Search Results (25)

Quantitative structure–activity relationship (QSAR) modeling has conventionally relied on expert-designed molecular descriptors to encode chemical structures. DeepSnap is a descriptor-free QSAR approach that converts prepared three-dimensional molecular conformers into image representations and feeds them directly into convolutional neural networks for activity prediction. This focused narrative review traces DeepSnap from its introduction in 2018 to its current state and places it within the broader landscape of descriptor-based QSAR, topology-based and 3D-aware graph neural networks, and related image-based or semi-image-based molecular representation approaches. Previous studies applied DeepSnap to Tox21 nuclear receptor and molecular initiating event endpoints, rat hepatic clearance, blood–brain barrier penetration, acute oral toxicity, and cosmetics–pharmaceutical compound classification. Across the DeepSnap series, image-based and descriptor-based predictions have provided complementary information, particularly in ensemble or consensus models. However, high or near-ceiling ROC–AUC values reported for selected endpoints should not be interpreted as indicating deterministic or universally generalizable predictions; rather, they should be considered in the context of endpoint-specific model development, image-rendering parameter optimization, possible class imbalance, split dependence, limited matched external replication, and incomplete benchmarking against modern molecular representation models. Limitations include a dependence on nonphysical rendering parameters, single- or representative-conformer input, incomplete matched benchmarking against 2D and 3D molecular representation models, and an interpretability gap addressed in part by CAM-family visualization in the AI-based Substance Hazard Integrated Prediction System (AI-SHIPS) and S-COPHY (a model developed by Shiseido for cosmetics–pharmaceutical compound classification). Future directions include standardized image-generation protocols, conformer-ensemble extensions, systematic interpretability analysis, matched benchmarking, and potential integration with graph-based and 3D-aware molecular learning approaches. Full article

Background/Objectives: Population-specific genomic data are essential for understanding hepatocellular carcinoma (HCC) biology, particularly in underrepresented regions. This study aimed to perform exploratory single-nucleotide polymorphism (SNP)-array-based profiling of HCC tumor samples from Indonesian patients and to prioritize candidate functional variants using a systematic in silico framework. Methods: This retrospective cross-sectional study included 15 resected HCC cases with available formalin-fixed paraffin-embedded (FFPE) tumor tissue. Genome-wide SNP genotyping was performed using the Illumina Asian Screening Array. Following quality control and filtering, variants were annotated using the Ensembl Variant Effect Predictor. A case-only functional prioritization approach incorporating multiple in silico prediction tools was applied, followed by gene-level burden aggregation. Results: After multistep filtering, 11 samples and 104 prioritized variants were retained for analysis. Variants consisted predominantly of splice-region, missense, and regulatory changes. Gene-level burden analysis identified Nuclear Autoantigenic Sperm Protein (NASP, rs775916096) as the highest-ranked candidate gene, while G protein-coupled receptor 78 (GPR78, rs558447540) emerged as a secondary candidate with predicted functional annotations but currently limited biological evidence in HCC. Given the tumor-only design without matched normal tissue, the prioritized variants cannot be distinguished from rare germline variants. Conclusions: This exploratory SNP-array study provides a hypothesis-generating framework for functional variant prioritization in Indonesian HCC. NASP and GPR78 represent preliminary candidates that require validation in larger cohorts with matched normal tissue and sequencing-based confirmation. Full article

Background: This study employed artificial intelligence (AI) to analyze quantitative nuclear morphological features obtained from digital pathology images to predict postoperative recurrence in patients with lung squamous cell carcinoma (LSQCC). We aimed to develop a prediction model that contributes to the realization of ‘personalized postoperative management’ tailored to individual tumor biology by integrating AI-extracted morphological features with clinical information. Methods: A total of 185 of the 253 surgically resected LSQCC cases were included; 136 were randomly assigned to the training set and 49 to the test set. Nuclear features from manually selected regions of interest were extracted and used to build AI-based prediction models. Three recurrence models were developed: recurrence within 2 years, within 5 years, and a three-category model (≤2 years, 3–5 years, >5 years or no recurrence). Support vector machine (SVM) and random forest (RF) algorithms were applied to each, yielding six predictive models. An ensemble approach was used to calculate AI-based risk scores, and a “total risk score” was developed by integrating these with the pathologic stage. Results: All six AI models demonstrated stable predictive performance, with AUC values ranging from 0.76 to 0.91. Kaplan–Meier analysis showed that the total risk score provided the most precise risk stratification (p < 0.005), with clearer separation between risk groups than the AI-based risk score alone. Conclusions: The integration of AI-based nuclear morphology analysis and clinical data provides an objective and practical tool for personalized postoperative management in LSQCC. This approach enables tailored clinical decision-making by identifying patients at high risk for early recurrence and customizing postoperative treatment plans to meet the specific needs of each individual. Full article

Allosteric modulation has emerged as a powerful strategy for achieving superior selectivity and safety in drug discovery and protein function regulation. Unlike highly conserved orthosteric sites, allosteric pockets are structurally diverse and less evolutionarily constrained, making them particularly suitable for modulation by designed miniproteins. Miniproteins can provide extended binding interfaces and high affinity for shallow, dynamic, or cryptic regulatory surfaces that are often inaccessible to small molecules. Recent advances in artificial intelligence (AI) are transforming this field through deep learning-based structure prediction and generative modeling. These AI-driven approaches enable the identification of allosteric hotspots, characterization of conformational ensembles, and de novo design of structured miniprotein binders. They are rapidly expanding the landscape for designing selective modulators across diverse allosteric targets, including GPCRs, receptor tyrosine kinases, nuclear receptors, ion channels, and other protein–protein interaction systems. This review summarizes state-of-the-art AI-driven computational methodologies for designing miniproteins as potential allosteric modulators and discusses their current challenges and future opportunities in allosteric drug discovery. Full article

Realistic atomistic modeling of mineral and soil systems requires chemically meaningful representations of organic matter (OM). Bulk ¹³C nuclear magnetic resonance (NMR) data have been proposed as compositional inputs for stochastic generation of OM structures, and prior studies using nonnegative multivariate curve resolution (MCR) suggested that bulk ¹³C NMR spectra of OM may be represented as mixtures of only a few components. However, these studies typically relied on single-block decompositions and did not explicitly assess decomposition uniqueness. The objective of this work was to examine whether a quantitative and chemically interpretable nonnegative MCR decomposition of OM can be obtained while explicitly evaluating (1) residual rotational ambiguity controlling the uniqueness of components, and (2) the variance captured by the decomposition. Using a dataset of International Humic Substances Society (IHSS) humic acids, fulvic acids, and aquatic OM, we applied single- and multi-block nonnegative MCR–alternating least squares (ALS) analyses integrating ¹³C NMR spectra, elemental composition (C, H, O, N, S), and titratable carboxylic and phenolic group contents. The multi-block approach effectively narrowed the feasible solution space and enriched the chemical characterization of the resulting MCR components. Across all analytical blocks, two chemically distinct components, an aromatic-rich and an aliphatic-rich motifs, consistently emerged, together explaining ~97–98% of the total variance and exhibiting near-zero residual rotational ambiguity. These findings support that diverse OM types can be represented quantitatively as mixtures of a small set of unique recurring compositional motifs. These motifs serve as ensemble-level averages whose underlying molecular diversity may vary substantially across materials. They provide quantitative, chemically justified inputs for molecular modeling of mineral–OM systems, which could contribute to chemical interpretability of modeling and provide better mechanistic insights into OM variation across diverse sample series. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a multifactorial condition requiring multi-target therapeutic strategies beyond traditional single-marker approaches. In this work, we present a fully in silico nutraceutical screening pipeline that integrates molecular prediction, systemic aggregation, and technological design. A curated panel of ten MASLD-relevant targets, spanning nuclear receptors (FXR, PPAR-α/γ, THR-β), lipogenic and cholesterogenic enzymes (ACC1, FASN, DGAT2, HMGCR), and transport/regulatory proteins (LIPG, FABP4), was assembled from proteomic evidence. Bioactivity records were extracted from ChEMBL, structurally standardized, and converted into RDKit descriptors. Predictive modeling employed a stacked ensemble of Random Forest, XGBoost, and CatBoost with isotonic calibration, yielding robust performance (mean cross-validated ROC-AUC 0.834; independent test ROC-AUC 0.840). Calibrated probabilities were aggregated into total activity (TA) and weighted TA metrics, combined with structural clustering (six structural clusters, twelve MOA clusters) to ensure chemical diversity. We used physiologically based pharmacokinetic (PBPK) modeling to translate probabilistic profiles into minimum simulated doses (MSDs) and chrono-specific exposure (%T>IC50) for three prototype concepts: HepatoBlend (morning powder), LiverGuard Tea (evening aqueous form), and HDL-Chews (postprandial chew). Integration of physicochemical descriptors (MW, logP, TPSA) guided carrier and encapsulation choices, addressing stability and sensory constraints. The results demonstrate that a computationally integrated pipeline can rationally generate multi-target nutraceutical formulations, linking molecular predictions with systemic coverage and practical formulation specifications, and thus provides a transferable framework for MASLD and related metabolic conditions. Full article

Intelligent fault diagnosis (IFD) plays a crucial role in reducing maintenance costs and enhancing the reliability of safety-critical energy systems (SCESs). In recent years, deep learning-based IFD methods have achieved high fault diagnosis accuracy extracting implicit higher-order correlations between features. However, the excessive long training time of deep learning models conflicts with the requirements of real-time analysis for IFD, hindering their further application in practical industrial environments. To address the aforementioned challenge, this paper proposes an innovative IFD method for SCES that combines the particle swarm optimization (PSO) algorithm and the ensemble broad learning system (EBLS). Specifically, the broad learning system (BLS), known for its low time complexity and high classification accuracy, is adopted as an alternative to deep learning for fault diagnosis in SCES. Furthermore, EBLS is designed to enhance model stability and classification accuracy with high-dimensional small samples by incorporating the random forest (RF) algorithm and an ensemble strategy into the traditional BLS framework. In order to reduce the computational cost of the EBLS, which is constrained by the selection of its hyperparameters, the PSO algorithm is employed to optimize the hyperparameters of the EBLS. Finally, the model is validated through simulated data from a complex nuclear power plant (NPP). Numerical experiments reveal that the proposed method significantly improved the diagnostic efficiency while maintaining high accuracy. In summary, the proposed approach shows great promise for boosting the capabilities of the IFD models for SCES. Full article

State-of-the-art hydrogeological investigations use transient calibrated numerical flow and transport models for multiple scenario analyses. However, the transient calibration of numerical flow and transport models still requires consistent long-term groundwater time series, which are often not available or contain data gaps, thus reducing the robustness and confidence of the numerical model. This study presents a data-driven approach for the reconstruction and prediction of gaps in a discontinuous groundwater level time series at a monitoring station in the Allertal (Saxony-Anhalt, Germany). Deep Learning and classical machine learning (ML) approaches (artificial neural networks (TensorFlow, PyTorch), the ensemble method (Random Forest), boosting method (eXtreme gradient boosting (XGBoost)), and Multiple Linear Regression) are used. Precipitation and groundwater level time series from two neighboring monitoring stations serve as input data for the prediction and reconstruction. A comparative analysis shows that the input data from one measuring station enable the reconstruction and prediction of the missing groundwater levels with good to satisfactory accuracy. Due to a higher correlation between this station and the station to be predicted, its input data lead to better adapted models than those of the second station. If the time series of the second station are used as model inputs, the results show slightly lower correlations for training, testing and, prediction. All machine learning models show a similar qualitative behavior with lower fluctuations during the hydrological summer months. The successfully reconstructed and predicted time series can be used for transient calibration of numerical flow and transport models in the Allertal (e.g., for the overlying rocks of the Morsleben Nuclear Waste Repository). This could lead to greater acceptance, reliability, and confidence in further numerical studies, potentially addressing the influence of the overburden acting as a barrier to radioactive substances. Full article

Hydroperoxymethyl thioformate (or HPMTF) is a compound relevant to the chemistry of sulfur in the marine atmosphere. The chemical cycling of this molecule in the atmosphere is still uncertain due in part to the lack of accurate knowledge of its photolytic behavior. Only approximations based on the properties of its chromophores are used in previous studies. In this work, we calculated the absorption spectra of the molecule in gas and aqueous phases using the Nuclear Ensemble Approach (NEA) and the CASPT2 method. Furthermore, we used such information to obtain relative photolysis rates. We found that the chromophore approximation overestimates the photolysis rates in the gas phase by twice the value obtained with the NEA-CASPT2 protocol. Furthermore, for the aqueous phase, we predict a lower role of photolysis as compared to the gas phase. Full article

The Dicentric Chromosome Assay (DCA) is widely used in biological dosimetry, where the number of dicentric chromosomes induced by ionizing radiation (IR) exposure is quantified to estimate the absorbed radiation dose an individual has received. Dicentric chromosome scoring is a laborious and time-consuming process which is performed manually in most cytogenetic biodosimetry laboratories. Further, dicentric chromosome scoring constitutes a bottleneck when several hundreds of samples need to be analyzed for dose estimation in the aftermath of large-scale radiological/nuclear incident(s). Recently, much interest has focused on automating dicentric chromosome scoring using Artificial Intelligence (AI) tools to reduce analysis time and improve the accuracy of dicentric chromosome detection. Our study aims to detect dicentric chromosomes in metaphase plate images using an ensemble of artificial neural network detectors suitable for datasets that present a low number of samples (in this work, only 50 images). In our approach, the input image is first processed by several operators, each producing a transformed image. Then, each transformed image is transferred to a specific detector trained with a training set processed by the same operator that transformed the image. Following this, the detectors provide their predictions about the detected chromosomes. Finally, all predictions are combined using a consensus function. Regarding the operators used, images were binarized separately applying Otsu and Spline techniques, while morphological opening and closing filters with different sizes were used to eliminate noise, isolate specific components, and enhance the structures of interest (chromosomes) within the image. Consensus-based decisions are typically more precise than those made by individual networks, as the consensus method can rectify certain misclassifications, assuming that individual network results are correct. The results indicate that our methodology worked satisfactorily in detecting a majority of chromosomes, with remarkable classification performance even with the low number of training samples utilized. AI-based dicentric chromosome detection will be beneficial for a rapid triage by improving the detection of dicentric chromosomes and thereby the dose prediction accuracy. Full article

Protein dynamics play a crucial role in biological function, encompassing motions ranging from atomic vibrations to large-scale conformational changes. Recent advancements in experimental techniques, computational methods, and artificial intelligence have revolutionized our understanding of protein dynamics. Nuclear magnetic resonance spectroscopy provides atomic-resolution insights, while molecular dynamics simulations offer detailed trajectories of protein motions. Computational methods applied to X-ray crystallography and cryo-electron microscopy (cryo-EM) have enabled the exploration of protein dynamics, capturing conformational ensembles that were previously unattainable. The integration of machine learning, exemplified by AlphaFold2, has accelerated structure prediction and dynamics analysis. These approaches have revealed the importance of protein dynamics in allosteric regulation, enzyme catalysis, and intrinsically disordered proteins. The shift towards ensemble representations of protein structures and the application of single-molecule techniques have further enhanced our ability to capture the dynamic nature of proteins. Understanding protein dynamics is essential for elucidating biological mechanisms, designing drugs, and developing novel biocatalysts, marking a significant paradigm shift in structural biology and drug discovery. Full article

Forecasting nuclear energy production is essential for market operations such as security, economic efficiency, resource optimization, grid stability, and the integration of renewable energy sources. Forecasting approaches allow nuclear power plants to operate consistently, contributing to the overall reliability and long-term viability of the energy system. It is noted that energy systems researchers are increasingly interested in machine learning models used to face the challenge of time series forecasting. This study evaluates a hybrid ensemble learning of three time series forecasting models including least-squares support vector regression, gated recurrent unit, and long short-term memory models applied to nuclear power time series forecasting on the dataset of French power plants from 2009 to 2020. Furthermore, this research evaluates forecasting results in which approaches are directed towards the optimized RreliefF (Robust relief Feature) selection algorithm using a hyperparameter optimization based on tree-structured Parzen estimator and following an ensemble learning approach, showing promising results in terms of performance metrics. The suggested ensemble learning model, which combines deep learning and the RreliefF algorithm using a hold-out, outperforms the other nine forecasting models in this study according to performance criteria such as 75% for the coefficient of determination, a root squared error average of 0.108, and an average absolute error of 0.080. Full article

Nuclear Integrated Energy Systems (NIES) have emerged as a comprehensive solution for navigating the changing energy landscape. They combine nuclear power plants with renewable energy sources, storage systems, and smart grid technologies to optimize energy production, distribution, and consumption across sectors, improving efficiency, reliability, and sustainability while addressing challenges associated with variability. The integration of Small Modular Reactors (SMRs) in NIES offers significant benefits over traditional nuclear facilities, although transferring involves overcoming legal and operational barriers, particularly in economic dispatch. This study proposes a novel off-policy Reinforcement Learning (RL) approach with an ensemble reward system to optimize economic dispatch for nuclear-powered generation companies equipped with an SMR, demonstrating superior accuracy and efficiency when compared to conventional methods and emphasizing RL’s potential to improve NIES profitability and sustainability. Finally, the research attempts to demonstrate the viability of implementing the proposed integrated RL approach in spot energy markets to maximize profits for nuclear-driven generation companies, establishing NIES’ profitability over competitors that rely on fossil fuel-based generation units to meet baseload requirements. Full article

The study of the human psyche has elucidated a bipartite structure of logic reflecting the quantum–classical nature of the world. Accordingly, we posited an approach toward studying the brain by means of the quantum–classical dynamics of a mixed Weyl symbol. The mixed Weyl symbol can be used to describe brain processes at the microscopic level and, when averaged over an appropriate ensemble, can provide a link to the results of measurements made at the meso and macro scale. Within this approach, quantum variables (such as, for example, nuclear and electron spins, dipole momenta of particles or molecules, tunneling degrees of freedom, and so on) can be represented by spinors, whereas the electromagnetic fields and phonon modes can be treated either classically or semi-classically in phase space by also considering quantum zero-point fluctuations. Quantum zero-point effects can be incorporated into numerical simulations by controlling the temperature of each field mode via coupling to a dedicated Nosé–Hoover chain thermostat. The temperature of each thermostat was chosen in order to reproduce quantum statistics in the canonical ensemble. In this first paper, we introduce a general quantum–classical Hamiltonian model that can be tailored to study physical processes at the interface between the quantum and the classical world in the brain. While the approach is discussed in detail, numerical calculations are not reported in the present paper, but they are planned for future work. Our theory of brain dynamics subsumes some compatible aspects of three well-known quantum approaches to brain dynamics, namely the electromagnetic field theory approach, the orchestrated objective reduction theory, and the dissipative quantum model of the brain. All three models are reviewed. Full article

Gekko is an optimization suite in Python that solves optimization problems involving mixed-integer, nonlinear, and differential equations. The purpose of this study is to integrate common Machine Learning (ML) algorithms such as Gaussian Process Regression (GPR), support vector regression (SVR), and artificial neural network (ANN) models into Gekko to solve data based optimization problems. Uncertainty quantification (UQ) is used alongside ML for better decision making. These methods include ensemble methods, model-specific methods, conformal predictions, and the delta method. An optimization problem involving nuclear waste vitrification is presented to demonstrate the benefit of ML in this field. ML models are compared against the current partial quadratic mixture (PQM) model in an optimization problem in Gekko. GPR with conformal uncertainty was chosen as the best substitute model as it had a lower mean squared error of 0.0025 compared to 0.018 and more confidently predicted a higher waste loading of 37.5 wt% compared to 34 wt%. The example problem shows that these tools can be used in similar industry settings where easier use and better performance is needed over classical approaches. Future works with these tools include expanding them with other regression models and UQ methods, and exploration into other optimization problems or dynamic control. Full article