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01.
arXiv (CS.LG) 2026-06-24

Natural Identifiers for Privacy and Data Audits in Large Language Models

arXiv:2606.24408v1 Announce Type: new Abstract: Assessing the privacy of large language models (LLMs) presents significant challenges. In particular, most existing methods for auditing differential privacy require the insertion of specially crafted canary data during training, making them impractical for auditing already-trained models without costly retraining. Additionally, dataset inference, which audits whether a suspect dataset was used to train a model, is infeasible without access to a private non-member held-out dataset. Yet, such held-out datasets are often unavailable or difficult to construct for real-world cases since they have to be from the same distribution (IID) as the suspect data. These limitations severely hinder the ability to conduct scalable, post-hoc audits. To enable such audits, this work introduces natural identifiers (NIDs) as a novel solution to the above-mentioned challenges. NIDs are structured random strings, such as cryptographic hashes and shortened URLs, naturally occurring in common LLM training datasets. Their format enables the generation of unlimited additional random strings from the same distribution, which can act as alternative canaries for audits and as same-distribution held-out data for dataset inference. Our evaluation highlights that indeed, using NIDs, we can facilitate post-hoc differential privacy auditing without any retraining and enable dataset inference for any suspect dataset containing NIDs without the need for a private non-member held-out dataset.

02.
Nature (Science) 2026-06-09

Good recycling starts at home — and benefits the world

Authors: Unknown Author

New research supports the value of household-level waste separation. But policies must also carefully consider consumer behaviours to maximize the quality of material collected. New research supports the value of household-level waste separation. But policies must also carefully consider consumer behaviours to maximize the quality of material collected.

03.
arXiv (CS.AI) 2026-06-16

Metric Match: A Subset Selection Approach to Evaluating LLM Judge Reliability

arXiv:2606.15029v1 Announce Type: new Abstract: LLM judges are used to reduce the need for costly human labor in evaluating open-ended text generation. However, the reliability of these judges depends critically on their alignment with human raters – a property that itself depends on costly human annotations. In this work, we develop a method (Metric Match) for estimating correlation-based reliability metrics of LLM judges from limited annotations. Metric Match selects a subset of samples for human annotation such that the subset matches the population reliability metric with respect to acquired synthetic labels. We empirically show that Metric Match achieves a win-rate of 0.838 against random subset selection across four different correlation metrics and 15 datasets, with an 18.7% decrease in average estimation error and reduces annotation needs by 32.5%. We provide a cost model and highlight a medical case study where our method saves $1,041.67 compared to random selection for expert annotation. Further, we shift our task from reliability estimation to reliability classification of whether a given judge is above a deployment threshold, outperforming random selection with Metric Match. All project code is publicly available, and we additionally provide an installable package for ease of use.

04.
arXiv (CS.AI) 2026-06-15

Active Inference for Adaptive Traffic Signal Control in Noisy Nonstationary IoT Environments

arXiv:2606.13698v1 Announce Type: cross Abstract: Urban traffic signal control at IoT-instrumented intersections must remain effective under sensor occlusion, weather attenuation, and nonstationary demand. Conventional controllers degrade under these conditions, and learned policies remain difficult to audit. To address these challenges, we propose an active inference controller for a four-arm signalized intersection that dynamically selects phases by minimizing expected free energy (EFE) over Gaussian beliefs about per-direction congestion levels, yielding a fully traceable decision pipeline. We benchmark the controller in a SUMO traffic simulator against a rule-based heuristic and a deep Q-network (DQN) across four scenarios that progressively increase noise and nonstationarity, spanning sensor occlusion, adverse weather, and stochastic accidents. Across 100 independent random evaluations per scenario, active inference attains the lowest idle times and CO2 emissions in the noisiest scenarios (56,977 s and 29.12 kg vs. 71,741 s and 30.56 kg for DQN). These gains come at a modest cost in bus priority service rate and phase switch frequency.

05.
arXiv (math.PR) 2026-06-16

A uniform-in-time weakly convergent explicit numerical method for the underdamped Langevin equation with polynomial potentials

Authors:

arXiv:2606.15175v1 Announce Type: cross Abstract: The underdamped Langevin equation is a fundamental model in statistical mechanics for sampling Gibbs measures and simulating molecular dynamics, for which numerical methods with uniform-in-time weak convergence are essential for accurately reproducing long-time statistical observables and invariant measures of the underlying dynamics. Currently, such uniform-in-time weak convergence is established for implicit schemes, but remains unknown for explicit ones under polynomially growing potentials. To improve efficiency in long-time simulations, we propose the first explicit numerical method for the underdamped Langevin equation with polynomially growing potentials that is proven to achieve uniform-in-time weak convergence. The explicit numerical method is constructed by introducing a dissipativity on the scalar auxiliary variable (SAV), which we call the DSAV method. The proposed DSAV method enables the approximation of the invariant measure for the underdamped Langevin equation with a precision of $\varepsilon$ at a significantly reduced computational cost of $\mathcal{O}(\varepsilon^{-1} \log(\varepsilon^{-1}))$. In addition, we establish the existence and positivity of the density function of the numerical solution without using the Malliavin calculus. Numerical experiments are performed to verify the theoretical findings and demonstrate the long-time stability of the proposed numerical method.

06.
arXiv (CS.CL) 2026-06-12

AfriSUD: A Dependency Treebank Collection for Evaluating Models on African Languages

Despite their linguistic diversity and global significance, African languages remain underrepresented in research and resources to support NLP. We aim to bridge this gap by introducing AfriSUD, the first large-scale collection of syntactically annotated treebanks for nine diverse African languages spanning major language families and regions across Sub-Saharan Africa. Using the Surface-Syntactic Universal Dependencies (SUD) framework, our community-led effort provides high-quality, native-speaker verified data that capture typological key features such as agglutination and tone. We evaluate a range of models on AfriSUD for part-of-speech tagging and dependency parsing including non-transformer baselines, multilingual pretrained encoders, and LLMs. Our results reveal a significant syntax gap, where models still show clear limitations across the nine languages, suggesting that existing architectures may not fully capture the structural diversity of African-language syntax.

07.
arXiv (CS.CL) 2026-06-24

SURGELLM: Rethinking Multi-Task Evaluation through Task-Aware Feature Gating with Class-Balanced Normalization

Fine-tuned encoders deployed across heterogeneous NLP tasks face three compounding problems: mismatched inductive biases, class-imbalance corruption of feature statistics, and no mechanism to condition attention on external lexical knowledge. We introduce \surgellm, a unified transformer framework that addresses each with a dedicated lightweight module: a surgical feature gate (learned per-dimension sigmoid over curated lexical indicators and \texttt{[CLS]}; provably degenerates to identity when features are uninformative), task-conditioned prefix tokens (quantized feature values and task identity prepended to every input), and Instance-Weighted Normalization (IWN; removes class-prior bias from gate statistics). We prove an excess-risk bound linking gate benefit to surgical feature alignment. Across four tasks, SST-2, multi-hop retrieval, LLM-prompt attribution, and authorship detection, covering 17,830 examples and eleven model variants over three seeds, the IWN variant achieves macro-F1 0.940 ($+0.036$ over the strongest non-IWN baseline; $+0.130$ on authorship detection). A random-vocabulary control ($-0.028$ avg.\ F1) confirms gains are lexical, not parametric. Code, vocabularies, and a $99.5\%$-recovery auto-extraction recipe are released.

08.
arXiv (CS.CL) 2026-06-19

IHUBERT: Vector-Based Semantic Deduplication and Domain-Balanced Pretraining for Persian Resources

Persian pretrained language models (PLMs) are still limited by the scarcity of large-scale, high-quality pretraining corpora and by insufficient evaluation beyond standard classification and NER tasks. We present IHUBERT, a monolingual Persian PLM trained from scratch with the RoBERTa-base encoder (125M parameters) on a 45 GB curated subset of the Sepahr-Danesh collection (about 7-8B tokens). To improve corpus quality and reduce redundancy, we employ a multi-stage preprocessing pipeline that includes normalization, exact and near-duplicate removal, anonymization, and vector-database-based semantic deduplication for distribution balancing control across domains and registers. We additionally train a 139k-vocabulary BPE tokenizer on the full pretraining corpus to better capture Persian morphology and orthographic variation. IHUBERT is evaluated on seven Persian NLU benchmarks covering NER, sentiment analysis, topic classification, NLI, extractive question answering, and relation extraction, using task-standard metrics (entity-level F1, Macro-F1, EM/F1). IHUBERT achieves its strongest gains on extractive QA, ranking first on both PQuAD (F1 88.3542) and ParsiNLU-RC (F1 49.0987), and attains the best result on FarsTail (Macro-F1 0.8350). On NER and topic classification, it remains competitive (e.g., 0.8308 F1 on ParsTwiNER; 0.7953 Macro-F1 on DigiMag), while relation extraction remains the main remaining gap (0.6684 Macro-F1 on PERLEX). A controlled tokenizer ablation on the IHUBERT pretraining corpus shows that BPE yields slightly lower subword fragmentation than WordPiece at matched vocabulary size, supporting our tokenization design. Overall, IHUBERT advances Persian language modeling through semantically curated large-scale pretraining and broad evaluation across both classification and comprehension-oriented tasks.

09.
arXiv (CS.AI) 2026-06-25

OmegAMP: Targeted AMP Discovery via Biologically Informed Generation

arXiv:2504.17247v3 Announce Type: replace-cross Abstract: Deep learning-based antimicrobial peptide (AMP) discovery faces critical challenges such as limited controllability, lack of representations that efficiently model antimicrobial properties, and low experimental hit rates. To address these challenges, we introduce OmegAMP, a framework designed for reliable AMP generation with increased controllability. Its diffusion-based generative model leverages a novel conditioning mechanism to achieve fine-grained control over desired physicochemical properties and to direct generation towards specific activity profiles, including species-specific effectiveness. This is further enhanced by a biologically informed encoding space that significantly improves overall generative performance. Complementing these generative capabilities, OmegAMP leverages a novel synthetic data augmentation strategy to train classifiers for AMP filtering, drastically reducing false positive rates and thereby increasing the likelihood of experimental success. Our in silico experiments demonstrate that OmegAMP delivers state-of-the-art performance across key stages of the AMP discovery pipeline, enabling us to achieve an unprecedented success rate in wet lab experiments. We tested 25 candidate peptides, 24 of them (96%) demonstrated antimicrobial activity, proving effective even against multi-drug resistant strains. Our findings underscore OmegAMP's potential to significantly advance computational frameworks in the fight against antimicrobial resistance.

10.
arXiv (CS.CV) 2026-06-24

TIGER: Taming Identity, Geometry, and Generative Priors for High-Quality Face Video Restoration

Face Video Restoration (FVR) aims to recover high-fidelity facial videos from degraded input while preserving identity and semantic consistency across frames. Existing methods often struggle to simultaneously address three key challenges: identity shift, viewpoint-entangled guidance, and perceptual realism. To tackle these issues, we propose TIGER, a structured tri-prior fusion framework that Tames Identity, Geometry, and gEnerative pRiors for high-quality FVR. Specifically, an Identity Prior is first established by injecting subject-discriminative embeddings into the latent space, effectively anchoring the subject's identity against severe degradations. Then, to provide temporally consistent structural guidance for dynamic videos, TIGER constructs a Geometry Prior by lifting 2D reference cues into a disentangled 3D parameter space, creating a geometric anchor through cross-source parameter fusion. Moreover, to achieve maximum efficiency without compromising realism, we harness the video generation model's Generative Prior through a one-step rectified flow. We further design a progressive three-stage training optimization strategy that refines structural fidelity, textural reconstruction, and distribution-level realism to ensure robust optimization. We also construct a large-scale FVR dataset to facilitate robust training and standardized evaluation. Extensive experiments demonstrate that TIGER achieves state-of-the-art performance in both identity fidelity and temporal stability, delivering a high-quality, efficient and identity-consistent FVR. Project page: https://yzhoulv.github.io/Tiger/.

11.
arXiv (quant-ph) 2026-06-12

Roto-Reflection Geometry of Pure Two-Qubit Entanglement

arXiv:2606.12637v1 Announce Type: new Abstract: Pure two-qubit entanglement is usually characterized by scalar quantities such as concurrence. Here we show that it also has a natural geometric form. In the Pauli correlation tensor, maximally entangled states appear as improper orthogonal maps between two local Bloch spheres. These maps are roto-reflections. For partially entangled pure states, the same roto-reflection geometry is recovered after separating the contraction associated with concurrence. We call the corresponding geometric object the Entanglement Roto-Reflection Plane (ERRP). It organizes the maximally correlated directions of the two-qubit state and provides a covariant geometric complement to the scalar magnitude of entanglement.

12.
arXiv (CS.LG) 2026-06-11

My Chemical Harness: Evolutionary Molecular Design over Synthetic Pathways with Large Language Model Agents

arXiv:2606.11256v1 Announce Type: cross Abstract: Designing molecules with target properties is most useful when candidate structures are accompanied by feasible synthetic routes. We introduce My Chemical Harness, a route-native evolutionary framework for goal-directed molecular design in which the search population consists of executable synthetic pathways rather than isolated molecular graphs. Each route is built from purchasable building blocks and reaction templates, executed by deterministic chemistry tools, and scored through task-specific molecular oracles. Large language models (LLMs) are used only as strategy controllers that select high-level preferences over route length, move type, reaction families, motifs, and exploration pressure, while local code performs route construction, validation, deduplication, scoring, selection, and memory updates. This separation lets the LLM guide exploration without allowing it to introduce hallucinated products or unsupported reaction steps. On a soluble epoxide hydrolase proxy task, our LLM agent improves over single pass LLM and deterministic controllers, reaching state-of-the-art performance across the sEH score, synthetic accessibility score, and AiZynthFinder success rate metrics. These results suggest that constrained LLM agents can play a significant role in molecular discovery without requiring training, fine-tuning, or dedicated generative models.

13.
medRxiv (Medicine) 2026-06-23

Multidimensional motivation in aging: a person-centred framework spanning goal-directed behaviour, social reward and pleasure

Motivational changes are determinants of healthy aging, social engagement, and functional independence, and may signal early neurodegenerative risk. Existing assessment approaches in aging typically treat motivation as a unitary construct. Here, we introduce MotDem, an age-appropriate measure of motivation co-designed with people living with dementia, carers, and clinicians. Across a broad adult lifespan sample (18-80 years), MotDem revealed a robust three-domain motivational architecture encompassing goal-directed behaviour, social reward, and pleasure, with a fourth satiety factor retained as exploratory. This structure was replicated in an independent older cohort (45-80 years) from a different national context. MotDem showed strong convergence with established measures of apathy and anhedonia, alongside more modest associations with depressive symptomatology. Together, these findings show that motivational aging is multifaceted and poorly captured by traditional unitary assessment. MotDem provides a multidimensional framework for measuring distinct motivational drivers of heterogeneous aging trajectories, with implications for resilience, wellbeing, and neurodegenerative risk.

14.
arXiv (quant-ph) 2026-06-19

Near-Optimal Learning of Local Lindbladians

arXiv:2606.20535v1 Announce Type: new Abstract: We study the problem of learning local Lindbladians from black-box access to the physical evolution, and the goal is to estimate all Hamiltonian and dissipative coefficients. We give an algorithm built directly from finite-time channel probes, which runs the unknown evolution for short times, estimates the corresponding Pauli transfer matrices from classical shadows, and converts these estimates into Lindbladian coefficients by stable local Fourier inversions. For fixed locality and bounded dissipative site degree, the uses of the dynamical evolution and total evolution time scale as $\widetilde{O}(\Lambda^2/\varepsilon^2)$ and $\widetilde{O}(\Lambda/\varepsilon^2)$ respectively, in the local dynamical strength bound $\Lambda$ and target accuracy $\varepsilon$, with only logarithmic dependence on the number of qubits. The algorithm is non-adaptive, uses no ancillas, and uses only random product states as inputs followed by random Pauli measurements. The method does not require knowing the support of the Lindbladian in advance. We complement the algorithm with matching lower bounds, showing that the learning algorithm is near-optimal both in physical dynamics accesses and in total evolution time. We construct a single-qubit dephasing Lindbladian family that already requires $\Omega(\Lambda^2/\varepsilon^2)$ channel uses and $\Omega(\Lambda/\varepsilon^2)$ total evolution time, even for adaptive algorithms with arbitrary ancillas and measurements. In particular, the lower bounds imply that the Heisenberg-limited scaling achievable for Hamiltonian learning is information-theoretically impossible once dissipative coefficients must be estimated.

16.
arXiv (CS.CV) 2026-06-16

Projection and Quantisation: A Unifying View of Learning to Hash, from Random Projections to the RAG Era

Authors:

Approximate nearest-neighbour search underpins large-scale retrieval and retrieval-augmented generation, yet its methods are studied in communities that seldom read one another. We argue that they form one field with three design choices. We develop the projection-quantisation-organisation lens: every method places its projections, places its quantisation thresholds, and organises the resulting codes for search. We test the lens with a reproducible measurement, released as the open BitBudget benchmark, and report three findings. First, the quantisation axis delivers the largest memory savings: a one-bit code with full-precision re-ranking matches uncompressed quality for six of seven embedders, the scanned code one thirty-second of the float's size. Second, the orderings the lens anticipates, including a learned-embedding regime where binary codes overtake an inverted-file product quantiser at a matched byte budget, recur as the embedding is enlarged. Third, given class labels, an eight-byte supervised code more than doubles the retrieval quality of the two-kilobyte task-agnostic float it replaces. We also recast the semantic identifiers of generative retrieval as quantisation codes. The main contribution is a single, tested account of compact-code search, from random projections to the retrieval-augmented era.

17.
arXiv (CS.AI) 2026-06-16

MiroBench: Benchmarking Realism in Agentic Simulation of Real-world Discussions

arXiv:2606.14715v1 Announce Type: cross Abstract: LLM agents are increasingly used to simulate real world interactions, but it remains unclear whether simulated behaviors preserve the content patterns and interaction dynamics of real human behaviors. Existing evaluations remain fragmented, which makes it difficult to compare systems or measure progress. In this paper, we focus on Reddit discussions as a concrete first step toward evaluating real-world social simulation. Reddit threads provide public, topic-grounded, multi-party interactions where people share experiences, debate, seek advice, express emotion, and collectively respond to products, events, and social issues. These discussions offer an observable window into broader social behavior, making them a useful setting for testing whether LLM agents can reproduce not only fluent text, but also the distributional patterns and interaction dynamics of real online communities. We introduce MiroBench, a benchmark for Reddit discussion simulation built from 4,292 real Reddit threads. MiroBench uses statistical tests to compare generated and real discussions across four major aspects: repetition and semantic uniformity, narrative content, toxicity and aggression, and structural complexity. Experiments across five domains and five models show that current simulators remain distributionally mismatched with real Reddit threads, while a lightweight prompt-based improvement procedure provides only limited gains. MiroBench offers a concrete benchmark for measuring, diagnosing, and improving realism in LLM-based social simulation.

18.
arXiv (math.PR) 2026-06-12

Scaling limits of the single-curve interface and outermost loops in the planar random field Ising model

arXiv:2606.13147v1 Announce Type: new Abstract: We prove that the interface separating $+1$ and $-1$ spins in the near-critical planar random field Ising model (RFIM) with Dobrushin boundary conditions has a scaling limit, whose law is conformally covariant and almost surely absolutely continuous with respect to SLE$_3$. The limiting curve can be seen as a massive version of SLE$_3$ in the sense of Makarov and Smirnov, but in a random environment. We then show that the outermost spin loops of the near-critical planar RFIM with $+1$ boundary conditions have subsequential limits and that any of these limits is almost surely singular with respect to CLE$_3$. This dichotomy between absolute continuity of the single interface and singularity of the outermost loops reflects the fact that a single interface does not explore enough of the magnetization field of the near-critical RFIM to detect the singularity of this field with respect to the critical Ising magnetization field, whereas the outermost spin loops do.

19.
arXiv (CS.CV) 2026-06-12

VietFashion: Benchmarking Sketch-Text Composed Image Retrieval for Cultural Outfits

Cultural garments pose a unique challenge for visual retrieval systems, as their identity often depends on subtle structural and symbolic details that are poorly captured by standard AI models. We introduce VietFashion, a new benchmark for sketch-text composed image retrieval centered on the Ao Dai, a traditional Vietnamese garment. VietFashion enables designers and researchers to retrieve culturally meaningful outfits using a combination of hand-drawn sketches, which convey garment structure, and textual descriptions, which encode cultural semantics. The dataset is initialized with 650 sketches and expanded using generative models to produce over 21,000 photorealistic images with aligned captions. Textual prompts that describe detailed outfit attributes, which are extracted from fashion magazines to ensure authenticity and diversity. To better reflect the inherent ambiguity of design intent, VietFashion adopts a multi-target retrieval setting, where a single query may correspond to multiple valid results. We establish standardized evaluation protocols and benchmark state-of-the-art composed image retrieval methods. Experimental results reveal significant performance gaps in modeling fine-grained cultural semantics and multi-modal composition, positioning VietFashion as a challenging benchmark for fine-grained fashion retrieval. The dataset is publicly available at: https://hng0303.github.io/VietFashion.

20.
arXiv (CS.AI) 2026-06-25

AI Coaching for Accelerating Human Skill Development with Reinforcement Learning

arXiv:2606.25337v1 Announce Type: cross Abstract: AI copilots can substantially boost human performance through shared control, but excessive assistance can induce over-reliance and skill atrophy. This paper studies how an embodied AI agent can act as a coach that accelerates human motor-skill development. We argue that effective coaching requires strategic scaffolding and stepping back that are aligned with the learner's capability, allowing productive failures that drive learning. We formalize the interactive AI coaching process as a non-cooperative dynamic game in which the learner optimizes task performance while the coach targets the learner's independent competence. Building on this formalism, we develop a reinforcement learning framework combining adaptive shared control with probabilistic models of the coach's causal influence on skill evolution, enabling tractable training of coaching policies. A comprehensive user study (N=33) on first-person-view drone racing shows significant gains in human learning outcomes over state-of-the-art AI coaching baselines.

21.
arXiv (CS.LG) 2026-06-12

Circuit Synchronization Precedes Generalization: Causal Evidence from Fourier Structure in Grokking Transformers

arXiv:2606.12966v1 Announce Type: new Abstract: Grokking – where a transformer on modular arithmetic suddenly transitions from near-chance to near-perfect validation accuracy – is attributed to a Fourier circuit, but its timing, causal structure, and controllability remain poorly understood. We introduce the Frequency Synchronization Degree (FSD), a normalised, permutation-tested metric for Fourier circuit synchronisation requiring no prior circuit knowledge. Across nine modular addition configurations (primes p in {53, 71, 97, 113, 131}, three seeds), FSD synchronises 500-3,000 steps before grokking (mean lead +1,722 steps; all nine positive, sign-test p~0.004), and precedes a restricted-logit loss baseline (Nanda et al.'s excluded loss) in all nine cases, making it the earliest available predictor. We provide direct causal evidence that the inter-phase gap is a regularisation phenomenon: forking training at the FSD-ceiling step and varying weight decay lambda produces strictly monotone earlier grokking, with Delta_t proportional to 1/lambda. This law replicates across three primes (p in {53,97,131}; R^2=1.00 and R^2=0.99 for two clean cases), captured as Delta_t ~ C/lambda, consistent with (1/lambda)*log(||W_mem||/tau). Architecture ablations show an attention-only model groks with a strong FSD precursor; an MLP-only model never groks; a single-layer model's FSD lags, confirming the precursor is a multi-block circuit property.

22.
arXiv (CS.LG) 2026-06-11

Neural-Parameterized Cellular Automata for Wildfire Spread

arXiv:2606.11676v1 Announce Type: cross Abstract: Traditional wildfire models rely on rigid, low-dimensional parameters and static fuel maps, frequently underpredicting fire spread. To address this weakness, we introduce a hybrid deep-learning parameterized Probabilistic Cellular Automata (CA) framework implemented in JAX. Our approach employs a Multi-Scale Convolutional Neural Network to dynamically generate spatially varying parameters that govern fire-spread probability, wind alignment, and slope influence. This hybrid design captures complex, nonlinear environmental interactions while preserving the physical interpretability of the underlying three-state CA. The JAX implementation enables hardware acceleration and gradient-based parameter calibration. Evaluated on six large-scale wildfires in the western United States, the model maintains IoU > 0.6 over 72-hour forecast horizons after a 10-day data assimilation window during which the model is fitted incrementally to observed perimeters; the resulting forecast is a conditional projection of fire growth under the suppression regime already ncoded in those observations.

23.
bioRxiv (Bioinfo) 2026-06-12

From Proteome Mining to Structural Validation: Phosphopyruvate Hydratase as a Structurally Tractable Drug Target in Kinetoplastid Parasites

Chagas disease, caused by Trypanosoma cruzi, demands novel therapeutic strategies that overcome the toxicity and limited efficacy of current treatments. To address this need, herein we report an integrative, target-centric strategy that combines parasite proteome mining, structural modeling, and experimental validation. Functional enrichment and druggability analyses identified phosphopyruvate hydratase (PPH) as a promising candidate due to its essential metabolic role and limited similarity to human homologs. Notably, proteome mining revealed the presence and conservation of PPH across kinetoplastid parasites, including Leishmania donovani, supporting its evaluation beyond T. cruzi. For the selected PPH sequences, AlphaFold-derived three-dimensional models underwent extensive molecular dynamics refinement, yielding stable conformational ensembles suitable for structure-based studies. Using this validated model, virtual screening of the Latin American Natural Products Database - LANaPDB - identified aptosimon as a top-ranked compound candidate. Molecular dynamics simulations further showed ligand-dependent binding behavior, suggesting alternative binding modes distinct from the canonical substrate configuration. In vitro assays demonstrated consistent antiparasitic activity against intracellular T. cruzi amastigotes (IC50 = 3.52 ug/mL) and Leishmania donovani promastigotes (IC50 = 13.06 ug/mL), supporting the biological relevance of the aptosimon-related lignan chemotype, hinokinin, across two kinetoplastid parasite models. Together, these results support PPH as a structurally tractable and biologically relevant candidate target, while identifying an aptosimon-related lignan chemotype, represented experimentally by hinokinin, as a cross-species antiparasitic scaffold that warrants further biochemical target-validation studies.

24.
bioRxiv (Bioinfo) 2026-06-16

Phylogenetic tree inference using generative models

Accurate inference of phylogenetic trees is fundamental to evolutionary biology, yet existing methods rely on complex pipelines involving multiple sequence alignment, explicit evolutionary models, and computationally intensive tree search procedures. Here, we present BetaInfer, a generative framework that reformulates phylogenetic tree inference as a sequence transduction problem. BetaInfer leverages hybrid transformer-based architectures to directly map sets of unaligned sequences to phylogenetic trees represented in Newick format. Trained on large-scale simulated evolutionary data with known ground truth, BetaInfer learns to capture complex evolutionary signals directly from sequence data. Ensemble-based generation of multiple candidate trees further improves robustness, reducing reconstruction error by over 30% relative to single predictions. Across extensive evaluations on both simulated and empirical datasets, BetaInfer achieves competitive performance relative to state-of-the-art phylogenetic pipelines, matching, and in some cases exceeding, the accuracy of established likelihood-based and distance-based methods under a wide range of conditions. Interpretability analyses reveal that BetaInfer leverages internal pairwise-distance computations to synthesize evolutionary relationships into an integrated, global representation that supports direct tree generation. Together, these results demonstrate that generative models can serve as a viable and scalable alternative to standard phylogenetic pipelines.

25.
arXiv (CS.LG) 2026-06-15

A Low-Rank Subspace Analysis of LLM Interventions

arXiv:2606.14388v1 Announce Type: new Abstract: Interventions designed to modify a particular behavior in LLMs, such as refusal or sycophancy, often produce unintended changes in other behaviors. This lack of targeted control makes it difficult to design and implement reliable safety controls. To understand these side-effects, we introduce a diagnostic framework for analyzing interacting behaviors in LLMs. We model behaviors as low-rank subspaces in activation space, and study how interventions influence across behaviors. Across multiple instruction-tuned models (7B-70B) and across refusal, jailbreak, and sycophancy settings, we find that different behaviors share internal representations, and intervening on one behavior alters others in asymmetric ways. Some behaviors act as upstream control points whose interventions propagate broadly across other behaviors, while others remain more isolated. We relate these effects to two geometric quantities: (i) the overlap between behavior subspaces, measured as the average squared cosine of principal angles, and (ii) the angle between each behavior subspace and the decision subspace (capturing the model's final decision e.g., refuse vs. comply). Empirically, intervention effects on other behaviors tend to be larger for behavior pairs with higher subspace overlap, and for source behaviors whose subspaces lie closer (smaller angle) to the decision subspace. These findings highlight a challenge for targeted behavior control: behaviors are difficult to modify independently, as interventions can propagate through shared representations and asymmetric interactions.