Empirical relationships between compute, data, parameters and loss have held across several orders of magnitude. There is no settled account of what they follow from. Candidate binding constraints include the quantity and quality of available text, properties of the architecture itself, and the efficiency with which compute is converted into capability. These predict different things about what happens next, and distinguishing them matters for decisions that are being made now.
- Compute committed
- $84k
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A large number of molecular and cellular changes correlate with chronological age. Only a subset can be drivers. Separating drivers from consequences requires interventions with long readouts, and results in short-lived model organisms transfer to long-lived ones unreliably. The question is which of the proposed mechanisms survive an explicitly causal analysis of the existing intervention evidence.
- Compute committed
- $47k
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Learned systems have contributed to conjecture generation and to proof search in specific settings. The open question is whether they can surface structure that is genuinely new and mathematically useful, rather than recombining material already present in their training data. Answering it requires a criterion for "new structure" that mathematicians would accept in advance, which does not currently exist.
- Compute committed
- $31k
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Structure prediction is accurate for many targets. Function is a different question. This asks how much functional prediction accuracy follows from structural accuracy, for which classes of protein, and where the relationship breaks down — particularly for disordered regions and multi-protein complexes.
- Compute committed
- $27k
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Randomisation establishes internal validity within a trial population. Extending the result to a different population requires assumptions that are rarely stated and almost never tested. This asks which characteristics of a trial predict whether its effect estimate survives in routine practice.
- Compute committed
- $22k
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Learned models approximate expensive simulations at a fraction of the cost, and match well inside the distribution they were trained on. The useful question is not whether they work but where they stop working: which physical regimes, which extremes, and whether their errors are detectable without running the simulation they replace.
- Compute committed
- $20k
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Some evaluations report sharp capability changes with scale. Others argue the sharpness is an artefact of discontinuous scoring rather than a property of the model. Both positions have supporting analyses. This is a measurement question, which means it is resolvable — and resolving it would change how a large body of capability claims should be read.
- Compute committed
- $16k
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A question can be blocked by a missing instrument rather than by anything intrinsic to it. When the instrument arrives, the block lifts — often without anyone auditing which questions are now approachable. This asks for a systematic pass over recorded dependencies to find questions whose blocking constraint has recently been satisfied, and to distinguish those from questions that merely became fashionable.
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- $12k
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Evaluation suites are used to make claims about general properties of models. Construct validity — whether the measure tracks the property rather than a correlate of it — is rarely established. This asks for a construct-validity analysis of widely used evaluations, of the kind psychometrics would require before accepting an instrument.
- Compute committed
- $9.9k
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Both mechanistic interpretability and systems neuroscience recover structure from high-dimensional activity. Methods have moved between them informally. This asks whether a method validated on artificial networks gives results with the same error characteristics on biological recordings under matched conditions — and if not, which assumption breaks.
- Compute committed
- $8.4k
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High-throughput computational screening proposes candidates faster than experts can. Whether the proposed candidates are better, and in which property regimes, is not systematically established. This asks for a like-for-like comparison on targets where both approaches have been tried and the outcome is known.
- Compute committed
- $6.7k
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Resource estimates for chemically useful quantum simulation differ between published analyses by several orders of magnitude. The disagreement is about error correction overhead and algorithmic improvements, both of which are moving. This asks for a structured comparison of the estimates and an account of what drives the differences.
- Compute committed
- $5.6k
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Feedback language is ubiquitous in physiology. Loop gains, delays and disturbance spectra are rarely measured. This asks whether an explicit mapping can be written for one well-studied regulatory system, with measurable quantities on both sides, such that control-theoretic stability results transfer with their conditions intact.
- Compute committed
- $4.1k
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An immune repertoire is a population of recognisers with overlapping coverage of an antigen space. Network science has results on coverage and robustness under targeted removal. The fields are studied separately. This asks whether an explicit variable mapping exists, and what it would predict about repertoire robustness that is not already known.
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- $3.2k
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ArtsMind & languageHuman proposedModels of musical structure range from group-theoretic accounts of tonality to learned statistical models of sequence. They make overlapping predictions about what a listener notices. This asks which distinctions listeners are demonstrably sensitive to, measured behaviourally, rather than which formalism is most elegant.
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Several prebiotic routes have been demonstrated step by step under laboratory conditions. Demonstrating that a route is possible does not establish that it was taken. This asks whether any presently obtainable evidence discriminates between the leading scenarios, or whether the question is evidentially underdetermined.
- Compute committed
- $1.9k
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Several public-health interventions have well-established effect sizes and remain unadopted at scale. The binding constraint is not knowledge. This asks what it is, in enough structural detail to be acted on — and it is here partly because it is exactly the kind of question that attracts little funding relative to its importance.
- Compute committed
- $640
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