「yc」の検索結果

Research-validated planning — research → plan → verify cycle for high-confidence implementation plans

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Diagnose and optimize timing-critical Chisel RTL for FPGA implementation while preserving cycle semantics. Use for Vivado timing bottlenecks, long ready or admission paths, queue and issue selection, free-list bank mapping, priority encoders, one-hot arbitration, wide muxes, late-arriving forwarding or override data, high-fanout controls, cross-module predicates, register-boundary changes, emitted-Verilog inspection, or routed-DCP A/B analysis. Also use when a source-level simplification needs proof that it changes timing without changing architectural state.

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Establish, author, restructure, or audit human-first processor Architecture, Design, Research, Review, and Verification documentation. Use for progressive documentation scaffolding, authority maps, reading paths, document-type content contracts, length-budgeted splitting, or maintainability reviews. Do not use as a substitute for cycle-accurate microarchitecture analysis or RTL implementation.

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Develop, challenge, and document Chisel processor microarchitecture designs before implementation. Use when discussing or writing design documents for processor pipelines, queues, issue logic, rename, ROB, LSU, caches, MSHRs, forwarding, wakeup, replay, flush, privilege, exceptions, or other cycle-accurate hardware mechanisms; when converting design conversations into stable Markdown specifications; or when reviewing a proposed Chisel CPU design for correctness, timing, area, verification cost, and cross-document consistency.

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Vehicle data through Openapi Automotive - look up cars, motorcycles, insurance and MOT status by license plate across Italy, UK, Germany, France, Spain, Portugal. Use for vehicle technical data and insurance validity checks by plate.

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Run a feature end to end — scout the code, plan it, build it, and keep a session file so a closed terminal doesn't lose the thread.

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Normalizes and transforms RNA-seq count matrices for DE, visualization, clustering, and ML. Covers between-sample (TMM, TMMwsp, RLE/median-of-ratios, upper quartile), within-sample (TPM, FPKM/RPKM), variance-stabilizing (VST, rlog, log-CPM), GC-content correction (cqn, EDASeq), and single-cell (scran deconvolution, scanpy normalize_total). Encodes the composition-bias rationale, the "most genes not DE" assumption and its catastrophic failure modes (MYC amplification, apoptosis, viral host shutoff, prokaryotic stress), the "lengthScaledTPM is not TPM" naming trap, the "TPM is not for DE" rule, the blind=TRUE vs FALSE decision, ERCC spike-in normalization (SBN), and the single-cell zero-inflation breakdown of TMM/RLE. Use when choosing or applying normalization, debugging shifted-MA-plot diagnostics, handling zero-heavy single-cell data, or correcting GC bias.

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Performs alchemical free-energy calculations including relative binding free energy (RBFE / FEP+) and absolute binding free energy (ABFE) via OpenFE, FEP+, GROMACS, AMBER pmemd, and OpenMM with explicit lambda scheduling, soft-core potentials, MBAR/BAR analysis, cycle-closure validation, and protocol-appropriate enhanced sampling. Compares ML alternatives (Boltz-2 affinity, DeepDock). Use when ranking analogs by binding affinity beyond docking accuracy, performing prospective lead optimization, or validating SAR predictions.

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Delimits putative species boundaries from molecular data within the de Queiroz 2007 unified-lineage framework using ASAP (Puillandre 2021 successor to ABGD), mPTP C++ (Kapli 2017 successor to bPTP; bPTP is Python NOT R), GMYC single/multi-threshold (Pons 2006; Fujisawa 2013), multilocus BPP v4 with prior calibration from data (NOT defaults; Yang 2015), SNAPP + BFD* for SNP delimitation, DELINEATE (Sukumaran 2021) speciation-process modeling to address Sukumaran & Knowles 2017 PNAS critique that MSC delimits structure not species, integrative-taxonomy congruence (Padial 2010; Carstens 2013), Dsuite for introgression testing before sister claims (Malinsky 2021), and Meyer & Paulay 2005 barcoding-gap-absence caveat. Use when delineating species from DNA barcoding data, resolving cryptic complexes, choosing among ASAP/mPTP/BPP/DELINEATE, calibrating BPP priors, distinguishing introgression from ILS, or applying the Sukumaran-Knowles oversplitting correction.

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Build circular genome visualizations using circlize (R), pyCirclize (Python), or Circos (Perl CLI) with ideogram tracks, multi-data tracks (scatter, histogram, heatmap), chord/link arcs for interactions, and explicit circos.clear() between plots. Covers when circular is appropriate vs when Cartesian wins (Cleveland-McGill 1984), karyograms, and chromosome adjacency in chord diagrams. Use when adjacency on the circle conveys meaning — chromosome-level overview, structural variants, Hi-C interactions, cross-genome comparisons.

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Resolve the architecture of focal oncogene amplifications — extrachromosomal DNA (ecDNA), breakage-fusion-bridge (BFB) cycles, homogeneously staining regions (HSR), and linear amplification — from whole-genome sequencing with AmpliconArchitect, the AmpliconSuite pipeline, and AmpliconClassifier. Covers copy-number seed selection, breakpoint-graph reconstruction, balanced-flow optimization, ecDNA classification, and the limits of depth-only amplification calls. Use when a focal amplification needs structural characterization, when distinguishing ecDNA from chromosomal amplification, suspecting ecDNA-driven oncogene amplification or therapy resistance, or selecting copy-number seeds for amplicon reconstruction.

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Prioritizes rare-disease variants from trio/quad WES/WGS with de novo (DeNovoGear, Triodenovo), compound-heterozygous phasing (WhatsHap), mosaic VAF tiering, phenotype-driven ranking (Exomiser, Phen2Gene, AMELIE), ClinGen gene-disease validity gating, and ACMG SF v3.2 secondary findings reporting. Use when running diagnostic exome / genome pipelines, identifying candidate Mendelian disease genes, screening for incidental findings, or auditing VUS reclassification cycles. The ACMG/AMP classification framework (PVS1 decision tree, Pejaver PP3/BP4 calibration, Tavtigian point system) is in clinical-databases/acmg-classification.

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Corrects the gene-independent copy-number artifact in CRISPR-Cas9 screens (Aguirre 2016 / Munoz 2016 Cancer Discov) where amplified loci appear essential from DNA-damage burden of simultaneous cuts. Covers the gene-independent DNA-damage / G2-arrest mechanism, CRISPRcleanR (Iorio 2018) unsupervised pre-hoc correction, CERES (Meyers 2017) joint CN + gene-effect model, Chronos (Dempster 2021) DepMap-standard population-dynamics + CN model with lowest residual bias, the decision tree by data availability, the Spearman LFC-vs-CN diagnostic, focal-amplification examples (ERBB2 in HER2+, MYC in colorectal, FGFR1 in head and neck), and CRISPRi/a alternatives that bypass the artifact. Use when screening cancer cell lines, diagnosing essentiality at amplified loci, choosing CRISPRcleanR / CERES / Chronos, deciding whether CN correction is needed before MAGeCK / BAGEL2 / drugZ, or switching from Cas9 to CRISPRi.

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Classify constitutional (germline) copy number variants for clinical reporting using the 2019 ACMG/ClinGen technical standards points-based framework, with ClassifyCNV and AnnotSV for semi-automated scoring. Covers the separate copy-number-loss and copy-number-gain rubrics, the five-tier classification, ClinGen haploinsufficiency/triplosensitivity and dosage-sensitive regions, de novo and segregation evidence, and population-frequency benign evidence. Use when assigning pathogenic/likely-pathogenic/VUS/likely-benign/benign to a constitutional CNV, scoring a CNV against ACMG/ClinGen criteria, or distinguishing the automatable evidence from the case-specific evidence requiring manual input.

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Run remote BLAST searches against NCBI servers using Biopython Bio.Blast.NCBIWWW. Use when identifying unknown sequences, finding homologs, picking the correct BLAST program (blastn/blastp/blastx/tblastn/tblastx/psiblast/megablast/dc-megablast), interpreting Karlin-Altschul E-values, avoiding the max_target_seqs trap (Shah 2019), choosing composition-based statistics, or limiting searches by organism. Covers RID lifecycle, database choice (nt/nr/refseq_select/swissprot), word-size and CBS taxonomy.

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Build automated billing systems for recurring payments, invoicing, subscription lifecycle, and dunning management. Use when implementing subscription billing, automating invoicing, or managing recurring payment systems.

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Track complex, multi-session work with dependency graphs using bd (beads) issue tracker. Use when work spans multiple sessions, has complex dependencies, or requires persistent context across compaction cycles. For simple single-session linear tasks, TodoWrite remains appropriate.

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Create irresistible offers and pitches using Alex Hormozi's methodology from $100M Offers. Guides through value equation, guarantee frameworks, pricing psychology, and creating offers "too good not to take" for any product or service.

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How to use the Adaptyv Bio Foundry API and Python SDK for protein experiment design, submission, and results retrieval. Use this skill whenever the user mentions Adaptyv, Foundry API, protein binding assays, protein screening experiments, BLI/SPR assays, thermostability assays, or wants to submit protein sequences for experimental characterization. Also trigger when code imports `adaptyv`, `adaptyv_sdk`, or `FoundryClient`, or references `foundry-api-public.adaptyvbio.com`.

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Assess whether a hospitalized adult with diabetes on insulin pump therapy remains a candidate for continued inpatient pump use. Consider triggers such as the clinician asking "Is this patient appropriate to continue insulin pump in hospital?" and evaluate for impaired consciousness, inability to adjust pump settings, critical illness, DKA, or hyperosmolar hyperglycemic state.

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Recommends CGM over SMBG for type 1 diabetes patients on multiple daily injections to reduce hypoglycemia risk. Triggered by clinician questions such as "Should I use CGM or SMBG for this T1D patient on MDI?" or "Is CGM preferred for glucose monitoring in this patient?"

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Recommends RT-CGM devices for adult patients with well-controlled type 1 diabetes who are willing and able to use the devices on a nearly daily basis. Trigger phrases include 'Controlled T1DM patient interested in CGM' and 'Consider RT-CGM for glycemic stability in well-controlled T1DM'.

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Recommends real-time CGM with confirmatory POC-BG for insulin dosing adjustments in insulin-treated hospitalized adults at high risk of hypoglycemia when resources and training are available. Triggers include: "Should we use CGM for insulin adjustments?" or "Is CGM appropriate for this patient?

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This skill suggests continuing personal CGM with or without ADIP rather than discontinuation for inpatients already using it who are at high risk for hypoglycemia. Trigger phrases include "Should I continue or discontinue personal CGM for this inpatient who is already using it?" and "Is it appropriate to maintain personal CGM during hospitalization?"

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