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Efficient amyloid-Ξ² degradation in Alzheimer’s disease using SPYTACs

SPYTAC is a synthetic peptide-programmed targeted protein degradation platform harnessing LRP1 to drive lysosomal degradation of extracellular amyloid-Ξ² in the brain and periphery. In 5Γ—FAD mice, SPYTAC treatment efficiently degrades amyloid-Ξ², preserves neurons, and improves cognition with reduced neuroinflammation and microhemorrhage when compared with antibody therapy.
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PERMA: Benchmarking Personalized Memory Agents via Event-Driven Preference and Realistic Task Environments

arXiv:2603.23231v1 Announce Type: new Abstract: Empowering large language models with long-term memory is crucial for building agents that adapt to users' evolving needs. However, prior evaluations typically interleave preference-related dialogues with irrelevant conversations, reducing the task to needle-in-a-haystack retrieval while ignoring relationships between events that drive the evolution of user preferences. Such settings overlook a fundamental characteristic of real-world personalization: preferences emerge gradually and accumulate across interactions within noisy contexts. To bridge this gap, we introduce PERMA, a benchmark designed to evaluate persona consistency over time beyond static preference recall. Additionally, we incorporate (1) text variability and (2) linguistic alignment to simulate erratic user inputs and individual idiolects in real-world data. PERMA consists of temporally ordered interaction events spanning multiple sessions and domains, with preference-related queries inserted over time. We design both multiple-choice and interactive tasks to probe the model's understanding of persona along the interaction timeline. Experiments demonstrate that by linking related interactions, advanced memory systems can extract more precise preferences and reduce token consumption, outperforming traditional semantic retrieval of raw dialogues. Nevertheless, they still struggle to maintain a coherent persona across temporal depth and cross-domain interference, highlighting the need for more robust personalized memory management in agents. Our code and data are open-sourced at https://github.com/PolarisLiu1/PERMA.
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Author Correction: Gut stem cell necroptosis by genome instability triggers bowel inflammation

Nature, Published online: 11 March 2026; doi:10.1038/s41586-026-10302-3

Author Correction: Gut stem cell necroptosis by genome instability triggers bowel inflammation
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Mapping Overlaps in Benchmarks through Perplexity in the Wild

arXiv:2509.23488v4 Announce Type: replace Abstract: We introduce benchmark signatures to characterize the capacity demands of LLM benchmarks and their overlaps. Signatures are sets of salient tokens from in-the-wild corpora whose model token perplexity, reflecting training exposure, predicts benchmark performance. We extract them via stepwise forward selection with linear regression in a meta-evaluation spanning 32 LLMs and 89 benchmarks across diverse domains. We then analyze how these signatures relate to both the semantic similarity of benchmark questions and the correlation structure of model performance. While performance correlations are uniformly high and semantic overlaps stay in a narrow mid-range, benchmark signatures reveal more nuanced structure. For instance, they uncover substantial overlap between benchmarks in knowledge and reasoning tasks, whereas benchmarks in culture- and humanity-oriented domains show low similarity with each other. Unlike raw performance correlations, which are influenced by benchmark-orthogonal factors such as question formats, signatures are robust to such confounds. We further identify cross-functional overlaps between logic, math, language, instruction following, and cultural/world modeling, with coding emerging as the most isolated function, interacting only moderately with the ability of detecting missing information. Qualitative analysis shows that only the knowledge signature aligns with actual knowledge, suggesting that LLM semantic organization may differ from human conceptual structure. Together, these findings offer insights into benchmark validity, LLM sensitivities, and the landscape of interconnected LLM capacities. We have open-sourced the code and data in this https://github.com/siyangwu1/Benchmark-Signature-Repository.
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FreeKV: Boosting KV Cache Retrieval for Efficient LLM Inference

arXiv:2505.13109v5 Announce Type: replace-cross Abstract: Large language models (LLMs) are widely deployed with rapidly expanding context windows to support increasingly demanding applications. However, long contexts pose significant deployment challenges, primarily due to the KV cache whose size grows proportionally with context length. While KV cache compression methods have been proposed to address this issue, KV dropping methods incur considerable accuracy loss, and KV retrieval methods suffer from significant efficiency bottlenecks. We propose FreeKV, a training-free algorithm-system co-optimization framework to enhance KV retrieval efficiency while preserving accuracy. On the algorithm side, FreeKV introduces speculative retrieval to shift the KV selection and recall processes out of the critical path, combined with fine-grained correction to ensure accuracy. On the system side, FreeKV employs hybrid KV layouts across CPU and GPU memory to eliminate fragmented data transfers, and leverages double-buffered streamed recall to further improve efficiency, enabling effective overlap with computation, full latency hiding, and practical speedups from speculative recall. Experiments demonstrate that FreeKV achieves near-lossless accuracy across various scenarios and models, delivering up to a 13$\times$ speedup compared to SOTA KV retrieval methods. Code is available at https://github.com/sjtu-zhao-lab/FreeKV.
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Chimera: Neuro-Symbolic Attention Primitives for Trustworthy Dataplane Intelligence

arXiv:2602.12851v2 Announce Type: replace-cross Abstract: Deploying expressive learning models directly on programmable dataplanes promises line-rate, low-latency traffic analysis but remains hindered by strict hardware constraints and the need for predictable, auditable behavior. Chimera introduces a principled framework that maps attention-oriented neural computations and symbolic constraints onto dataplane primitives, enabling trustworthy inference within the match-action pipeline. Chimera combines a kernelized, linearized attention approximation with a two-layer key-selection hierarchy and a cascade fusion mechanism that enforces hard symbolic guarantees while preserving neural expressivity. The design includes a hardware-aware mapping protocol and a two-timescale update scheme that together permit stable, line-rate operation under realistic dataplane budgets. The paper presents the Chimera architecture, a hardware mapping strategy, and empirical evidence showing that neuro-symbolic attention primitives can achieve high-fidelity inference within the resource envelope of commodity programmable switches.
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LLM Probability Concentration: How Alignment Shrinks the Generative Horizon

arXiv:2506.17871v3 Announce Type: replace-cross Abstract: Despite their impressive capabilities, aligned large language models (LLMs) often generate outputs that lack diversity. What drives this consistency in the generation? We investigate this phenomenon through the lens of probability concentration in the model's output distribution. To quantify this concentration, we introduce the *Branching Factor* (BF) -- a token-invariant measure of the effective number of plausible next steps during generation. Our empirical analysis reveals two key findings: (1) BF often decreases as generation progresses, suggesting that LLMs become more predictable as they generate. (2) alignment tuning substantially sharpens the model's output distribution from the outset, reducing BF by a factor of 2-5 overall, and up to an order of magnitude (e.g., from 12 to 1.2) at the beginning positions. This stark reduction helps explain why aligned models often appear less sensitive to decoding strategies. Building on this insight, we find this consistency has surprising implications for complex reasoning. Aligned Chain-of-Thought (CoT) models (e.g., DeepSeek-distilled models), for instance, leverage this effect; by generating longer reasoning chains, they push generation into later, more deterministic (lower BF) stages, resulting in more stable outputs. We hypothesize that alignment tuning does not fundamentally change a model's behavior, but instead steers it toward stylistic tokens (e.g., "Sure") that unlock low-entropy trajectories already present in the base model. This view is supported by nudging experiments, which show prompting base models with such tokens can similarly reduce BF. Together, our findings establish BF as a powerful diagnostic for understanding and controlling LLM outputs - clarifying how alignment reduces variability, how CoT promotes stable generations, and how base models can be steered away from diversity.
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AgenticSum: An Agentic Inference-Time Framework for Faithful Clinical Text Summarization

arXiv:2602.20040v1 Announce Type: cross Abstract: Large language models (LLMs) offer substantial promise for automating clinical text summarization, yet maintaining factual consistency remains challenging due to the length, noise, and heterogeneity of clinical documentation. We present AgenticSum, an inference-time, agentic framework that separates context selection, generation, verification, and targeted correction to reduce hallucinated content. The framework decomposes summarization into coordinated stages that compress task-relevant context, generate an initial draft, identify weakly supported spans using internal attention grounding signals, and selectively revise flagged content under supervisory control. We evaluate AgenticSum on two public datasets, using reference-based metrics, LLM-as-a-judge assessment, and human evaluation. Across various measures, AgenticSum demonstrates consistent improvements compared to vanilla LLMs and other strong baselines. Our results indicate that structured, agentic design with targeted correction offers an effective inference time solution to improve clinical note summarization using LLMs.
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CodePDE: An Inference Framework for LLM-driven PDE Solver Generation

arXiv:2505.08783v2 Announce Type: replace-cross Abstract: Partial differential equations (PDEs) are fundamental to modeling physical systems, yet solving them remains a complex challenge. Traditional numerical solvers rely on expert knowledge to implement and are computationally expensive, while neural-network-based solvers require large training datasets and often lack interpretability. In this work, we frame PDE solving as a code generation task and introduce CodePDE, the first inference framework for generating PDE solvers using large language models (LLMs). With CodePDE, we present a thorough evaluation on critical capacities of LLM for PDE solving: reasoning, debugging, self-refinement, and test-time scaling. CodePDE shows that, with advanced inference-time algorithms and scaling strategies, LLMs can achieve strong performance across a range of representative PDE problems. We also identify novel insights into LLM-driven solver generation, such as trade-offs between solver reliability and sophistication, design principles for LLM-powered PDE solving agents, and failure modes for LLM on hard tasks. These insights offer guidance for building more capable and reliable LLM-based scientific engines.
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