substrate
The 400 million machine powering the future of chipmaking
The AI era needs ever faster chips. ASML has a monopoly on the expensive contraptions needed to pattern them. Jos Benschop is climbing a ladder to get to the top of his newest machine. The contraption is the size of a double-decker bus--more than 150 tons of gleaming precision-milled aluminum covered in thousands of snaking tubes, colored cables, and pressurized tanks. From the ground, it looks like a futuristic V8 engine. When I reach the top with Benschop we're looking down from about 15 feet in the air, with bunny-suited technicians scurrying around below. It's more than 200 cubic meters of tech--"mechatronic devices that hold a few mirrors in a position with atomic precision," he says, gesturing at the gargantuan apparatus. Benschop, a tall and grizzled 66-year-old, has spent over a decade working with his engineers to design this thing, but even so, he'll sometimes look at it and go: Benschop is the executive vice president of technology for ASML, a Dutch company that is the linchpin of the microchip industry. If you want to make powerful chips to power phones or AI, a lithography machine like the one we're standing on is what you need to create increasingly tiny circuitry. Lithography is the art and science of shining light on a silicon wafer to pattern out the transistors, wiring, and other components of the microchips that will be cut from it. The chipmaking field is essentially controlled by only two big players: ASML, which creates the lithography machines, and TSMC, the chipmaking giant. Nine years ago, ASML began selling machines that use a daring new way of patterning chip features.
EnzyControl: Adding Functional and Substrate-Specific Control for Enzyme Backbone Generation
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.
Instrumented data for causal scientific machine learning
Scientific machine learning is limited less by model size than by the data it is trained on. Observational data records what happened but not why; template synthetic data has a known generating process but only for the simulator's template, not the case a user faces. We argue a third option is now operationally feasible: instrumented data, in which every datum carries the mechanistic model that produced it, an explicit uncertainty over that model, and an executable family of counterfactuals. Verification-and-validation (V&V) instrumented image-to-simulation pipelines are one realisation: a sensor observation becomes a fully specified, solver-backed simulation with explicit, editable parameters and a propagated aleatoric/epistemic uncertainty. The substrate is case-specific, mechanistically supervised, and supports causal interventions through Pearl's do-operator.
AgensFlow: A Coordination-Policy Substrate for Multi-Agent Systems
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.
Future AI chips could be built on glass
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.
supp
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.