Since its approval for clinical use more than two decades ago, memantine has become a blockbuster drug against Alzheimer's disease (AD). Unlike other FDA approved small molecules for the treatment of AD, essentially acetyl cholinesterase inhibitors, memantine behaves as N-methyl-d-aspartate (NMDA) receptor antagonist. However, it is a weak and non-specific NMDA receptor channel blocker that has shown to be safe in slowing the decline of moderate to advanced AD symptoms. In fact, those of us familiarized with AD, are aware of clinical protocols where memantine is usually prescribed to mitigate late stages of this neurological disorder, following previous treatment with donepezil and other inhibitors. The role of memantine for either preventing or disrupting amyloid formation, yet promising, remains unconclusive. The pharmacological basis and mode of action of memantine are well known and have been reviewed from different standpoints, often within the context of adamantane scaffolds. In recent times, further analyses combining experiment and computational simulation have disclosed subtle features of memantine-receptor interactions and previously unrecognized mechanistic insights, which are summarized herein. Likewise, there is a growing interest in memantine derivatives, not only against neurodegeneration, but also versus unrelated pathologies. Such studies arising from lab observations and preclinical assessments at most, point to memantine's repurposing and open the door to further explorations and translation. It is noteworthy that some structural aspects of memantine, including crystal packing and polymorphism, are usually overlooked. This review pays attention to such key elements and updates synthetic protocols, including the first preparation of memantine in continuous flow.

Sourness signature during Prunus mume fruit development: Integrative insight from metabolomics, organic acid profiles, E-tongue, and computational binding simulation.

Intraguild predation (IGP) regulates predator populations through direct predation and risk effects, shaping the life-history traits of intraguild prey. This study examines the impacts of IGP on life-history traits of two biocontrol agents, Neoseiulus barkeri and Scolothrips takahashii, reared on their shared prey Tetranychus urticae, using age-stage, two-sex life-table analysis and computer simulations. Life-table analysis revealed that IGP significantly reduced pre-adult survival of both predators. Neoseiulus barkeri developed faster, but exhibited reduced fecundity under IGP, which resulted in declines in its net reproductive rate (R0, from 30.76 to 10.51 offspring per individual), intrinsic rate of increase (r, from 0.2555 to 0.1872 day-1), and finite rate of increase (λ, from 1.2911 to 1.2059 day-1). Conversely, S. takahashii maintained stable development and fecundity, showing no significant differences in R0, r, λ and mean generation time (T) between IGP and control groups. The net predation rate (C0) of N. barkeri decreased from 381.00 to 172.97 prey per individual, and that of S. takahashii from 416.58 to 25.31, under IGP. Computer simulations indicated that IGP led to smaller populations and reduced predation potential for N. barkeri, whereas S. takahashii showed an increase in both. IGP differentially alters the population parameters and predation capacity of these two species. Neoseiulus barkeri experiences a decline in population growth, whereas S. takahashii benefits from IGP. These findings highlight species-specific adaptive strategies in response to IGP, providing insights for designing compatible multipredator application programs in biological control. © 2026 Society of Chemical Industry.

Laboratory-scale analyses of matrix-conduit exchange in a karst aquifer system using coupled physical and numerical modeling.

Public health response to a tuberculosis cluster in a high-rise apartment block.

Memory -dependent fake news dissemination and control: A fractional SVEIR model with stability analysis

Advances and adoptions of digital technology and computer simulation in engineering are driving the development of fully-automated methods for engineering analysis. The paper reviews the scaled boundary finite element method (SBFEM) and its salient features as a general-purpose tool for modern computational engineering. Emphasis is placed on its capacity on achieving a fully-automated framework suitable to high-performance computing. In the SBFEM, an element is constructed semi-analytically. The boundary of the element is discretized and the solution in the radial direction is obtained from the solution of ordinary differential equations. The SBFEM formulation can easily satisfy radiation boundary conditions and model stress singularities accurately using its analytical feature. Furthermore, it supports arbitrary polygonal and polyhedral elements. Recent advances have focused on integrating SBFEM with fully automated mesh generation techniques, such as octree and quadtree algorithms, enabling seamless workflows from multiple geometric modeling formats (e.g., digital images, point clouds, and CAD data) to computational analysis. This automation facilitates applications in dynamic response analysis, fracture mechanics, inverse problems, topology optimization, and high-performance computing.

Mathematical modelling and computer simulation are increasingly being used alongside experiments to help optimise and guide the design of drug delivery systems. Recent drug delivery research has (i) highlighted the advantages of drug delivery systems constructed using functionally-graded materials to achieve target release rates and desired dosage levels over time; and (ii) revealed how it is possible for drug to bind to the carrier material and become irreversibly immobilised within the system, reducing the amount of drug delivered. In this paper, we consider the effect of functionally-graded materials and binding reactions on drug release from common slab, cylinder and sphere devices. In particular, two key contributions are presented. First, we outline a deterministic-continuum approach that develops exact analytical expressions for calculating the total fraction of drug released from the device based on a partial differential equation model of the release process. Second, we develop a stochastic-discrete approach for calculating the fraction of drug released over time based on a random-walk model that captures the randomness of the release process and resulting variability in the total fraction of drug released. Both approaches are numerically validated and provide tools for exploring how the fraction of drug released depends on system parameters (e.g. diffusivity and reaction-rate functions induced by the functionally-graded material and binding reactions), insight which may be useful for designers of drug delivery systems. • Functionally-graded drug delivery systems with binding reactions. • Analytical and stochastic approaches for the fraction of drug released. • Analytical approach develops exact expressions based on PDE model. • Stochastic approach uses random-walk model of individual drug particles. • Code implementing and verifying both approaches provided.

Uncontrolled tipping during incisor retraction with clear aligners continues to limit orthodontic treatment. Different countermeasures have been proposed to improve the predictability of aligners, such as power ridges and attachments, while their efficacy requires further investigation. This work investigated the biomechanics of the overcorrection in reducing the tipping angle and moment during incisor retraction with a clear aligner, through in vitro experiments and finite element analysis (FEA). Specifically, the influence of overcorrection angle (1 deg), retraction distance (0.15 mm), and the combination of both were assessed through in vitro experiments and the finite element simulation. Further computational simulations were conducted to inspect the mechanical performance of clear aligners with different overcorrection angles (from 0 deg to 1 deg and 2 deg) for a fixed retraction distance of 0.15 mm. As the overcorrection angle increased from 0 deg to 1 deg and 2 deg for the clear aligner with a retraction of 0.15 mm, the tipping angle of the incisor decreased from 0.29 deg to 0.25 deg and 0.21 deg, and the tipping moment at the tooth root decreased from 13.60 N·mm to 9.38 N·mm and 6.27 N·mm. However, the retraction force also decreased from 0.84 N to 0.73 N and 0.47 N, indicating a tradeoff between tipping control and retraction efficiency, likely due to increased counteractive moment and the decreased force exerted by the aligner on the tooth crown. In conclusion, this study presents both the benefits and limitations of overcorrection strategies in reducing the tipping angle and moment during incisor retraction using clear aligners, providing biomechanical insight for the optimal design of clear aligners for improving treatment outcomes.

Development of coumarin-based acetylcholinesterase inhibitors: Synthesis, biological assessment and computational simulations.

Cardiomyocytes show considerable heterogeneity in action potential duration (APD) throughout the ventricles. Based on canine experiments, it has been proposed that a population of cells exhibiting extremely long APDs, the M-cells, is present in the midmyocardium. This cell type continues to be used in simulation studies. In this review, however, we argue against including them in computer models of the ventricles. Our argument is based on experimental findings reported by other research groups who have looked for M-cells in several species. Other than in the canine wedge model, M-cells are neither found consistently in the same locations nor as a large band, but rather as sparse, small islands. Using computer simulations, we demonstrate that M-cells are not required to explain the electrocardiogram and that their inclusion may result in non-physiological behaviour. Finally, as initially proposed, M-cells only manifest prolonged APD at extremely slow pacing rates, below sinus rhythm, and would not be seen in arrhythmias. Therefore, we conclude that there is no proof of a large enough population of M-cells to affect transmural APD, nor is it necessary, so M-cells should not be included in computer models.

BCL6 plays significant roles in various cellular processes and malignancies such as diffuse large B-cell lymphoma. BCL6 performs its functions through binding of its BTB domain to different corepressors. Thus, analyzing the possible structural consequences of nsSNPs on the function of this domain would be imperative. To this end, we have selected the most deleterious SNPs of BCL6 based on various scoring algorithms. Then the selected mutations were modeled, analyzed for various physicochemical and stability properties, and used for molecular docking with the BCoR, NCoR, and SMRT. The obtained complexes were used for the calculation of binding energy and depiction of 2D interaction plots. The docked complexes were also subjected to Molecular Dynamics (MD) simulations to screen their behavior in physiological conditions. The BCL6 SNPs were filtered to 54 nsSNPs of the BTB domain. Using various tools, these nsSNPs were narrowed down to the Q113K, V105G, I78T, and I60T mutations based on their deleteriousness and stability scores. Docking analyses indicated that the exerted mutations mostly reduced the binding affinity, and the MD simulations showed the lower stability of the mutated BCL6 forms during the simulation. Given the attained results, it could be concluded that selected nsSNPs could lead to impaired BCL6 transcriptional repressive function due to loss of stability and binding affinity towards its corepressors. These observations can explain various biological or clinical differences in individuals carrying these SNPs and help with the rational design of novel personalized therapeutics. The results found by computer simulations are suggesting new experiments that need to be done in the future to prove that they are biologically and clinically applicable.

Unlocking the potential of antimicrobial lipopeptides: a pathway to combat multidrug-resistant pathogens.

This study presents results of an effort to validate the numerical implementation of the thermo-hydro-mechanical model with thermo-osmosis in the finite-element simulator OpenGeoSys. The simulator’s capability to capture thermo-osmotic effects on pressure fields under thermal gradients is evaluated by comparison with a reference analytical solution and field data from the Mont Terri Deep Borehole experiment. The results demonstrate that the thermo-osmosis significantly influences subsurface pressure dynamics, and OpenGeoSys effectively reproduces this phenomenon. Additionally, an improved formulation of the THM process is outlined, and a model of the experiment is extended by inhomogeneous effects to reproduce the observed data better. This work illustrates how combining analytical verification, numerical modeling and field observations can improve the interpretation of complex THM processes in clay formations. • Validation of simulation software for thermo-osmosis based on borehole data. • Discussion of sources of uncertainty in thermo-osmosis models. • Tests of different hypotheses on physical phenomena to improve fit to data. • Variable geothermal gradients and permeability heterogeneity act synergistically. • Heterogeneity is important and has to be considered appropriately in the models.

Numerical modelling and analysis of impact failure of reinforced concrete structures using improved non-ordinary state-based peridynamics

This article presents the principles, software architecture, and performance analysis of the GPU port of the lattice Boltzmann software library Palabos [J. Latt et al., “Palabos: Parallel lattice Boltzmann solver”, Comput. Math. Appl. 81, 334–350, (2021)] . A hybrid CPU-GPU execution model is adopted, in which numerical components are selectively assigned to either the CPU or the GPU, depending on considerations of performance or convenience. This design enables a progressive porting strategy, allowing most features of the original CPU-based codebase to be gradually and seamlessly adapted to GPU execution. The new architecture builds upon two complementary paradigms: a classical object-oriented structure for CPU execution, and a data-oriented counterpart for GPUs, which reproduces the modularity of the original code while eliminating object-oriented overhead detrimental to GPU performance. Central to this approach is the use of modern C++, including standard parallel algorithms and template metaprogramming techniques, which permit the generation of hardware-agnostic computational kernels. This facilitates the development of user-defined, GPU-accelerated components such as collision operators or boundary conditions, while preserving compatibility with the existing codebase and avoiding the need for external libraries or non-standard language extensions. The correctness and performance of the GPU-enabled Palabos are demonstrated through a series of three-dimensional multiphysics benchmarks, including the laminar–turbulent transition in a Taylor–Green vortex, lid-driven cavity flow, and pore-scale flow in Berea sandstone. Despite the high-level abstraction of the implementation, the single-GPU performance is similar to CUDA-native solvers, and multi-GPU tests exhibit good weak and strong scaling across all test cases. Beyond the specific context of Palabos, the porting methodology illustrated here provides a generalizable framework for adapting large, complex C++ simulation codes to GPU architectures, while maintaining extensibility, maintainability, and high computational performance. Program Title: Palabos: Parallel Lattice Boltzmann Solver CPC Library link to program files: https://doi.org/10.17632/cx7j83pr69.1 Developer’s repository link: https://gitlab.com/unigespc/palabos Licensing provisions: AGPLv3 Programming language: C++17, using C++ parallel algorithms Supplementary material: A compressed file containing a snapshot of the described code version Nature of problem: The lattice Boltzmann method (LBM) is a widely used approach in computational fluid dynamics (CFD) for simulating flows in complex geometries, turbulence, multiphase systems, and thermal transport. The Palabos library was designed to provide the scientific community with a flexible and efficient parallel LBM platform, implementing a broad range of physical and numerical models. Until now, Palabos has been CPU-based, relying on distributed-memory parallelism through MPI. However, with modern simulation platforms and supercomputers increasingly dominated by GPU accelerators, a CPU-only implementation no longer provides competitive performance. This work presents a complete redesign of the Palabos architecture to run efficiently on multi-GPU systems. The new code supports hybrid execution: legacy CPU components remain functional, new GPU-optimized modules can be developed within a compatible programming model, and both can interact seamlessly. This version supersedes the original CPU-only implementation and will serve as the basis for all future development of Palabos. Solution method: The GPU version of Palabos introduces a new data container, the AcceleratedLattice , designed specifically for accelerator execution. It preserves the user interface of the CPU-based MultiBlockLattice , but replaces its array-of-structures layout and virtual-function polymorphism with a structure-of-arrays layout, thread-safe collision–streaming schemes, and integer tags for model selection. These changes enable efficient memory access, fine-grained parallelism, and compatibility with GPU execution models, while maintaining backward compatibility and supporting hybrid CPU/GPU workflows. Parallelism is expressed through C++17 standard parallel algorithms, compiled with the NVIDIA HPC SDK. Fundamental parallel algorithms such as for_each , transform_reduce , and exclusive_scan are used to implement the essential building blocks of the lattice Boltzmann method, including linear processing, reductions, and data packing for MPI communication. This data-oriented design yields a portable and maintainable GPU implementation, preserves modularity, and ensures that existing Palabos applications can be ported to GPU with minimal modifications. Additional comments including restrictions and unusual features: The GPU version currently relies on the platform-independent framework of C++ parallel algorithms but has, as of now, only been tested with NVIDIA GPUs (compiled with nvc++) supports NVIDIA architectures with CUDA-compatible compilers (tested with nvc++). The current version of the code does not compile with the 25.X series of the nvc++ compiler.

The damage mechanism and dynamic response of a double-layered Portal pier under explosion load

Validating sideband peak count-index (SPC-I) technique as a hybrid linear/nonlinear ultrasonic technique through numerical modeling and experiment.

The long-term risks of marine oil pollution to biodiversity, fisheries, and human health necessitate effective oil spill assessments in coastal management, particularly in highly ship-trafficked regions like the East China Sea (ECS). Numerical models, especially Lagrangian models, excel in simulating oil spill behavior under diverse meteorological conditions and incorporating complex processes like weathering. In this study, gaps in prior research are addressed by evaluating the performance of the Lagrangian GNOME model, coupled with the ADIOS, in relation to the disastrous Sanchi incident that happened in the ECS. This assessment is notable for its extended spatiotemporal resolution of Sanchi oil spill modeling. The models of this study were configured to simulate key processes for both heavy fuel oil (HFO) and condensate, and validation was achieved through location comparison between remotely observed and simulated oil spills. Subsequently, the obtained results indicated that one year post-release, 132 metric tons of HFO had evaporated and 101 metric tons had become stranded along shorelines, while 687 metric tons of condensate disappeared from the water surface within approximately 8 hours. Spatial analysis identified Japanese coastal zones as the most impacted, where the interplay of meteorological conditions resulted in 29,000 kilograms of oil beaching. The obtained results confirm the efficacy of the GNOME in a high-traffic shipping zone such as the ECS as an environmental management system for refining spill response strategies and environmental risk management, while also emphasizing the necessity of long-term oil pollution assessments, as oil slicks persisted for a year after the incident.

Magma degassing controlling the formation of porphyry copper deposits: A dynamic analysis through numerical modeling