Designing enzyme backbones with substrate-specific functionality is a critical challenge in computational protein engineering. Current generative models excel in protein design but face limitations in binding data, substrate-specific control, and flexibility for de novo enzyme backbone generation. To address this, we introduce EnzyBind, a dataset with 11,100 experimentally validated enzyme-substrate pairs specifically curated from PDBbind. Building on this, we propose EnzyControl, a method that enables functional and substrate-specific control in enzyme backbone generation. Our approach generates enzyme backbones conditioned on MSAannotated catalytic sites and their corresponding substrates, which are automatically extracted from curated enzyme-substrate data. At the core of EnzyControl is EnzyAdapter, a lightweight, modular component integrated into a pretrained motifscaffolding model, allowing it to become substrate-aware. A two-stage training paradigm further refines the model's ability to generate accurate and functional enzyme structures. Experiments show that our EnzyControl achieves the best performance across structural and functional metrics on EnzyBind and EnzyBench benchmarks, with particularly notable improvements of 13% in designability and 13% in catalytic efficiency compared to the baseline models.

Multi-agent systems built on large language models (LLMs) require many coordination choices that are difficult to fix a priori: which skill protocol to invoke, which agent role should perform a subtask, which model to bind to each role, how roles should interact, when to use retrieval or verification, and when to omit a step entirely. These choices interact with task regime and operational constraints, so static pipelines and one-off model comparisons provide only a limited view of the design space. This paper introduces AgensFlow, an open-source framework that treats multi-agent coordination as an online policy-learning problem under partial observability. The framework makes coordination decisions observable and learnable from repeated trajectories, rather than treating skill, role, model, topology, and evaluation choices as fixed pipeline design. AgensFlow is evaluated on two corpora: distributed-systems incident tasks and security-advisory tasks. The evaluation shows three main results: learned routing reaches a higher-quality operating point than a fixed pipeline baseline on coordination-heavy classes; skip:X isolates topology compression as a meaningful part of the substrate; and warm-started policy graphs can reduce exploration cost while preserving plateau quality. Overall, the results support that learned, auditable routing can improve coordination-heavy multi-agent workflows over static wiring.

A specialized glass layer could make tomorrow's computers faster and more energy efficient. An early version of the glass substrate developed by Absolics. Human-made glass is thousands of years old. But it's now poised to find its way into the AI chips used in the world's newest and largest data centers. This year, a South Korean company called Absolics is planning to start commercial production of special glass panels designed to make next-generation computing hardware more powerful and energy efficient. Other companies, including Intel, are also pushing forward in this area.

IntroductionThe current methodologies for enzyme annotation primarily rely on established databases and classifications such as KEGG Orthology (KO), Enzyme Commission (EC) numbers, and Gene Ontology (GO) annotations, each with its specific focus and methodology. For instance, the EC system categorizes enzymes based on the chemical reactions they catalyze, providing a hierarchical numerical classification. KO links gene products to their functional orthologs across different species, whereas GO offers a broader ontology for describing the roles of genes and proteins in any organism. Despite their widespread use, these systems have notable limitations. The EC classification, while widely used, sometimes groups vastly different enzymes under the same category or subdivides similar ones excessively, based on the substrates they interact with--leading to ambiguities in enzyme function characterization.

A unified learning theory for arbitrarily fast computation with arbitrarily slow neurons

Multiplicative stochasticity such as Dropout improves the robustness and gener-alizability deep neural networks. Here, we further demonstrate that always-on multiplicative stochasticity combined with simple threshold neurons provide a sufficient substrate for deep learning machines. We call such models Neural Sampling Machines (NSM). We find that the probability of activation of the NSM exhibits a self-normalizing property that mirrors Weight Normalization, a previously studied mechanism that fulfills many of the features of Batch Normalization in an online fashion. The normalization of activities during training speeds up convergence by preventing internal covariate shift caused by changes in the distribution of inputs. The always-on stochasticity of the NSM confers the following advantages: the network is identical in the inference and learning phases, making the NSM a suitable substrate for continual learning, it can exploit stochasticity inherent to a physical substrate such as analog non-volatile memories for in memory computing, and it is suitable for Monte Carlo sampling, while requiring almost exclusively addition and comparison operations. We demonstrate NSMs on standard classification benchmarks (MNIST and CIFAR) and event-based classification benchmarks (N-MNIST and DVS Gestures). Our results show that NSMs perform comparably or better than conventional artificial neural networks with the same architecture.