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

Photon: Federated LLM Pre-Training

arXiv:2411.02908v2 Announce Type: replace Abstract: Scaling large language models (LLMs) demands extensive data and computing resources, which are traditionally constrained to data centers by the high-bandwidth requirements of distributed training. Low-bandwidth methods like federated learning (FL) could enable collaborative training of larger models across weakly-connected GPUs if they can effectively be used for pre-training. To achieve this, we introduce Photon, the first complete system for federated end-to-end LLM training, leveraging cross-silo FL for global-scale training with minimal communication overheads. Using Photon, we train the first federated family of decoder-only LLMs from scratch. We show that: (1) Photon can train model sizes up to 7B in a federated fashion while reaching an even better perplexity than centralized pre-training; (2) Photon model training time decreases with available compute, achieving a similar compute-time trade-off to centralized; and (3) Photon outperforms the wall-time of baseline distributed training methods by 35% via communicating 64x-512xless. Our proposal is robust to data heterogeneity and converges twice as fast as previous methods like DiLoCo. This surprising data efficiency stems from a unique approach combining small client batch sizes with extremely high learning rates, enabled by federated averaging's robustness to hyperparameters. Photon thus represents the first economical system for global internet-wide LLM pre-training.

02.
arXiv (CS.AI) 2026-06-12

A Mathematical Theory of Value: a synthesis on goal-directed agency under resource constraints

作者:

arXiv:2606.12502v1 Announce Type: cross Abstract: We propose that value – the quantity goal-directed agents create, destroy, and exchange – is a lawful structural quantity in the same category as information. Following Shannon's method, we make one ruthless abstraction: value is the rate at which an agent converts a resource into goal-progress, relative to a frame fixed by its goal. A scale-invariance axiom forces a logarithmic measure, $V=\sum_i k_i \ln e_i$; compounding of a reinvested resource forces the same form via the ergodicity argument of Peters (2019). The two routes are kin rather than independent; their agreement is a consistency check, not an over-determination. We derive a coding theorem of value: $\Delta G \le I(X;Y)$, achieved by Bayes-proportional allocation; realized value decomposes as $G=D(q\|r)-D(q\|p)$, identifying misalignment with measurable waste. For populations, value is frame-relative while price is frame-independent; a fleet that pools its resource and fuses its perception inherits the ceiling $G_{\mathrm{fleet}} \le I(X;Y_{1:m}) \le H(X)$ (a corollary; an earlier sum-form claim was wrong and is corrected in v5). A dynamical layer yields an is/ought asymmetry from which alignment emerges as a control-stability condition with a closed-form residual. We test the single-frame laws on live language models in a pre-registered scale-up: perception mutual information tracks realized capability rather than parameter count (Spearman $\rho = 0.977$ pooled over 30 model$\times$domain points), out-of-sample $\Delta G$ tracks $I(X;Y)$, and over-confidence is measurable dissipation; a further pre-registered test shows the bridge is shape-invariant across four task shapes ($n=42$, slope 0.953). None of the mechanisms is individually new – generalized Kelly, Armstrong & Mindermann (2018), classical control; the contribution is their unification and the governance mapping (incentive design over oversight) that follows.

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

MIDS: Detecting Stealthy Masquerade and Tampering Attacks on CAN Bus via Bidirectional Mamba

arXiv:2606.18599v1 Announce Type: cross Abstract: The Controller Area Network (CAN) protocol is the primary communication standard for Electronic Control Units (ECUs) in modern vehicles, but its lack of encryption and authentication exposes it to a range of security threats. Existing intrusion detection systems are largely tuned to fabrication-style attacks (DoS, fuzzing, ID spoofing realised by frame injection), in which detection signals such as per-ID inter-arrival statistics are readily available. We instead address the harder masquerade setting[b37], in which an internal adversary substitutes a legitimate frame in-situ at its original transmission slot, preserving traffic periodicity and rendering traffic-statistic defences ineffective. We propose the Mamba Intrusion Detection System (MIDS), an innovative dual-stream framework that processes CAN identifiers and payloads in parallel and reconstructs their joint temporal semantics through bidirectional selective state-space modelling. To evaluate MIDS, we collected over 100 million CAN frames from a physical Tesla Model 3 across three driving regimes and synthesised 54 masquerade attack variants spanning ID-only, data-only, and combined modifications. MIDS attains an F1 of 96.94\% on this dataset, exceeding the strongest reproducible baseline by more than 8 percentage points, while sustaining a 1.147~ms single-window inference latency – ample headroom for real-time onboard deployment. To verify generalisation, we further evaluate MIDS on four public benchmarks (ROAD, CrySyS, OTIDS, CT\&T) covering both masquerade and injection scenarios; MIDS attains F1 from 93.70\% to 99.61\%, outperforming the strongest of eight reproduced baselines by up to 13.94 percentage points under a unified 5-fold protocol.

04.
arXiv (CS.LG) 2026-06-17

AIMER: Calibration-Free Task-Agnostic MoE Expert Pruning

arXiv:2603.18492v3 Announce Type: replace Abstract: Mixture-of-Experts (MoE) language models increase parameter capacity without proportional per-token computation, yet deployment still requires storing the full expert pool, making expert pruning important for reducing memory and serving overhead. Existing task-agnostic expert-pruning methods are typically calibration-dependent: they estimate expert importance from routing or activation statistics on a calibration set, making pruning decisions sensitive to calibration-data variation while introducing substantial preprocessing cost. We propose AIMER (Absolute mean over root mean square IMportance for Expert Ranking), a simple calibration-free criterion that identifies more distinct experts by capturing the concentration pattern of expert weights, making it well suited for task-agnostic expert pruning. Across 7B to 47B MoE language models with distinct architectures and 16 diverse benchmarks, AIMER consistently delivers stronger capability balance across diverse tasks than existing calibration-free methods. Surprisingly, AIMER also achieves better balance than strong calibration-based expert-pruning baselines calibrated on the widely used task-agnostic C4 corpus, while requiring only 0.22–2.06 seconds to score all experts.

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

InterleaveThinker: Reinforcing Agentic Interleaved Generation

Recent image generators have demonstrated impressive photorealism and instruction-following capabilities in single-image generation and editing. However, constrained by their architectures, they cannot achieve interleaved generation (text-image sequence), which has crucial applications in visual narratives, guidance, and embodied manipulation. Even the latest open-source Unified Multimodal Models (UMMs) exhibit limited performance in this regard. In this paper, we introduce InterleaveThinker, the first multi-agent pipeline designed to endow any existing image generator with interleaved generation capabilities. Specifically, we employ a planner agent to organize the image-text input sequence, instructing the image generator on the required execution at each step. Subsequently, we introduce a critic agent to evaluate the generator's outputs, identify samples that deviate from the planned instructions, and refine the instructions for regeneration. To implement this pipeline, we construct the Interleave-Planner-SFT-80k and Interleave-Critic-SFT-112k to perform a format cold-start. Then we develop Interleave-Critic-RL-13k to reinforce the step-wise instruction correction capability within a generation trajectory using GRPO. Since a single interleaved generation trajectory may involve over 25 generator calls, optimizing the entire trajectory is computationally impractical. Therefore, we propose accuracy reward and step-wise reward, allowing single-step RL to effectively guide the entire generation trajectory. The results show that InterleaveThinker improves performance across various image generators. On interleaved generation benchmarks, it achieves performance comparable to Nano Banana and GPT-5. Surprisingly, it also significantly enhances the base model on reasoning-based benchmarks; for example, on 4-step FLUX.2-klein, we observe substantial gains on WISE and RISE.

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

Compatibility-Aware Dynamic Fine-Tuning for Large Language Models

Supervised Fine-Tuning (SFT) is the predominant paradigm for aligning large language models (LLMs), yet it suffers from optimization instability and limited generalization. Recent work attributes this issue to pathological gradient scaling and proposes Dynamic Fine-Tuning (DFT) to correct it at the token level. However, DFT assumes all demonstrations are equally suitable learning targets, an assumption violated by the strong heterogeneity of large-scale instruction data, where demonstration-policy mismatch induces high-variance updates at the sample level. We introduce Compatibility-Aware Dynamic Fine-Tuning (CADFT), a principled extension of DFT that controls sample-level optimization variance. CADFT derives a dynamic, policy-dependent compatibility signal from model likelihoods to modulate supervised updates, suppressing high-variance gradients from incompatible demonstrations. We further propose a delayed, low-frequency compatibility-guided rewriting strategy to transform persistently incompatible demonstrations into learnable targets. We show that CADFT can be interpreted as a variance-controlled estimator that generalizes token-level stabilization in DFT to the sample level. Extensive experiments demonstrate improved stability, generalization, and cold-start reinforcement learning initialization, while remaining fully supervised and independent of explicit reward modeling.

07.
medRxiv (Medicine) 2026-06-12

Genetic basis of dynamic brain states reveals cellular and disease associations

Dynamic resting-state fMRI captures the time-varying patterns of brain activity that are obscured by static approaches. Hidden Markov Models (HMMs) characterise these dynamics as recurring whole-brain states and quantify their fractional occupancy (FO), the proportion of time spent in each state, yet the biological basis of inter-individual variation in FO remains unclear. Using data from 52,335 White UK Biobank participants, with replication in East and South Asian subsamples, this study examined the heritability, cellular and neurotransmitter basis of brain states, and their links with complex phenotypes. FO was significantly heritable and enriched for neuronal populations, particularly glutamatergic and GABAergic signalling. Analyses identified shared and state-specific loci and revealed genetic correlations, colocalisation, and potential causal relationships between FO and several phenotypes, including educational attainment, sleep duration, and disease risk. These findings establish dynamic brain states as biologically grounded intermediate phenotypes, linking genetic variation to neural dynamics, diseases and traits.

08.
arXiv (CS.AI) 2026-06-18

SAGE: Retain-Aware Post-Hoc Sanitization of Final Unlearning Vector

arXiv:2606.18309v1 Announce Type: cross Abstract: Large Language Model (LLM) unlearning aims to remove undesirable knowledge or behaviors while preserving retained capabilities. Current unlearning methods all involve a trade-off between unlearning and retention. We have found that the retention activation bias can also be used to quantify the damage an unlearning method inflicts on retention, without considering the specific implementation of the unlearning process. This allows us to restore retention performance for any unlearning method using a post-hoc approach. Therefore, we propose a complementary post-hoc setting to sanitize the final update vector without rerunning the original unlearning pipeline. In this setting, we design SAGE, Spectral Activation-GEometry Sanitization, a source-agnostic correction for final unlearning updates. SAGE collects real module inputs from a small retain proxy, extracts their dominant activation geometry, and solves a source-anchored optimization objective in closed form, which suppresses update components aligned with high-energy retained directions while preserving the source method's forgetting carrier. Across multiple unlearning methods, model scales, and benchmarks, SAGE consistently relieves the retain-forget trade-off, identifying post-hoc sanitization of final vectors as a practical and underexplored axis for machine unlearning.

09.
arXiv (CS.LG) 2026-06-11

Triangular-Reference Schrödinger Bridges for Time Series Generation

arXiv:2605.27478v3 Announce Type: replace-cross Abstract: Schrödinger bridges for time series (SBTS) generate synthetic paths by projecting, in relative entropy, a Brownian reference onto the path laws that match the joint distribution of the data on the observation grid. The Brownian reference, however, fixes the quadratic variation of the generated paths, which is restrictive when stochastic volatility, correlated noise, or rank-deficient covariance structures must be reproduced. We introduce "Triangular-Reference Schrödinger Bridges for Time Series" (TR-SBTS), which keeps the entropy-projection backbone of SBTS but replaces the Brownian reference by a triangular, volatility-informed, intervalwise frozen reference on a state augmented with latent covariance descriptors. The construction remains a single entropy projection on the augmented state: the minimiser is the \(h\)-transform of the reference, and on each frozen interval the optimal drift has the logarithmic-gradient form \(b^\star(t,x)=A\,\nabla\log H(t,x)\), intrinsic to the active covariance directions when the frozen covariance \(A\) is degenerate. We prove stability of the frozen approximation and consistency of the associated regularised kernel estimators, describe a reference-aware Nadaraya–Watson implementation of the conditional next-increment law, and evaluate the construction on numerical experiments.

10.
arXiv (CS.AI) 2026-06-11

Estimating Tail Risks in Language Model Output Distributions

arXiv:2604.22167v2 Announce Type: replace-cross Abstract: Language models are increasingly capable and are being rapidly deployed on a population-level scale. As a result, the safety of these models is increasingly high-stakes. Fortunately, advances in alignment have significantly reduced the likelihood of harmful model outputs. However, when models are queried billions of times in a day, even rare worst-case behaviors will occur. Current safety evaluations focus on capturing the distribution of inputs that yield harmful outputs. These evaluations disregard the probabilistic nature of models and their tail output behavior. To measure this tail risk, we propose a method to efficiently estimate the probability of harmful outputs for any input query. Instead of naive brute-force sampling from the target model, where harmful outputs could be rare, we operationalize importance sampling by creating unsafe versions of the target model. These unsafe versions enable sample-efficient estimation by making harmful outputs more probable. On benchmarks measuring misuse and misalignment, these estimates match brute-force Monte Carlo estimates using 10-20x fewer samples. For example, we can estimate probability of harmful outputs on the order of 10^-4 with just 500 samples. Additionally, we find that these harmfulness estimates can reveal the sensitivity of models to perturbations in model input and predict deployment risks. Our work demonstrates that accurate rare-event estimation is both critical and feasible for safety evaluations. Code is available at https://github.com/rangell/LMTailRisk

11.
arXiv (CS.LG) 2026-06-16

Rethinking Structural Anomaly Detection: From Decision Boundaries to Projection Operators

arXiv:2606.15280v1 Announce Type: new Abstract: Most existing anomaly detection methods rely on estimating a probability density or learning an enclosing decision boundary, implicitly assuming that normal data occupies a region of non-zero volume in the ambient space. In contrast, structural anomaly detection considers data that lies near a low-dimensional manifold, creating a mismatch between the inductive bias of existing methods and the structure of the data, often resulting in degraded performance. To address this mismatch, we introduce a geometric perspective. Specifically, we learn a projection operator onto the manifold of normal samples and define a sample as anomalous if it is altered by this projection. This formulation naturally integrates the inductive bias of manifold-supported data and reframes anomaly detection in terms of a projection residual, thereby resolving issues arising from modeling degenerate distributions. Notably, it provides a unifying interpretation of reconstruction-based methods by explaining their success and failure in terms of projection quality. In particular, it explains the strong generalization ability of projection-aligned models as a consequence of contraction behavior toward the manifold. Moreover, by decoupling anomaly detection from probabilistic modeling, it reduces the tendency to misclassify rare but normal samples, a widely recognized limitation of existing approaches. Empirically, we demonstrate that projection-aligned methods achieve strong performance, outperforming boundary-based methods while improving upon existing reconstruction-based approaches.

12.
arXiv (CS.CV) 2026-06-17

DRIVESPATIAL: A Benchmark for Spatiotemporal Intelligence in VLMs for Autonomous Driving

Spatiotemporal intelligence in autonomous driving (AD) requires an agent to integrate multi-view observations into a coherent scene representation, maintain object continuity across viewpoints and time, and reason about spatial relations, interactions, and future dynamics. However, existing AD vision-language benchmarks largely focus on single-view, static, ego-centric, or single-source question answering, leaving it unclear whether current Vision-Language Models (VLMs) can truly construct and reason over dynamic driving scenes. We introduce DriveSpatial, a benchmark of 15.6K human-verified QA pairs across 20 tasks from five large-scale AD datasets. DriveSpatial evaluates four abilities: Cognitive Scene Construction, Multi-view Relational Understanding, Temporal Reasoning, and Generalization. Unlike prior benchmarks, DriveSpatial is generated from a dynamic multi-relational scene graph that encodes object states, spatial relations, interactions, camera visibility, and temporal correspondences, enabling QA pairs that enforce genuine cross-view and spatiotemporal reasoning. Evaluating 15 representative VLMs reveals a substantial human-model gap: the strongest model trails humans by 28.4 points, with Cognitive Scene Construction emerging as the key bottleneck. Further diagnostics show that language-only prompting is insufficient, while explicit BEV grounding consistently improves performance. These results suggest that current VLMs lack the scene-construction ability needed for reliable spatiotemporal driving intelligence. DriveSpatial and its construction pipeline will be released to support future research.

13.
arXiv (CS.LG) 2026-06-15

Concatenated Matrix SVD: Compression Bounds, Incremental Approximation, and Error-Constrained Clustering

arXiv:2601.11626v2 Announce Type: replace-cross Abstract: Large collections of matrices arise throughout modern machine learning, signal processing, and scientific computing, where they are commonly compressed by concatenation followed by truncated singular value decomposition (SVD). This strategy enables parameter sharing and efficient reconstruction and has been widely adopted across domains ranging from multi-view learning and signal processing to neural network compression. However, it leaves a fundamental question unanswered: which matrices can be safely concatenated and compressed together under explicit reconstruction error constraints? Existing approaches rely on heuristic or architecture-specific grouping and provide no principled guarantees on the resulting SVD approximation error. In the present work, we introduce a theory-driven framework for compression-aware clustering of matrices under SVD compression constraints. Our analysis establishes new spectral bounds for horizontally concatenated matrices, deriving global upper bounds on the optimal rank-$r$ SVD reconstruction error from lower bounds on singular value growth. The first bound follows from Weyl-type monotonicity under blockwise extensions, while the second leverages singular values of incremental residuals to yield tighter, per-block guarantees. We further develop an efficient approximate estimator based on incremental truncated SVD that tracks dominant singular values without forming the full concatenated matrix. Therefore, we propose three clustering algorithms that merge matrices only when their predicted joint SVD compression error remains below a user-specified threshold. The algorithms span a trade-off between speed, provable accuracy, and scalability, enabling compression-aware clustering with explicit error control.

14.
arXiv (CS.LG) 2026-06-18

Stochastic Thermodynamics and SDE-based Generative Models

作者:

arXiv:2606.18290v1 Announce Type: cross Abstract: SDE-based generative models, including diffusion models and the Schrödinger bridge, have found broad applications in signal processing tasks such as speech enhancement, image restoration, and time-series generation. This note presents a modeling framework for such models within the context of stochastic thermodynamics. The main results of this note are trajectory-level definitions of work, heat, and entropy production, along with a generalized Jarzynski identity and a second-law-like inequality. The proposed framework extends the original Jarzynski setup to accommodate time-dependent bath temperature and nonconservative driving forces. This thermodynamic perspective may deepen our understanding of diffusion models and the Schrödinger bridge from a nonequilibrium statistical mechanics viewpoint.

15.
arXiv (CS.CL) 2026-06-12

When Does Mixing Help? Analyzing Query Embedding Interpolation in Multilingual Dense Retrieval

While mixed-language querying is ubiquitous in multilingual communities, the sensitivity of dense retrievers to such queries remains poorly understood. We present a ratio-controlled study on mMARCO that systematically evaluates retrieval performance by varying the mixing proportion of parallel query translations via embedding-level mixing – constructing mixed queries as an interpolation of monolingual embeddings. Experiments with BGE-M3 demonstrate that an optimal mixing ratio outperforms the best monolingual endpoint in 88/105 cases. We uncover a distinct asymmetry driven by English dominance: mixing is uniformly beneficial when retrieving from non-English document indices, whereas indices containing English are best served by pure English queries. Furthermore, English acts as the strongest mixing partner for every non-English document language. Finally, when controlling for English dominance, mixing gains correlate negatively with typological distance. We conclude that language-mix sensitivity is structured and predictable, and we validate the robustness of these patterns across model families and scales.

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

Adaptive and Explicit safe: Triggering Latent Safety Awareness in Large Reasoning Models

arXiv:2606.16808v1 Announce Type: new Abstract: While Large Reasoning Models (LRMs) excel at complex tasks, they remain highly vulnerable to sophisticated jailbreaks and direct harmful queries. To address this vulnerability, prior works depend heavily on external manual data annotation for safety alignment. However, we observe that LRMs can inherently identify safety risks when being re-presented with original queries alongside their own reasoning trajectories – a capability we term Latent Safety Awareness. To leverage this safety awareness, we first employ Supervised Fine-Tuning (SFT) to explicitly induce safe tags to trigger safety analysis and guidance following the initial reasoning content for unsafe queries, while preserving standard responses for general queries to ensure adaptive triggering. Subsequently, we apply Direct Preference Optimization (DPO) to further enhance the correctness and stability of the safety analysis and guidance. Notably, responses required for both training stages are entirely generated by models being optimized. With (Safe Trigger) SFT and DPO, experimental results demonstrate significant safety enhancement. For example, the Attack Success Rate (ASR) of DeepSeek-R1-Distill-Llama-8B, on average, drops 24.65% and 36.72% on harmful and jailbreak benchmarks, respectively. Finally, our Safe Trigger method exerts almost no negative impact on general performance or user experience.

17.
medRxiv (Medicine) 2026-06-17

Characterisation of disease progression in hantavirus haemorrhagic fever with renal syndrome

Hantaviruses can cause haemorrhagic fever with renal syndrome (HFRS). This is a clinically variable disease in which severe outcomes are hypothesized to arise from dysregulated host responses. To characterise this, longitudinal, label-free plasma proteomics was used to compare disease progression in a unique well-defined cohort of patients infected with either Dobrava virus (DOBV) or Puumala virus (PUUV) hantaviruses. Patients were stratified by clinical severity. The average viral load in the first available sample from hospitalized patients was higher in those who went on to have severe infection, and higher in patients infected with DOBV. There was marked separation of infected patients from controls across early, mid and late disease, including after viral RNA clearance, suggesting a sustained systemic host-response signature. Proteomic signatures were consistent with a strong acute-phase response in both mild and severe disease. There was evidence of activation of the adaptive humoral response at later stages. Hierarchical clustering identified severity-associated pathways linked to endothelial dysfunction, thrombocytopenia, vascular leakage and renal injury. These findings define a durable plasma proteomic signature of hantavirus disease and support a model in which severe HFRS is driven by persistent inflammatory, complement and platelet/coagulation pathway activation rather than viral burden alone.

18.
arXiv (CS.AI) 2026-06-11

DataEvolver: Automatic Data Preparation for Large Language Models through Multi-Level Self-Evolving

arXiv:2606.07001v2 Announce Type: replace-cross Abstract: High-quality training data is essential to large language models (LLMs) and typically requires extensive and costly manual curation. Existing automatic data preparation methods rely on predefined pipelines or customized human instructions, which limits their adaptability to diverse data distributions and lacks principled guidance from high-quality examples. In this paper, we introduce DataEvolver, the first self-evolving data preparation system that automatically constructs pipelines to transform raw data into high-quality data. DataEvolver employs a multi-level mechanism to ensure both pipeline executability and effectiveness. At the operator level, it incrementally expands the operator set to construct a logical plan while resolving dependency conflicts. At the pipeline level, it instantiates logical plans into executable code and iteratively refines pipeline orchestration through a feedback loop that reduces the distribution gap between prepared data and high-quality examples. Experiments on seven benchmarks show that DataEvolver substantially improves data quality and achieves an average 10\% gain in downstream LLM performance compared with training on original data, highlighting new opportunities for the iterative co-evolution of LLMs and data.

19.
Nature Medicine 2026-06-09

Adjuvanted inactivated rabies virus-vectored Lassa virus vaccine in healthy adults: a phase 1 trial

Lassa fever causes substantial morbidity and mortality in West Africa, and no licensed vaccine is available. We evaluated LASSARAB, an inactivated rabies virus-vectored Lassa virus (Josiah strain) glycoprotein complex vaccine. We conducted a randomized, controlled, dose-escalation phase 1 trial. Participants (total n = 54) received two intramuscular doses of LASSARAB containing 700 (n = 15), 1,400 (n = 15) or 2,800 (n = 14) relative units of antigen formulated with the TLR-4 agonist 3D-6-acyl PHAD-SE adjuvant, or licensed rabies vaccine control (n = 10), administered 28 days apart. This protocol-defined interim analysis reports the primary safety evaluation and secondary immunogenicity assessments through day 61. There were no prespecified hypotheses or formal power calculations. All primary safety end points demonstrated an acceptable safety profile. After dose 1, local solicited adverse events occurred in 86.7–100.0% of LASSARAB groups and 80% of controls; systemic events in 33.3–71.4% and 60.0% of controls. After dose 2, local solicited adverse events occurred in 66.7–86.7% of LASSARAB groups and 55.6% of controls; systemic events in 53.3–71.4% of LASSARAB groups and 55.6% of controls. Events were predominantly mild and self-limited. Unsolicited adverse events occurred in 28.6–60.0% of LASSARAB groups and 20.0% of controls. No serious adverse event, immune-mediated condition or sensorineural hearing loss occurred. Safety laboratory abnormalities occurred in 13.3–66.7% of LASSARAB groups and 30.0% of controls (14 mild, 6 moderate and none severe). After two doses, Lassa virus GPC IgG ELISA seroconversion (≥fourfold rise) was achieved in 100.0% (44 of 44) of LASSARAB recipients and 0.0% (0 of 10) of controls. Rabies glycoprotein IgG ELISA seroconversion (≥fourfold rise) and neutralizing antibody by rapid fluorescent focus inhibition test (RFFIT) seroprotection (≥0.5 IU ml−1) were also 100% across all groups, including controls. LASSARAB + 3D-6-acyl phosphorylated hexaacyl disaccharide (PHAD)-SE demonstrated a favorable safety profile and immunogenicity against Lassa and rabies viruses. The per-protocol final study report will include safety and durability through day 394. ClinicalTrials.gov identifier NCT06546709 . An interim report of a first-in-human phase 1 trial found an adjuvanted, combination inactivated rabies-vectored, Lassa fever vaccine (LASSARAB + 3D-6-acyl PHAD-SE) to be safe and induced immunogenicity to both Lassa and rabies viruses in healthy participants.

20.
Nature (Science) 2026-06-10

Molecular glue degraders of HuR suppress BRAF-mutant colorectal cancer

作者:

BRAF gain-of-function mutations, particularly BRAF(V600E), affect roughly 10% of all patients with colorectal cancer (CRC), and portend poor prognosis with limited therapeutic interventions. BRAF inhibitors such as encorafenib are ineffective due to MAPK pathway reactivation driven by BRAF dimerization. Combined inhibition of BRAF and EGFR, although approved therapies, results in short survival benefits and frequent treatment resistance and relapse1–3. Here, through rational chemical library design coupled with parallel proteomic screening, we identified dHuR as a molecular glue degrader of human antigen R (HuR), an RNA-binding protein that drives tumour growth, invasion and therapy resistance. dHuR binds to the CRBN ubiquitin ligase to create a unique benzofuran-tethered composite surface to recruit HuR as a neosubstrate by engaging its β-hairpin G-loop degron, as revealed by the cryo-electron microscopy structure of the ternary complex. dHuR abrogated BRAF expression by inducing its exon 18 skipping, and demonstrated superior suppression of BRAF-mutant CRC tumours including those gaining resistance to BRAF inhibitors. Finally, we performed kinome library CRISPR screening and revealed that inactivation of EGFR or MEK enhanced dHuR cytotoxicity, thus establishing a combinatorial strategy to treat patients with refractory BRAF-mutant CRC. Molecular glue degraders of the RNA-binding protein HuR have therapeutic potential for BRAF-mutant cancers.

21.
medRxiv (Medicine) 2026-06-17

Efficacy of a Gamified Digital Platform for Substance Use Education and Overdose Prevention Among College Students: a Pilot and Feasibility Study

Background: For US young adults aged 18-25 in the 2018-2024 period, fentanyl was involved in 78.2% of the 44,020 unintentional or undetermined-intent overdose deaths, most often co-involving stimulants and other non-opioid substances. While fatal overdose rates in this age group have fallen to their lowest recorded level, emergency medical services-attended non-fatal overdose events have reached record highs, shifting the decisive variable toward bystander recognition and response. College students report near-universal alcohol education but minimal education on the substances actually driving overdose mortality. Methods: We conducted a single-group pre-post evaluation of the DopaGE Portal, a gamified, mastery-based digital platform covering cocaine, MDMA, benzodiazepines, and opioid overdose response, deployed at a public university (UNL) and a multi-campus volunteer network (TACO). Paired pre/post surveys (N=42) measured self-efficacy (7 items; primary), behavioral intentions, risk perception, and knowledge/attitudes on 5-point scales, plus four factual knowledge questions. Paired t-tests, exact McNemar tests, and Benjamini-Hochberg correction across eight primary tests were applied. Institutional naloxone distribution at UNL was tracked as an ecological behavioral outcome. A mandated high-school cohort (N=94) provided supplementary acceptability data. Results: Self-efficacy increased from 2.82 to 4.46 (d=2.00, 95% CI 1.46-2.55; adjusted p

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

Sinkhorn-CPD: Robust point cloud registration via unbalanced entropic optimal transport

Coherent Point Drift (CPD) is widely used for rigid point cloud registration because of its soft correspondences and closed-form parameter updates. However, CPD's target-side marginal constraint forces every observation, including outliers, to receive exactly unit probability mass. This assumption degrades registration accuracy under heavy outliers and partial overlap. Optimal transport (OT) methods can handle missing mass through unbalanced formulations, but require hand-tuned annealing schedules. In this paper, we propose Sinkhorn-CPD, which replaces CPD's target-side marginal constraint with dual Kullback-Leibler penalties, allowing the algorithm to discard outliers on both sides. The resulting formulation is a fully unbalanced entropic optimal transport problem, which can be efficiently solved by generalized Sinkhorn iterations. Moreover, Sinkhorn-CPD preserves the closed-form Procrustes and variance updates of CPD. In our method, the variance sigma^2 plays the role of the entropic regularization parameter, which induces an automatic annealing schedule from diffuse to sharp correspondences without manual temperature tuning. Experiments on synthetic, cross-category, and scan-to-CAD benchmarks show that Sinkhorn-CPD achieves state-of-the-art accuracy, with strong robustness to outliers and partial overlap.

23.
PLOS Computational Biology 2026-06-15

Environmental “knees” and “wiggles” as strong stabilizers of species’ range limits set by interspecific competition

by Farshad Shirani, Benjamin G. Freeman Whether interspecific competition is a major contributing factor to setting species’ range limits has been debated for a long time. Theoretical studies have proposed that the interactions between interspecific competition and disruptive gene flow along an environmental gradient can halt range expansion of ecologically similar species where they meet. However, the stability of such range limits has not been well addressed. We use a deterministic mathematical model of adaptive range evolution over a continuous habitat to show that the range limits set by interspecific competition are unlikely to be evolutionarily stable if the environmental optima for fitness-related traits vary (almost) linearly in space. That is, in a linear environment without a dispersal barrier or a third (or more) species, the range borders formed between two competing species constantly move towards the weaker species. We demonstrate that environmental nonlinearities such as “knees” and “wiggles”—wherein an isolated sharp change or a step-like change occurs in the steepness of a trait optimum—can strongly stabilize competitively formed range limits. The stabilization mechanism relies on the contrast that such nonlinearities create in the level of disruptive gene flow to the peripheral population of each species, and succeeds when an additional process, such as Allee effects, prevents the establishment of an infinitesimal population in the presence of an abundant competitor. We show that the stability of the range limits at these nonlinearities is robust against moderate environmental disturbances. Whether strong disturbances such as rapid high-amplitude climate changes can destabilize such range limits depends on how the competitive dominance of the species changes across the nonlinearity. Therefore, our findings underscore the importance of assessing species’ competitive ability when predicting responses to climate change, and identify geographic regions where established range limits are likely to persist as well as regions where shifting limits may eventually stabilize.

24.
arXiv (CS.LG) 2026-06-16

Task-Error Residual Learning for Real-Robot Five-Ball Juggling

arXiv:2606.16978v1 Announce Type: cross Abstract: For residual learning that refines existing behavior, sample efficiency depends on two things: how much information each rollout returns, and how efficiently the learner uses that information. Reinforcement learning's standard scalar reward carries far less information than the directional task error that defines the task. Random exploration further discards whatever information each rollout returns. Through residual learning with directional task-error supervision and a task error model that drives sample selection, we achieve stable three-, four-, and five-ball juggling on anthropomorphic Barrett WAM arms. Despite planning and controlling through a simple, idealized stack, the system converges from the second attempt. The first attempt drops, after which task error decreases monotonically without further failures. In comparison, five-ball juggling typically takes humans years of practice. We compare residual learners across two ternary axes, the directional information in the learning feedback and the commitment of the analytic prior, spanning Newton-style Jacobian updates, Composite Bayesian Optimization, and stochastic search methods. Both axes prove necessary: neither directional feedback nor an informative prior suffices alone, and the simplest method that combines them, a fixed-Jacobian Newton update, is the most reliable. The learned residual tolerates substantial prior misalignment and degraded joint tracking, affecting mainly convergence speed. The bottleneck for residual learning on real robots is therefore the information content of the supervision signal and how the learner uses it, not the accuracy of the surrounding stack. Video documentation of all experiments is available at https://kai-ploeger.com/residual-juggling.

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arXiv (CS.CV) 2026-06-18

OneCanvas: 3D Scene Understanding via Panoramic Reprojection

Existing approaches to 3D scene understanding in Vision-Language Models (VLMs) either rely on complex, model-specific geometry encoders or large training budgets in pursuit of spatial reasoning. Instead, OneCanvas aggregates patch features from all views onto a single equirectangular panoramic canvas. Namely, each patch is unprojected to a 3D world coordinate using its depth and camera pose, then placed on the canvas at the continuous longitude and latitude of that point as seen from the canvas origin, with no rasterization or aggregation across overlapping views. A 3D position embedding of the patch's metric coordinates is added to its feature, restoring the depth lost when collapsing the world position to an angular canvas coordinate. Patches from all frames thus share one spatial coordinate system with no fusion or major architectural modifications of the backbone. The pretrained VLM consumes this representation as if it were an ordinary image. Because the canvas can be centered on any pose of interest, the same representation directly supports situated reasoning from a specific viewpoint, a common requirement in robotics and embodied AI. Thanks to this representation, we can also introduce a spatial pretraining curriculum: by procedurally placing patch features of objects, drawn from real images, at chosen 3D world positions on an otherwise empty canvas, we generate on-the-fly supervision spanning a broad range of spatial reasoning tasks, with answer distributions controlled to reduce spatial reasoning shortcuts. OneCanvas achieves state-of-the-art accuracy on SQA3D and VSI-Bench, and generalizes to out-of-distribution data on SPBench, using an order of magnitude less training compute than the strongest competing methods.