Land use expansion is linked to major sustainability concerns including climate change, food security and biodiversity loss. This expansion is largely concentrated in so-called frontiers, defined here as places experiencing marked transformations due to rapid resource exploitation. Understanding the mechanisms shaping these frontiers is crucial for sustainability. Previous work focused mainly on explaining how active frontiers advance, in particular into tropical forests. Comparatively, our understanding of how frontiers emerge in territories considered marginal in terms of agricultural productivity and global market integration remains weak. We synthesize conceptual tools explaining resource and land-use frontiers, including theories of land rent and agglomeration economies, of frontiers as successive waves, spaces of territorialization, friction, and opportunities, anticipation and expectation. We then propose a new theory of frontier emergence, which identifies exogenous pushes, legacies of past waves, and actors anticipations as key mechanisms by which frontiers emerge. Processes of abnormal rent creation and capture and the built-up of agglomeration economies then constitute k
The contributions of model complexity, data volume, and feature modalities to knowledge graph-based drug repurposing remain poorly quantified under rigorous temporal validation. We constructed a pharmacology knowledge graph from ChEMBL 36 comprising 5,348 entities including 3,127 drugs, 1,156 proteins, and 1,065 indications. A strict temporal split was enforced with training data up to 2022 and testing data from 2023 to 2025, together with biologically verified hard negatives mined from failed assays and clinical trials. We benchmarked five knowledge graph embedding models and a standard graph neural network with 3.44 million parameters that incorporates drug chemical structure using a graph attention encoder and ESM-2 protein embeddings. Scaling experiments ranging from 0.78 to 9.75 million parameters and from 25 to 100 percent of the data, together with feature ablation studies, were used to isolate the contributions of model capacity, graph density, and node feature modalities. Removing the graph attention based drug structure encoder and retaining only topological embeddings combined with ESM-2 protein features improved drug protein PR-AUC from 0.5631 to 0.5785 while reducing V
Physics-Informed Kolmogorov-Arnold Networks (PIKANs) are gaining attention as an effective counterpart to the original multilayer perceptron-based Physics-Informed Neural Networks (PINNs). Both representation models can address inverse problems and facilitate gray-box system identification. However, a comprehensive understanding of their performance in terms of accuracy and speed remains underexplored. In particular, we introduce a modified PIKAN architecture, tanh-cPIKAN, which is based on Chebyshev polynomials for parametrization of the univariate functions with an extra nonlinearity for enhanced performance. We then present a systematic investigation of how choices of the optimizer, representation, and training configuration influence the performance of PINNs and PIKANs in the context of systems pharmacology modeling. We benchmark a wide range of first-order, second-order, and hybrid optimizers, including various learning rate schedulers. We use the new Optax library to identify the most effective combinations for learning gray-boxes under ill-posed, non-unique, and data-sparse conditions. We examine the influence of model architecture (MLP vs. KAN), numerical precision (single
Object Goal Navigation (OGN) is a fundamental task for robots and AI, with key applications such as mobile robot image databases (MRID). In particular, mapless OGN is essential in scenarios involving unknown or dynamic environments. This study aims to enhance recent modular mapless OGN systems by leveraging the commonsense reasoning capabilities of large language models (LLMs). Specifically, we address the challenge of determining the visiting order in frontier-based exploration by framing it as a frontier ranking problem. Our approach is grounded in recent findings that, while LLMs cannot determine the absolute value of a frontier, they excel at evaluating the relative value between multiple frontiers viewed within a single image using the view image as context. We dynamically manage the frontier list by adding and removing elements, using an LLM as a ranking model. The ranking results are represented as reciprocal rank vectors, which are ideal for multi-view, multi-query information fusion. We validate the effectiveness of our method through evaluations in Habitat-Sim.
The morphological form of a word can often give cues to its meaning, but purely relying on these mappings can lead to overgeneralization in high-stakes domains. In the medical domain, for instance, LLMs can confidently reason about fictitious drugs from their affixes alone (e.g., wugcillin) and generate plausible-looking clinical content. We present a behavioral and mechanistic study of LLM "affix heuristics" in pharmacology. Using fictitious drug names built from real affixes, we show that affix signals alone elicit class-level pharmacological responses. We introduce a framework for identifying whether a model's drug semantics are driven mainly by the affix, the stem, or the drug name as a whole. Applied across 653 drugs, our framework reveals that models often induce drug meaning primarily through affix cues, yet rarely explicitly indicate this reliance, and sometimes incorrectly conflate properties among affix-sharing drugs. Activation patching across models further localizes this behavior to early-mid layers. These findings show that morphological shortcuts pose a subtle but measurable risk to safety.
Objective: To investigate the mechanism by which quercetin inhibits triple-negative breast cancer (TNBC) through regulating T-cell-related targets, providing a novel strategy for TNBC immunotherapy.Methods: Single-cell RNA sequencing (GSE161529 dataset) and network pharmacology were integrated. PCA and UMAP clustering identified T-cell subsets and differentially expressed genes in TNBC microenvironment. TNBC-related targets were screened via CTD and OMIM databases, with functional pathways analyzed by GO/KEGG enrichment. Molecular docking and PPI networks validated interactions between quercetin and core targets.Results: Quercetin intersected with 79 TNBC targets, including AKT1, EGFR, and MMP9, enriched in EGFR inhibitor resistance and endocrine resistance pathways. Molecular docking revealed the highest affinity between quercetin and GSK3B (-13.2 kJ/mol). AKT1 and MMP9 expression correlated with patient survival.Conclusion: Quercetin may reverse TNBC immunosuppression by multi-target modulation of T-cell function, but clinical application requires solutions for its low bioavailability, such as delivery systems or combination therapies.
Zero-shot open-vocabulary object navigation has progressed rapidly with the emergence of large Vision-Language Models (VLMs) and Large Language Models (LLMs), now widely used as high-level decision-makers instead of end-to-end policies. Although effective, such systems often rely on iterative large-model queries at inference time, introducing latency and computational overhead that limit real-time deployment. To address this problem, we repurpose ray frontiers (R2F), a recently proposed frontier-based exploration paradigm, to develop an LLM-free framework for indoor open-vocabulary object navigation. While ray frontiers were originally used to bias exploration using semantic cues carried along rays, we reinterpret frontier regions as explicit, direction-conditioned semantic hypotheses that serve as navigation goals. Language-aligned features accumulated along out-of-range rays are stored sparsely at frontiers, where each region maintains multiple directional embeddings encoding plausible unseen content. In this way, navigation then reduces to embedding-based frontier scoring and goal tracking within a classical mapping and planning pipeline, eliminating iterative large-model reason
Stochastic Multi-Objective Optimization (SMOO) is critical for decision-making trading off multiple potentially conflicting objectives in uncertain environments. SMOO aims at identifying the Pareto frontier, which contains all mutually non-dominating decisions. The problem is highly intractable due to the embedded probabilistic inference, such as computing the marginal, posterior probabilities, or expectations. Existing methods, such as scalarization, sample average approximation, and evolutionary algorithms, either offer arbitrarily loose approximations or may incur prohibitive computational costs. We propose XOR-SMOO, a novel algorithm that with probability $1-δ$, obtains $γ$-approximate Pareto frontiers ($γ>1$) for SMOO by querying an SAT oracle poly-log times in $γ$ and $δ$. A $γ$-approximate Pareto frontier is only below the true frontier by a fixed, multiplicative factor $γ$. Thus, XOR-SMOO solves highly intractable SMOO problems (\#P-hard) with only queries to SAT oracles while obtaining tight, constant factor approximation guarantees. Experiments on real-world road network strengthening and supply chain design problems demonstrate that XOR-SMOO outperforms several baseli
Large language models (LLMs) have shown strong empirical performance across pharmacology and drug discovery tasks, yet the internal mechanisms by which they encode pharmacological knowledge remain poorly understood. In this work, we investigate how drug-group semantics are represented and retrieved within Llama-based biomedical language models using causal and probing-based interpretability methods. We apply activation patching to localize where drug-group information is stored across model layers and token positions, and complement this analysis with linear probes trained on token-level and sum-pooled activations. Our results demonstrate that early layers play a key role in encoding drug-group knowledge, with the strongest causal effects arising from intermediate tokens within the drug-group span rather than the final drug-group token. Linear probing further reveals that pharmacological semantics are distributed across tokens and are already present in the embedding space, with token-level probes performing near chance while sum-pooled representations achieve maximal accuracy. Together, these findings suggest that drug-group semantics in LLMs are not localized to single tokens but
Language models encode text as subword tokens, raw bytes, or rendered pixels, but these encodings are usually compared under modeling constraints that expose different amounts of linguistic content to models across different languages. We instead ask what each encoding preserves when both the content and the downstream capacity are controlled. Using verified parallel sentences across thirteen languages and five scripts, we compare tokens, bytes, and pixels through a shared bottleneck whose width is swept to trace rate-utility frontiers. This separates three quantities that are often conflated: the number of input positions an encoding creates, the latent capacity available after encoding, and the task-relevant information that survives compression. We evaluate three utilities: surface form preservation, cross-lingual sentence alignment, and topic classification. No encoding dominates across tasks or capacity regimes. Pixels preserve surface form best, bytes preserve cross-lingual alignment best, especially in same-script multilingual settings, and tokens support topic prediction best. These performances are not explained by sequence length alone. Short inputs can discard useful mea
Chronic superficial gastritis (CSG) severely affects quality of life and can progress to worse gastric pathologies. Traditional Chinese Medicine (TCM) effectively treats CSG, as exemplified by Jinhong Tablets (JHT) with known anti-inflammatory properties, though their mechanism remains unclear. This study integrated network pharmacology, untargeted metabolomics, and gut microbiota analyses to investigate how JHT alleviates CSG. A rat CSG model was established and evaluated via H&E staining. We identified JHT's target profiles and constructed a multi-layer biomolecular network. Differential metabolites in plasma were determined by untargeted metabolomics, and gut microbiota diversity/composition in fecal and cecal samples was assessed via 16S rRNA sequencing. JHT markedly reduced gastric inflammation. Network pharmacology highlighted metabolic pathways, particularly lipid and nitric oxide metabolism, as essential to JHT's therapeutic effect. Metabolomics identified key differential metabolites including betaine (enhancing gut microbiota), phospholipids, and citrulline (indicating severity of CSG). Pathway enrichment supported the gut microbiota's involvement. Further microbiota
Recommending safe and effective medication combinations from electronic health records (EHRs) is a core clinical AI problem, yet it remains difficult because patient trajectories are long, noisy, and clinically heterogeneous. Existing methods typically excel at either temporal modeling across visits or pharmacological knowledge integration (e.g., drug-drug interactions, DDIs), but rarely achieve both while robustly suppressing noise. We present GraphDiffMed, a knowledge-constrained medication recommendation framework built on dual-scale Differential Attention v2. Differential attention is applied at both intra-visit and inter-visit levels to filter spurious signals within encounters and across longitudinal history, while pharmacological constraints are incorporated during learning. Experiments on MIMIC-III and ablation studies show that this design consistently improves recommendation quality and ranking over strong baselines while achieving a more favorable safety performance balance. We further find that the strongest-performing configuration uses only demographic auxiliary features under our experimental setting. Overall, GraphDiffMed demonstrates that combining noise-aware atte
Artificial intelligence (AI) agents promise to accelerate drug discovery by compressing interpretation and decision-making loops, but practical deployment requires trusted evaluation on realistic program decisions. We introduce TherapeuticsBench Preclinical Pharmacology (TxBench-PP), a verifiable benchmark for small-molecule preclinical pharmacology and the first focused slice of a broader TherapeuticsBench effort across drug-discovery stages and therapeutic modalities. TxBench-PP tests whether agents can recover accurate conclusions from real-world assay data rather than memorized facts from literature. The benchmark contains 100 evaluations indexed by program stage, assay type, and task structure, spanning mechanism-of-action (MoA) and pharmacodynamic (PD) reasoning, compound-target engagement, causal target validation, developability and safety, and translational efficacy. Agents receive realistic workflow snapshots, inspect files in a coding environment, and return structured answers graded deterministically. Across 16 model-harness configurations, comprising 11 models and 4,800 trajectories, no system reliably recovered preclinical pharmacology decisions. The strongest configu
We study the problem of estimating locations in time at which the level of technology in an economy changes when given a sequence of time ordered inputs and outputs. We approach the problem through the lens of nonparametric frontier analysis with frontiers that expand sharply and globally over time, and develop an offline change point detection procedure which achieves the minimax localization rates for the problem at hand up to logarithmic factors. We additionally give a simple method for constructing confidence intervals for the unobserved change point locations. Finally, we explain how the procedure can be modified to accommodate local changes in technology, meaning that efficiency gains are only realized for certain combinations of inputs. Simulation studies and real data examples are also presented to illustrate the practical value of our methods.
A fundamental mistake in receptor theory has led to an enduring misunderstanding of how to estimate the affinity and efficacy of an agonist. These properties are inextricably linked and cannot be easily separated in any case where the binding of a ligand induces a conformation change in its receptor. Consequently, binding curves and concentration-response relationships for receptor agonists have no straightforward interpretation. This problem, the affinity-efficacy problem, remains overlooked and misunderstood despite it being recognised in 1987. To avoid the further propagation of this misunderstanding, we propose that the affinity-efficacy problem should be included in the core curricula for pharmacology undergraduates proposed by the British Pharmacological Society and IUPHAR.
Metabolic diseases such as type 2 diabetes and obesity represent a rapidly escalating global health burden, yet current therapeutic strategies largely target isolated symptoms or single molecular pathways. To this end, we developed an integrated computational pipeline leveraging knowledge graph, pathway analysis and network pharmacology to elucidate the multi-target mechanisms of Ayurvedic Single Herbal Drugs (SHDs). SHDs associated with diabetes and obesity were curated from the Ayurvedic Pharmacopoeia of India, followed by phytochemical identification using IMPPAT database, yielding a shortlist of 11 SHDs and their 188 phytochemicals after drug-likeness and bioavailability filtering. Subsequently, molecular targets of the phytochemicals in SHDs, disease-associated genes and therapeutic targets of FDA-approved drugs, were curated via integration of data from several databases. Pathway enrichment analysis revealed significant functional overlap between SHD-associated and disease-associated pathways. All curated data were embedded into a Neo4j-based knowledge graph, enabling SHD-disease intersection analysis that prioritized key disease-relevant targets, including PTPN1, GLP1R, and
Robotic exploration in large-scale environments is computationally demanding due to the high overhead of processing extensive frontiers. This article presents an OctoMap-based frontier exploration algorithm with predictable, asymptotically bounded performance. Unlike conventional methods whose complexity scales with environment size, our approach maintains a complexity of $\mathcal{O}(|\mathcal{F}|)$, where $|\mathcal{F}|$ is the number of frontiers. This is achieved through strategic forward and inverse sensor modeling, which enables approximate yet efficient frontier detection and maintenance. To further enhance performance, we integrate a Bayesian regressor to estimate information gain, circumventing the need to explicitly count unknown voxels when prioritizing viewpoints. Simulations show the proposed method is more computationally efficient than the existing OctoMap-based methods and achieves computational efficiency comparable to baselines that are independent of OctoMap. Specifically, the Bayesian-enhanced framework achieves up to a $54\%$ improvement in total exploration time compared to standard deterministic frontier-based baselines across varying spatial scales, while gu
Defining interdisciplinary physics today requires first a reformulation of what is physics today, which in turn calls for clarifying what makes a physicist. This assessment results from my forty year journey arguing and fighting to build sociophysics. My view on interdisciplinary physics has thus evolved jumping repeatedly to opposite directions before settling down to the following claim: today physics is what is done by physicists who handle a problem the "physicist's way". However the training of physicists should stay restricted to inert matter. Yet adding a focus on the universality of the physicist approach as a generic path to investigate a topic. Consequently, interdisciplinary physics should become a cabinet of curiosities including an incubator. The cabinet of curiosities would welcome all one shots papers related to any kind of object provided it is co-authored at least by one physicist. Otherwise the paper should uses explicitly technics from physics. In case a topic gets many papers, it would be moved to the incubator to foster the potential emergence of a new appropriate subfield of physics. A process illustrated by the subsection social physics in Frontiers in physic
Objective: The study explored therapeutic targets and mechanisms of Gegen Qinlian Decoction for Helicobacter pylori infection and related gastric cancer using network pharmacology, molecular docking, and Mendelian randomization. Methods: Medicinal components of Gegen Qinlian Decoction were extracted from TCMSP and HERB databases. Disease treatment targets were sourced from DisGeNET and PubChem. Interaction networks were constructed via the STRING database and visualized using Cytoscape 3.9.1. Enrichment analysis of intersected targets was performed using DAVID and Metascapes. Molecular docking employed Autodock Tools 1.5.6 and PyMOL 2.5.2. Mendelian randomization was based on the ukb-b-531 sample from UK Biobank. Results: 146 active components and 248 targets from Gegen Qinlian Decoction were identified. 66 targets overlapped with Helicobacter pylori infection genes. Molecular docking highlighted interactions between primary drug components like quercetin, wogonin, kaempferol, and target genes PTGS1, PTGS2, MAPK14. Mendelian randomization pinpointed genes like IGF2, PIK3CG, GJA1, and PLAU associated with Helicobacter pylori infection. Conclusion: Gegen Qinlian Decoction's active co
Natural language processing (NLP) is an area of artificial intelligence that applies information technologies to process the human language, understand it to a certain degree, and use it in various applications. This area has rapidly developed in the last few years and now employs modern variants of deep neural networks to extract relevant patterns from large text corpora. The main objective of this work is to survey the recent use of NLP in the field of pharmacology. As our work shows, NLP is a highly relevant information extraction and processing approach for pharmacology. It has been used extensively, from intelligent searches through thousands of medical documents to finding traces of adversarial drug interactions in social media. We split our coverage into five categories to survey modern NLP methodology, commonly addressed tasks, relevant textual data, knowledge bases, and useful programming libraries. We split each of the five categories into appropriate subcategories, describe their main properties and ideas, and summarize them in a tabular form. The resulting survey presents a comprehensive overview of the area, useful to practitioners and interested observers.