. We found that astemizole did not inhibit α-syn aggregation in vitro even at a high molar ratio but inhibited the assembly of Aβ aggregates. Our results suggest that the inhibitory effect of astemizole on amyloid formation is target-protein selective, and the proposed beneficial effects of this compound observed in translational PD models might not be due to its ameliorating effects on α-syn aggregation. [ABSTRACT FROM AUTHOR]

In this study, we examined non-Oberbeck–Boussinesq (NOB) effects on a water-filled differentially heated vertical cavity through two-dimensional direct numerical simulations. The simulations encompassed a Rayleigh number (Ra) span of 107–1010, temperature difference (Δ θ ̃ ) up to 60 K, and a Prandtl number (Pr) fixed at 4.4. The center temperature ( θ cen ) was found to be independent of Ra and to increase linearly with Δ θ ̃ , as presented by θ cen ≈ 1.18 × 10 − 3 K − 1 Δ θ ̃ . The thermal boundary layer (BL) thicknesses near the hot and cold walls ( λ ¯ h θ and λ ¯ c θ , respectively) are found to scale as λ ¯ h , c θ ∼ R a γ λ ¯ h , c , where the scaling exponent γ λ ¯ h , c ranges from −0.264 to −0.262. For more detail, the scaling exponent γ λ ¯ h displays an increasing trend, while γ λ ¯ c demonstrates a decreasing trend. However, the sum of the hot and cold thermal BL thicknesses was found to be constant at a fixed Ra in the presence of NOB effects. Our detailed investigation of the Nusselt number (Nu) and Reynolds number (Re) revealed that N u ∼ R a 0.258 and R e ∼ R a 0.364 , showing insensitivity to NOB effects. These exponents were smaller than those for Rayleigh–Bénard convection. The NOB modifications on Nu and Re were less than 1.2% and 2.5%, respectively, even at Δ θ ̃ = 60 K. Our results also revealed that key parameters such as θ cen and normalized ratios [ ( λ ¯ NOB θ / λ ¯ OB θ) h , c , N u NOB / N u OB , and R e NOB / R e OB ] exhibit universal correlations with Δ θ ̃ . Remarkably, these relationships are consistent across varying Ra values. This observation underscored the influence of NOB effects on these parameters could be confidently forecasted using just the temperature difference (Δ θ ̃ ) for R a ∈ [ 10 7 , 10 10 ]. [ABSTRACT FROM AUTHOR]

This study proposes a highly stable and efficient monolithic immersed boundary projection method with staggered time discretization for particle sedimentation with heat transfer at density ratios near unity. To achieve the implicit coupling of fluid and solid motion, the proposed method uses a monolithic approach that incorporates temperature, fluid velocities, particle velocities, momentum forcing, energy forcing, and pressure. Subsequently, a two-step approximate lower–upper decomposition is used to decouple the complex large system. Two-dimensional and three-dimensional (3D) single particle sedimentation at various Grashof numbers and density ratios verifies the ability of the proposed method to handle particle sedimentation at density ratios near unity. Moreover, the proposed method demonstrates its clear advantages by successfully addressing both stability issues and spurious oscillations. Furthermore, simulation with the proposed method was performed for 3D two- and multi-particle sedimentation with heat transfer to demonstrate the robustness of the proposed method. The investigation of the effects of density ratio and Grashof numbers on particle sedimentation reveals a significant influence of buoyancy force, particularly for relatively lighter particles. An increase in the drag coefficient for multi-particle sedimentation is observed, owing to interactions between particles, and the Grashof number exerts a pronounced influence, particularly at low-density ratios. [ABSTRACT FROM AUTHOR]

We present a novel solver for simulating compressible multi-fluid multiphase flow in underwater explosions (UNDEXs). The developed solver uses a modified version of Saurel's six-equation model, which includes an additional total mixture energy equation to resolve discrepancies in the thermodynamic states predicted under shock conditions. Additionally, we integrate a more precise stiffened gas equation of state (SG-EOS) that is determined using a novel method to enhance the accuracy of predicting experimental data based on a shock Hugoniot curve. We also propose a solution procedure using the modified Saurel's six-equation model on a three-dimensional (3D) structured Cartesian grid system. This involves discretizing the equation system using a Godunov scheme with a two-fluid Harten-Lax-van Leer-Contact approximate Riemann solver and a MUSCL-Hancock primitive scheme with total-variation-diminishing limiters, achieving a second-order extension. Both the dimensional splitting and fractional-step methods are utilized to model one-dimensional (1D) operators, splitting them into sequential operators. The modified model is validated for 1D and 3D problems, including the water–air shock tube, cavitation, shock–bubble interaction, and UNDEX problems in a free field, near a free surface, and near a rigid dam. Our simulations accurately predict the shockwave propagation, shock and free-surface interactions, cavitation evolution, and water jetting impact characteristics, exhibiting satisfactory agreement with those of previous studies. The proposed solver provides insight into the effects of UNDEXs on rigid structures, with potential applications in engineering and defense. The proposed method for determining the SG-EOS parameters can be applied to other areas of research involving high-pressure multi-phase flows. [ABSTRACT FROM AUTHOR]

Non-Oberbeck–Boussinesq (NOB) effects in three representative fluids are quantitatively investigated in two-dimensional Rayleigh–Bénard convection. Numerical simulations are conducted in air, water, and glycerol with Prandtl numbers of P r = 0.71 , 4.4 , and 2547, respectively. We consider Rayleigh number R a ∈ [ 10 6 , 10 9 ] involving temperature difference (Δ θ ̃ ) of up to 60 K. The velocity and temperature profiles are found to be top-bottom antisymmetric under NOB conditions. As Pr increases, the time-averaged temperature of the cavity center ⟨ θ c ⟩ t increases under NOB conditions and the value of ⟨ θ c ⟩ t is only weakly influenced by Ra for all fluids. For Pr = 4.4 and 2547, with the enhancement of NOB effects, ⟨ θ c ⟩ t linearly increases and the maximum θ rms decreases/increases, and its location shifts toward/away from the wall near the bottom/top wall. Dispersed ⟨ θ c ⟩ t points and opposite phenomenon are observed in Pr = 0.71. The Nusselt number (Nu) and thermal boundary layer thickness at hot and cold walls ( λ ¯ h , c θ ) of the three fluids are comparable, and the Reynolds number (Re) significantly decreases as Pr increases. Under the NOB conditions with Pr = 4.4 and 2547, Nu decreases, Re increases, and λ ¯ h θ ( λ ¯ c θ ) thins (thickens) in an approximately linear fashion. Furthermore, the NOB effects on Nu, Re, and λ ¯ h , c θ are relatively small for Pr = 0.71 and 4.4, whereas the modifications caused by NOB effects at Pr = 2547 are more significant. The power-law scaling factors of Nu, Re, and λ ¯ h , c θ are demonstrated to be robust to Pr, as well as NOB effects. [ABSTRACT FROM AUTHOR]