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01.
arXiv (CS.LG) 2026-06-16

Graphical conditional generative modeling for digital twin modeling

arXiv:2606.16219v1 Announce Type: cross Abstract: Digital twin modeling, including control and data assimilation under model uncertainty, often faces an open-ended fidelity problem: adding variables, data streams, and time scales can indefinitely increase model complexity, ultimately producing systems that are difficult to maintain, validate, interpret, and use for stress or safety testing. As an alternative, one can seek parsimonious stochastic surrogate models built only on the variables needed to describe the relevant quantities of interest. We introduce a framework for discovering such variables from observational data by identifying which candidate inputs influence the full conditional law of a target quantity, rather than only its conditional mean. This distinction is essential in stochastic, coarse-grained, or partially observed systems, where dependencies may appear through changes in variability, tail behavior, multimodality, or uncertainty rather than through deterministic functional relationships. The framework couples conditional generative modeling, which learns the conditional distribution of the target given candidate inputs, with Gaussian-process-based analysis of variance (through kernel mode decomposition), which enables iterative pruning of non-influential inputs and interpretable structure discovery. In control settings, the resulting surrogate can be interpreted as a learned Markov decision process: the method identifies not only a transition model, but also the state, action, and memory variables needed to make the learned dynamics effectively Markovian. Across examples involving stochastic dynamical systems, missing variables, PDE control, reinforcement learning, and economic data, the discovered structures yield interpretable stochastic surrogates whose downstream performance is comparable to models trained on the full variable set.

03.
arXiv (CS.AI) 2026-06-18

Optimizing Lithium Production Decisions under Geological, Demand, and Pricing Uncertainties: A POMDP Framework for Multi-Objective Decision Making

arXiv:2606.18598v1 Announce Type: new Abstract: Decision making in lithium production is challenging, whether from an investor's perspective or a strategic production standpoint. Determining which mines to open and when to open them involves not only geological and price uncertainties, but also complexities around the choice of extraction method, from direct lithium extraction to hard rock mining. Prior work explored models of this problem and different methods to optimize mining decisions; these models did not account for uncertainty in pricing, uncertainty in demand, or different mining technologies to extract lithium. Incorporating different pricing models and extraction technology into these models enables more robust strategies for determining not only when and where to open a mine, but also which method of production to pursue. We frame the problem as a partially observable Markov decision process (POMDP) and solve using belief state planning methods to get optimal decision making. In our study, we show that POMDP solvers outperform human inspired heuristics by dynamically adapting to shifting lithium price regimes (static, linear, exponential, and stochastic) through belief state planning and explicit uncertainty management. By optimally sequencing exploration, production, and technology choice, the framework achieves higher demand fulfillment and more balanced economic environmental outcomes over the projects lifetime in all different pricing and deposit scenarios.

04.
Science (Express) 2026-05-28

A Hormone Cell Atlas maps the human endocrine system at cellular resolution | Science

Authors: Unknown Author

Hormones act across tissues and organs to coordinate physiological functions. Drawing inspiration from the Human Cell Atlas, we analyzed expression of 379 hormone and receptor genes in a transcriptomic dataset comprising 14 million single cells and nuclei across 47 human tissues. Using hormone2cell, we mapped putative hormone-producing and hormone-receiving cell types, defining tissue-specific and cross-tissue endocrine signatures. We predicted non-classical sites of hormone expression, including secretin in plasmacytoid dendritic cells, inferred convergent hormone action and endocrine feedback loops, and implicated cell populations in monogenic endocrine disorders. In a cross-tissue integration of adipocyte datasets, we uncovered dynamic endocrine programs across depots, within adipocyte subtypes and through adipogenic differentiation. Cumulatively, the Hormone Cell Atlas ( hormonecellatlas.org.uk ) provides a comprehensive framework for dissecting hormonal impact on health and disease.

05.
arXiv (CS.AI) 2026-06-12

HD-Prot: A Protein Language Model for Joint Sequence-Structure Modeling with Continuous Structure Tokens

arXiv:2512.15133v3 Announce Type: replace-cross Abstract: Proteins inherently possess a consistent sequence-structure duality. The abundance of protein sequence data, which can be readily represented as discrete tokens, has driven fruitful developments in protein language models (pLMs). A key remaining challenge, however, is how to effectively integrate continuous structural knowledge into pLMs. Current methods often discretize protein structures to accommodate the language modeling framework, which inevitably results in the loss of fine-grained information and limits the performance potential of multimodal pLMs. In this paper, we argue that such concerns can be circumvented: a sequence-based pLM can be extended to incorporate the structure modality through continuous tokens, i.e., high-fidelity protein structure latents that avoid vector quantization. Specifically, we propose a hybrid diffusion protein language model, HD-Prot, which embeds a continuous-valued diffusion head atop a discrete pLM, enabling seamless operation with both discrete and continuous tokens for joint sequence-structure modeling. It captures inter-token dependencies across modalities through a unified absorbing diffusion process, and estimates per-token distributions via categorical prediction for sequences and continuous diffusion for structures. Extensive results demonstrate that HD-Prot achieves competitive performance in unconditional sequence-structure co-generation, motif-scaffolding, protein structure prediction, and inverse folding tasks. Furthermore, our method can perform on par with state-of-the-art multimodal pLMs, despite being developed under limited computational resources (i.e., less than one-tenth the budget for modality extension fine-tuning). It highlights the viability of simultaneously estimating categorical and continuous distributions within a unified language model architecture, offering a promising alternative direction for multimodal pLMs.

06.
Nature (Science) 2026-06-24

Zero-shot design of drug-binding proteins via neural iterative selection−expansion

Authors:

The design of proteins that bind to small molecules has been challenging because it requires simultaneous optimization of the protein sequence, protein structure and ligand conformation1–7. Current deep-learning algorithms have struggled to navigate this landscape, precluding the zero-shot design of binders. Here we show that by combining two neural networks in an iterative design algorithm, small-molecule binding proteins can be created from scratch with high accuracy. We trained a graph neural network—ligand-aware sequence engineering message-passing neural network (LASErMPNN)—to design compatible protein sequences for an input protein backbone and docked ligand. We paired  LASErMPNN with a structure predictor that models a three-dimensional protein–ligand complex for an input protein sequence and ligand identity. The closed-loop iteration of these reciprocal networks optimized sequence–structure–ligand compatibility, and outperformed a comparable design loop using a physics-based energy function. We used our strategy, termed neural iterative selection–expansion (NISE), to design proteins that, using different folds, specifically bind to two chemically distinct small-molecule drugs, exatecan and apixaban, with success rates of 100% and 83%, respectively. The tightest NISE binders had nanomolar-to-picomolar affinities, surpassing those of the next-leading method by 70-fold for exatecan and nearly 10,000-fold for apixaban. LASErMPNN then suggested two amino-acid substitutions that improved the affinity of the tightest exatecan binder by 100-fold without any experimental input. The optimized binder protected the labile lactone ring of exatecan from hydrolysis for days. Our work describes a general recipe for using neural networks to automate the design of small-molecule binding proteins for applications in drug delivery, sensing and catalysis.  By pairing two neural networks in an iterative optimization algorithm, small-molecule binding proteins can be designed from scratch with high accuracy, affinity and success rates, showing promise for applications in drug delivery and sequestration.

07.
arXiv (CS.CL) 2026-06-11

ProcessThinker: Enhancing Multi-modal Large Language Models Reasoning via Rollout-based Process Reward

Visual question answering increasingly requires multi-step reasoning. Recent post-training with reinforcement learning under verifiable rewards (RLVR) and Group Relative Policy Optimization (GRPO) can improve multimodal reasoning, but most approaches rely on sparse outcome-only rewards. As a result, they struggle to tell whether an incorrect answer comes from a small mistake late in the reasoning or from an unhelpful trajectory from the start. A common solution is to train a process reward model (PRM) for step-level supervision, but this typically requires large-scale high-quality chain-of-thought annotations and additional training cost. We propose ProcessThinker, a practical post-training pipeline that provides step-level process rewards without training an explicit PRM. ProcessThinker first rewrites reasoning traces into a step-tagged format for cold-start supervised fine-tuning, then applies GRPO with a standard format reward and our rollout-based process reward. Concretely, for each intermediate step, we sample multiple continuations from that step and use the empirical success rate (final-answer verification) as the step reward. This gives dense credit assignment and encourages reasoning steps that more reliably support a correct conclusion, helping reduce inconsistent or self-contradictory progress across steps – a key issue in logical reasoning. Across four challenging video benchmarks (Video-MMMU, MMVU, VideoMathQA, and LongVideoBench), ProcessThinker consistently improves over the baseline model Qwen3-VL-8B-Instruct

08.
arXiv (CS.AI) 2026-06-16

Learning Interface Breakup: A Geometry-Conditioned Latent Surrogate for Spray Formation

arXiv:2606.16587v1 Announce Type: cross Abstract: Designing spray nozzles requires predicting how geometry shapes transient two-phase breakup, but high-fidelity volume-of-fluid (VOF) simulations with adaptive mesh refinement (AMR) are too expensive for iterative design exploration. Standard surrogate models are also challenged by this setting because both the liquid–gas interface and the underlying adaptive discretization evolve across time and geometries. We introduce a geometry-conditioned latent surrogate trained on 797 two-phase nozzle simulations that addresses this by encoding the AMR cell-density field, rather than the full multi-channel flow state, as a compact proxy for where the solver concentrates resolution. From this representation, the model reconstructs transient density evolution and nozzle geometry, and a lightweight second stage recovers the remaining flow variables. On held-out simulations, the method accurately captures key interface dynamics while reducing inference time to 0.045 seconds per trajectory, corresponding to a speed-up of more than $6\times10^4$ relative to Basilisk CFD. These results suggest that AMR refinement structure can serve as a compact and learnable representation for geometry-conditioned surrogate modeling of transient two-phase flows.

09.
arXiv (CS.CL) 2026-06-18

Speech-Driven End-to-End Language Discrimination towards Chinese Dialects

Language discrimination among similar languages, varieties, and dialects is a challenging natural language processing task. The traditional text-driven focus leads to poor results. In this paper, we explore the effectiveness of speech-driven features towards language discrimination among Chinese dialects. First, we systematically explore the appropriateness of speech-driven MFCC features towards CNN-based language discrimination. Then, we design an end-to-end speech recognition model based on HMM-DNN to predict Chinese dialect words. We adopt attention to extract the discriminative words related to different Chinese dialects. Finally, through a CNN, we combine the word-level embedding and the MFCC-based features. Evaluation of two benchmark Chinese dialect corpora shows the appropriateness and effectiveness of the proposed speech-driven approach to fine-grained Chinese dialect discrimination compared to the state-of-the-art methods.

10.
arXiv (quant-ph) 2026-06-19

Entanglement Scaling and Problem Structure in Quantum Approximate and Adiabatic Optimization Algorithms

arXiv:2606.19502v1 Announce Type: new Abstract: Entanglement is widely regarded as a key resource underlying the power of quantum algorithms and their potential to achieve quantum advantage. With the emergence of variational quantum algorithms, however, questions have arisen regarding how entanglement relates to problem structure and algorithmic performance in near-term quantum applications. Here, we examine this relationship through the Quantum Approximate Optimization Algorithm (QAOA), a specific class of variational algorithms, applied to the MaxCut problem. We show that suboptimal variational parameter training can significantly modify the observed entanglement profile, obscuring its scaling behavior. By employing a high-performance optimizer, we find empirical evidence that QAOA exhibits entanglement scaling consistent with that of fermionic Gaussian states (up to a scaling factor) across a broad range of MaxCut instances. We further compare these results with adiabatic quantum computation, observing annealing-schedule-dependent entanglement profiles whose scaling behavior differs markedly from that of QAOA. Together, these findings provide new insight into how entanglement manifests in and distinguishes these two algorithmic paradigms, highlighting its connection to both computational performance and application structure.

11.
arXiv (quant-ph) 2026-06-24

Perfect State Transfer on Quotient Graphs in Shunt Decomposition-Based Quantum Walks

arXiv:2606.24440v1 Announce Type: cross Abstract: This paper investigates perfect state transfer (PST) in discrete-time quantum walks constructed via the shunt decomposition method. The walks are defined on a graph $G$ and its associated quotient graph $G/\pi$, induced by an equitable partition $\pi$. Through the shunt decomposition of $G$, we derive an explicit relation between the shift operator of the parent graph $G$ and that of its quotient graph $G/\pi$. We construct a reflection operator based on the characteristic matrix, which establishes a connection between the transition operator of the parent graph and that of its lower-dimensional quotient graph. We then prove that PST occurs on $G$ if and only if it occurs on $G/\pi$. Furthermore, we express the unitary evolution operator of the quotient graph in terms of Chebyshev polynomials of the first kind, from which we derive explicit criteria for PST. As an application, we establish PST on the cycle graph $C_{n}$ at time $k = n/2$, and lift the result to the parent graph $C_{2n}$ via the equitable partition $\pi$. We further show that if an equitable partition $\pi$ of $G$ induces a quotient isomorphic to $K_n^{\circlearrowleft}$, the complete digraph on $n$ vertices with a loop at every vertex, then PST occurs at step $k = n$, and the walk is periodic at $k = 2n$. This framework is applied to two families of graphs, which are the complete bipartite digraph $K_{n,n}^{\rightleftharpoons}$ and the circulant graph $\operatorname{Circ}(2n, S)$, where $S$ consists of all odd residues modulo $2n$ and $n = 2^s$ for some $s \geq 1$, establishing PST in their respective line digraphs. Collectively, these results also answer the question posed by Godsil and Zhan concerning which shunt decompositions or embeddings of a graph admit PST.

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

Entity Binding Failures in Speech LLM Reasoning: Diagnosis and Chain-of-Thought Intervention

Speech Large Language Models (SLLMs) underperform their text counterparts on complex reasoning. We reveal that this gap is not a uniform cognitive deficit. Evaluating two architecturally diverse SLLMs, we show speech-to-text (S2T) matches or exceeds text-to-text (T2T) on spatial, syntactic, and factual tasks. Yet on logical tasks requiring entity tracking, S2T accuracy collapses to chance. We diagnose this as an entity binding failure: continuous speech features blur precise entity-property associations during implicit reasoning. To validate this diagnosis, we introduce Entity-Aware Chain-of-Thought (EA-CoT), a lightweight inference-time intervention forcing SLLMs to enumerate entities and bind them to claims before reasoning. EA-CoT bridges the gap, even when spoken names are misrecognized, yielding up to a 24.4 percentage-point accuracy gain. Ablations confirm the gains stem from explicit semantic binding, reframing the gap as an elicitation failure rather than a missing capability.

13.
arXiv (CS.AI) 2026-06-17

Dimensionality Controls When Modularity Helps in Continual Learning

arXiv:2606.17889v1 Announce Type: cross Abstract: Compositional learning systems must balance plasticity, the ability to acquire new knowledge, with stability, the preservation of previously learned components, especially when tasks share structure and risk interference. We study how modular architecture, task similarity, and representational dimensionality jointly shape compositional continual learning in a sequential A-B-A paradigm, comparing a task-partitioned recurrent network to a single-network baseline while inducing high- and low-dimensional regimes via weight-scale manipulations. In a high-dimensional "lazy" regime, both architectures achieve similar performance and internal geometry, suggesting that explicit modular structure has little impact when representations are weakly constrained. In a lower-dimensional "rich" regime, modularity becomes decisive: the modular network develops graded task-specific subspaces that overlap for similar tasks, partially align for moderately dissimilar tasks, and separate for dissimilar tasks, yielding a more compositional and interpretable organization than the single network. These findings identify the representational regime induced by initialization scale, which co-varies with representational dimensionality, as a key factor governing when compositional, modular structure is functionally beneficial in continual learning, and support viewing safety and robustness as problems of adaptive allocation of representational subspaces rather than fixed separation versus sharing.

14.
arXiv (CS.CL) 2026-06-17

Position: Coding Benchmarks Are Misaligned with Agentic Software Engineering

Coding agents have become a major mode of software engineering, but the benchmarks we use to compare them were designed in a pre-agent era: they collapse model, harness, and environment into a single end-to-end score, typically computed against one reference solution, with no component-level signal for iteration. We argue that current coding benchmarks are misaligned with agentic software engineering. A coding agent in practice is not a model: it is a system harness – a composite of models, harnesses, contexts, environments, and feedback signals, any one of which can move the benchmark score by margins comparable to those between adjacent model generations. We discuss three symptoms: (i) benchmark scores conflate the model with the rest of the harness; (ii) grading against a single reference solution penalises equally valid alternatives; and (iii) the absence of signal at the level of individual harness components makes the end-to-end system score difficult to iterate on.

15.
arXiv (CS.CV) 2026-06-19

GH-ESD: Grounded Hypothesis-Driven Error Slice Discovery for Instance-Level Vision Tasks

Systematic failures of vision models on semantically coherent subsets, known as error slices, reveal limitations in robustness and evaluation. Existing slice discovery approaches largely model slices as clusters in representation space or combinations of predefined attributes. While effective for image-level classification, such formulations are insufficient for instance-level tasks such as object detection and segmentation, where failures often arise from contextual relational and spatially grounded visual patterns. We propose GH-ESD (Grounded Hypothesis-Driven Error Slice Discovery), a generate and verify framework that reformulates slice discovery as grounded hypothesis generation and statistical verification. GH-ESD constructs relational failure hypotheses using LLM priors and grounded visual evidence, discovers hypothesis slices at the instance level via Vision Language Models, and verifies them through statistical trend analysis over instance-level errors. We also introduce GESD (Grounded Error Slice Dataset), a new benchmark for instance-level error slice discovery, providing expert-defined and spatially grounded slices derived from detection and segmentation failures. Extensive experiments demonstrate that GH-ESD consistently outperforms baselines, improving Precision@10 by 0.10 (0.73 vs. 0.63) on the GESD benchmark for detection tasks, while also supporting segmentation scenarios. GH-ESD identifies interpretable slices that facilitate actionable model improvements. The GESD dataset will be made publicly available upon acceptance.

16.
arXiv (quant-ph) 2026-06-24

Temperature driven false vacuum decay in coherently coupled Bose superfluids

arXiv:2602.03834v2 Announce Type: replace-cross Abstract: The relaxation of a quantum field from a metastable state (false vacuum) to a stable one (true vacuum), also known as false vacuum decay, is a fundamental problem in quantum field theory and cosmology. We study this phenomenon using a two-dimensional interacting and coherently coupled Bose-Bose mixture, a platform that has already been employed experimentally to investigate false vacuum decay in one dimension. In such a mixture, it is possible to define an effective magnetization that acts as a quantum field variable. Using the Stochastic Gross-Pitaevskii equation (SGPE), we prepare thermal equilibrium states in the false vacuum and extract decay rates from the magnetization dynamics. The decay rates show an exponential dependence on temperature, in line with the thermal theory of instantons. Since the SGPE is based on complex scalar fields, it also allows us to explore the behavior of the phase, which turns out to become dynamic during decay. Our results confirm the SGPE as an effective tool for studying coupled magnetization and phase dynamics and the associated instanton physics in ultracold quantum gases.

17.
arXiv (CS.AI) 2026-06-24

FP8 is All You Need (Part 2): Efficient Ozaki-Bailey Style FFT Through Tensor-core Garner Reformulation and Kulisch Escape Route

arXiv:2606.23698v1 Announce Type: cross Abstract: NVIDIA's Blackwell Ultra (B300) cuts FP64 vector throughput to ~1.3 TFLOPS per GPU, roughly 30x below B200 and well below the level at which bandwidth-limited FP64 workloads stay memory-bound. The Ozaki Scheme II framework recovers FP64-equivalent throughput by routing dense matrix multiply through FP8 tensor cores with a mantissa-sliced Chinese-remainder reconstruction. A companion Part (1) paper covers dense GEMM, batched GEMV, stencils, and SpMV; this paper adds the fifth canonical primitive, the 3-D FFT. We present Ozaki-Bailey FFT, an emulated 3-D FFT via the Bailey six-step decomposition with both 1-D FFT GEMMs on FP8 tensor cores. Bailey's small inner factor k ~ sqrt(N) (k=32 for N=1024) puts the kernel in the regime k

18.
arXiv (CS.LG) 2026-06-12

Central Limit Theorems for Stochastic Gradient Descent Quantile Estimators

arXiv:2503.02178v3 Announce Type: replace-cross Abstract: This paper develops asymptotic theory for quantile estimation via stochastic gradient descent (SGD) with a constant learning rate. The quantile loss function is neither smooth nor strongly convex. Beyond conventional perspectives and techniques, we view quantile SGD iteration as an irreducible, periodic, and positive recurrent Markov chain, which cyclically converges to its unique stationary distribution regardless of the arbitrarily fixed initialization. To derive the exact form of the stationary distribution, we analyze the structure of its characteristic function by exploiting the stationary equation. We also derive tight bounds for its moment generating function (MGF) and tail probabilities. Synthesizing the aforementioned approaches, we prove that the centered and standardized stationary distribution converges to a Gaussian distribution as the learning rate $\eta\rightarrow0$. This finding provides the first central limit theorem (CLT)-type theoretical guarantees for the quantile SGD estimator with constant learning rates. We further propose a recursive algorithm to construct confidence intervals of the estimators with statistical guarantees. Numerical studies demonstrate the effective finite-sample performance of the online estimator and inference procedure. The theoretical tools developed in this study are of independent interest for investigating general SGD algorithms formulated as Markov chains, particularly in non-strongly convex and non-smooth settings.

19.
arXiv (CS.LG) 2026-06-11

Evaluating and Combating the Impact of Concept Drift on the Performance of Machine Learning-Based Phishing Detection Systems

arXiv:2606.11471v1 Announce Type: cross Abstract: The expansion of the digital domain has resulted in a substantial increase in digital communication, with email emerging as one of the most prominent channels. The proliferation of email communication is apparent in both professional and personal contexts, thereby creating numerous vulnerabilities for malicious actors to exploit. Spam emails, a form of unsolicited correspondence often bearing malicious intent towards recipients, have been an ongoing challenge for email users since the inception of email technology, and this problem has been exacerbated by the growth of the digital landscape. Email spam filters are integral components of email clients, engineered to identify potentially harmful messages and alert users to their malicious content. Phishing, frequently the initial phase of malware-based attacks, is evolving rapidly, with malware becoming increasingly sophisticated over time. A widely adopted approach for detecting malicious activity within malware and spam domains is the application of machine learning. Our aim is to assess the impact of the evolution within the spam email domain on these machine learning-based detection systems and to explore strategies for mitigating associated performance degradation.

20.
arXiv (CS.CV) 2026-06-11

CoVEBench: Can Video Editing Models Handle Complex Instructions?

While recent text-guided video editing models excel at elementary tasks (e.g., style transfer, object insertion), real-world user requests are highly compositional. A single prompt often demands multiple coupled edits, such as modifying subjects, actions, and camera views, while strictly preserving unrelated spatiotemporal content. Existing benchmarks, heavily constrained by isolated edits and coarse global metrics, fail to diagnose how models handle such complex workflows. To address this gap, we introduce CoVEBench, a compositional video editing benchmark comprising 416 curated source videos, 626 multi-point editing instructions, and 9,990 fine-grained checklist items. Covering diverse editing dimensions, CoVEBench evaluates models via MLLM-judged instruction compliance and video fidelity, alongside automated metrics for video quality. Extensive experiments reveal that compositional editing remains a profound challenge: current models frequently omit edits, violate preservation constraints, or introduce artifacts when handling multiple operations simultaneously. CoVEBench provides a challenging, diagnostic testbed to advance video editing toward realistic user workflows.

21.
arXiv (CS.CL) 2026-06-18

Beyond Reward Engineering: A Data Recipe for Long-Context Reinforcement Learning

Long-context reasoning is an essential capability for large language models, particularly when they are deployed as autonomous agents that must reason over lengthy trajectories. Reinforcement learning (RL) has recently emerged as a dominant paradigm for improving this ability, yet existing work largely focuses on reward engineering while diverse training data remains scarce. We revisit this problem from a data-centric perspective and show that a simple yet effective data recipe alone, paired with a minimal outcome-based GRPO setup, suffices to substantially improve long-context reasoning. Our recipe targets three complementary task families – retrieval, multi-evidence synthesis, and reasoning – for which we construct and curate eight datasets totaling ~14K examples. Experiments on three models (Qwen3-4B/8B/30B-A3B) yield average gains of +7.2/+3.2/+6.4 points across seven long-context benchmarks, surpassing prior RL training sets. We further demonstrate that these gains transfer to agentic tasks, where continuing RL training on an agent-tuned model with our data recipe improves GAIA by +4.8 and BrowseComp by +7.0 points. We will release our datasets to facilitate future research.

22.
arXiv (CS.LG) 2026-06-16

Finite Resources False Discovery Rate Control in Structured Hypothesis Spaces

arXiv:2606.15393v1 Announce Type: cross Abstract: Scientific discovery relies on large-scale hypothesis testing. However, the capacity to identify true discoveries while controlling false discovery faces major challenges: obtaining relevant reference data (the null distribution) is resource-intensive, leaving finite-data uncertainty, and the procedure should account for the inherent structure in the hypothesis space, when such structure exists. Here, we present a framework for controlling the false discovery rate both when each hypothesis is evidenced only by a finite count of null draws, leaving its p-value uncertain, and when the hypothesis space carries arbitrary structure, requiring only that the structure be represented through a suitable reproducing kernel. We present two decision rules that are both robust to structural mis-specification, yet offer a distinct trade-off between exact FDR control and statistical power. The first rule guarantees exact FDR control; the second maximizes power by adapting mirror-statistic control into count space, utilizing an analytical framework to assess FDR control when exact mirror symmetry is relaxed. Furthermore, the tractability gained by the RKHS framework allows us to directly investigate finite-data uncertainties, which we leverage to suggest a policy for the efficient allocation of null distribution samples.

23.
bioRxiv (Bioinfo) 2026-06-16

Expanding gene regulatory networks from transcriptome data through graphical modeling with heterogeneous priors

Gene regulatory network inference is widely used to reconstruct large-scale networks and identify functional genes from transcriptome data. Meanwhile, in many biological fields, core regulatory genes have been extensively studied, leading to the establishment of small-scale gene regulatory networks, and novel genes connected to these networks remain to be identified. However, methods for expanding existing gene networks by identifying novel regulatory interactions, rather than reconstructing the entire network, are not well established. Here, we propose a method for gene network expansion that incorporates known regulatory relationships and evaluates each candidate gene individually to infer its regulatory connections to the existing network. Using simulated datasets from the DREAM4 benchmark and the PRECISE-1K experimental dataset, our method outperformed conventional methods by incorporating prior knowledge. In particular, it improved the ability to distinguish true regulatory interactions from indirect associations arising from strong correlations among genes in the existing network. The method also showed strong performance for interactions involving genes with high outdegree or centrality. Furthermore, it maintained stable performance as the size of the existing network increased and was robust to noise in prior information. These results demonstrate that our method provides an effective framework for expanding existing gene regulatory networks by leveraging prior knowledge.

24.
arXiv (CS.LG) 2026-06-12

Multi-Token Residual Prediction

arXiv:2605.18817v2 Announce Type: replace Abstract: Diffusion Language Models (DLMs) generate text by iteratively denoising masked token sequences, offering a tradeoff between parallelism and quality compared to autoregressive models. In current practice, the number of tokens decoded per step is controlled by a confidence threshold, and quality degrades monotonically as more tokens are denoised per step. We introduce Multi-token Residual Prediction (MRP), a lightweight module that enables dependency-aware multi-token denoising within a single backbone forward pass. MRP exploits a key property of the denoising process: the logit distributions at adjacent denoising steps are remarkably similar. Rather than running the backbone a second time to obtain the next-step logits, MRP predicts the residual between steps from the backbone's hidden states, effectively denoising more tokens per backbone forward at a fraction of the cost. We apply MRP across the two operating regimes of DLM decoding. In the high-quality-low-throughput static denoising regime, MRP serves as a drafter for speculative decoding: its proposals are verified against the backbone, yielding lossless acceleration of up to 1.4x in SGLang. In the low-quality-high-throughput dynamic denoising regime, MRP instead drives a remasking scheme that revokes over-eager reveals, recovering most of the accuracy lost to aggressive low-threshold decoding and improving accuracy by up to 22.6 points on code generation task HumanEval and 17.7 points on reasoning task GSM8K.

25.
arXiv (CS.AI) 2026-06-11

Categorical Prior Lock-in: Why In-Context Learning Fails for Structured Data

arXiv:2606.11961v1 Announce Type: cross Abstract: Large language models (LLMs) are increasingly used as conditional generators for structured data, relying on in-context learning (ICL) to adapt to new distributions without parameter updates. We investigate the limits of ICL for structured generation under distribution mismatch, using high-cardinality tabular data as a controlled test case, and identify a structural failure mode we term categorical prior lock-in: the inability of ICL to update the model's prior over token distributions inherited from pre-training. Across two 7B-parameter open-weight models, ICL improves numerical fidelity with additional examples but exhibits a sharp ceiling on categorical distributions, failing to reproduce rare classes entirely. Parameter-efficient fine-tuning (LoRA) overcomes these limitations but introduces measurable memorization risk and, in some cases, destabilizes structured output generation, highlighting a fundamental trade-off between adaptability and privacy.