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Runs JACKS (Joint Analysis of CRISPR/Cas9 Knockout Screens; Allen et al 2019 Genome Research) which models per-sgRNA log-fold-change as the product of a treatment-dependent gene-essentiality term and a treatment-independent guide-efficacy term. Covers the Bayesian decomposition math, the hierarchical efficacy prior shared across screens performed with the same library, when JACKS outperforms MAGeCK (multi-screen joint analysis, libraries with broad efficacy variance) and when it does not (single screen, novel libraries with no prior efficacy), library-reuse efficacy transfer, downstream essentiality interpretation, and the 2.5x sample-size reduction enabled by efficacy-aware testing. Use when running multiple screens with the same library, when guide-level noise is suspected to dominate per-gene signal, when reusing published essentiality reference screens for efficacy priors, or when comparing screens performed across cell lines that share library but differ biologically.

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Analyzes CRISPR drug-modifier (chemogenomic) screens with drugZ (Li & Hart 2019 Genome Med), a bidirectional Z-score method that identifies synthetic-lethal sensitizing genes and resistance-conferring suppressor genes from vehicle vs drug comparisons. Covers vehicle-anchored design (not Day-0), the bidirectional Z math giving 2-3x sensitivity over MAGeCK / STARS / edgeR / RIGER on drug screens, per-gene sumZ and normZ, synth (sensitizer) vs supp (suppressor) FDR, multi-dose handling, integration with control sgRNAs, and comparison with MAGeCK MLE with dose covariate. Use when running a drug-modifier CRISPR screen, identifying sensitizing or resistance genes for a drug candidate, choosing drugZ vs MAGeCK MLE for chemogenomic analysis, troubleshooting low-effect drug screens where MAGeCK lacks sensitivity, or designing a drug-screen layout (vehicle vs drug arms).

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Designs and analyzes pooled prime-editor (PE) screens for installing precise genetic variants without bystander confounding. Covers pegRNA design with PRIDICT and PRIDICT2 (Mathis 2023/2024) for predicting per-pegRNA editing efficiency, pegRNA architecture (spacer + scaffold + PBS + RTT), PE2 / PE3 / PE3b / PEmax / PEAR variants, MOSAIC in situ saturation mutagenesis (Hsu JY et al 2024 bioRxiv), the PRIME pooled-screen methodology (Erwood/Doman 2023 Nat Biotechnol 41:885; ~3,699 ClinVar variant screens), chromatin context as a primary determinant of PE efficiency, scaffold-incorporation and indel byproduct quantification with CRISPResso2, and the cross-modal validation strategy of PE + base-editor screens for variant function. Use when designing a pegRNA library for variant installation, choosing between BE and PE for a specific edit, predicting pegRNA efficiency before library synthesis, analyzing PE screen output, distinguishing intended-edit from scaffold-incorporation, or scaling PE screens to thousands of variants.

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Quantifies CRISPR editing outcomes with CRISPResso2 (Clement 2019 Nat Biotechnol) across Cas9-nuclease (indels, HDR), CBE and ABE base editors (target conversion + bystander), and prime editor (pegRNA-templated) modes. Covers single-amplicon (CRISPResso), multi-sample batch (CRISPRessoBatch), pooled-amplicon (CRISPRessoPooled), WGS off-target (CRISPRessoWGS), and sample-comparison (CRISPRessoCompare) workflows; quantification-window math that controls what is called edited; substitution-vs-indel diagnostic to distinguish BE from Cas9 contamination; MMEJ deletion pattern interpretation; allele-frequency tables; and failure modes from amplicon misalignment or contamination. Use when quantifying editing from amplicon sequencing, choosing CRISPResso mode by design, distinguishing intended edits from bystanders and indel byproducts, debugging low-alignment runs, or generating publication-grade editing reports.

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Designs and analyzes in vivo CRISPR screens in animal tumor models, organoids, and immune-cell adoptive transfers. Covers bottleneck math (250x cells/sgRNA requires ~25M cells implanted; impossible for most syngeneic models, forcing focused libraries), focused library design (Manguso 2017 Nature 547:413 immune screen; Chen 2015 tumor screens), CRISPR-StAR intrinsic-control screening (Uijttewaal 2025 Nat Biotechnol 43:1848), clonal-dynamics-limited detection, tumor-explant DNA recovery, syngeneic vs xenograft vs PDX considerations, and the relationship to downstream MAGeCK / drugZ analysis. Use when designing in vivo CRISPR screens for tumor / immune / metastasis biology, choosing focused vs genome-wide for animal models, addressing bottleneck-induced clonal collapse, picking the syngeneic / xenograft / PDX model, integrating in vivo with in vitro results, or applying CRISPR-StAR for animal experiments.

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Use this skill when the user asks about trucking rate negotiation — cost-plus pricing, market rate benchmarking via DAT/Truckstop, fuel surcharge math, how to negotiate with brokers/shippers, when to walk away, contract pricing vs spot rates. Reference DAT Rate Analytics + freight market reports.

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Use this skill when the user asks about truck purchase financing, leasing options, factoring, fuel surcharge math, lease-purchase agreements, the total-cost-of-ownership (TCO) comparison between buying + leasing, and how owner-operators finance their first truck. Cover Section 179 + Bonus Depreciation tax treatment.

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Use when a dispatcher, operations manager, or owner asks how to plan loads to minimize empty (deadhead) miles, sequence freight efficiently, balance regional capacity, design dedicated loops, or build a load-pairing strategy across customers. Covers loaded-ratio math, lane balance, region-pair pricing, and software-supported optimization.

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Search academic paper repositories (arXiv, Semantic Scholar) for scholarly articles in physics, mathematics, computer science, quantitative biology, AI/ML, and related fields

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Interactive review sessions with academic PDFs (lectures, research papers, book chapters). Extract concepts, run Q&A sessions, generate quizzes with scoring. Preserves mathematical formulas in LaTeX format. Privacy-preserving local processing - PDFs never uploaded. Use when studying academic materials, reviewing research, or preparing for exams.

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[00] TnR ABSOLUTE RIGOR — Systemic Verification Doctrine. Forced cognitive exertion for high-stakes investigations. Mandates absolute deconstruction, mathematical proof chains, and ≥95% derived certainty. Zero-tolerance for heuristics or sentiment-based reasoning. Shortcuts are defined as intentional hallucinations.

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在Python中复现C#的Quaternion.AngleAxis方法，根据角度和旋转轴计算四元数，且不使用numpy.quaternion库。

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Converts Markdown to styled HTML with WeChat-compatible themes. Supports code highlighting, math, PlantUML, footnotes, alerts, and infographics. Use when user asks for "markdown to html", "convert md to html", "md转html", or needs styled HTML output from markdown.

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Build a client invoice — "make an invoice for", "create an invoice", "bill this client for". Parses plain text into line items, computes subtotal, tax and total with the math sanity-checked.

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Generate flat, minimal light/dark-aware SVG diagrams as standalone HTML files, using a unified educational visual language with 9 semantic color ramps, sentence-case typography, and automatic dark mode. Best suited for educational and non-software visuals — physics setups, chemistry mechanisms, math curves, physical objects (aircraft, turbines, smartphones, mechanical watches), anatomy, floor plans, cross-sections, narrative journeys (lifecycle of X, process of Y), hub-spoke system integrations (smart city, IoT), and exploded layer views. If a more specialized skill exists for the subject (dedicated software/cloud architecture, hand-drawn sketches, animated explainers, etc.), prefer that — otherwise this skill can also serve as a general-purpose SVG diagram fallback with a clean educational look. Ships with 15 example diagrams.

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Manim CE animations: 3Blue1Brown math/algo videos.

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Microsoft 365 / Entra ID red-team attack chain — current 2026 reality. AADSTS code reference, user enumeration vectors (with hardening status), Smart Lockout math, Conditional Access bypass options, ROPC + SAML SSO browser flow, Burp/Playwright templates. Built from authorized red-team work where ROPC spray surfaced pre-existing lockouts and CA-blocked credentials, plus real-time external attacker activity correlation. Use for any M365/Entra credential attack, password spray, user enumeration, CA-bypass exploration, or active-attacker-detection scenario.

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Production-grade AI trading agent for cryptocurrency markets with advanced mathematical modeling, multi-layer validation, probabilistic analysis, and zero-hallucination tolerance. Implements Bayesian inference, Monte Carlo simulations, advanced risk metrics (VaR, CVaR, Sharpe), chart pattern recognition, and comprehensive cross-verification for real-world trading application.

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Audit or design server-side indexes, directories, reputations, or aggregates that are DERIVED from traffic a platform witnesses (chain heads, run verdicts, heartbeats, publish activity) so that consent gates the derivation, not merely the read: no shadow index over non-consenting principals, post-consent-only evidence windows, retention bounds and delete-propagation into derived rows, activity-oracle threat modeling, and audit-logged ranking discretion. Use when building a capability directory / whois from witnessed activity, a reputation ledger from settled outcomes, vitals aggregation across tenants, or any "the yellow pages can't lie because they index signatures" feature. Keywords: shadow index, derived index, consent gates derivation, activity oracle, phone book not a log, delist propagation, ranking weight audit, k-anonymous aggregate, subpoena surface. NOT for the consent-screen UX and scope-ladder mechanics themselves (use local-first-tenancy-boundary), reputation scoring math and Sybil economics (use agent-identity-continuity-reputation), or discovery-layer architecture L1/L2/L3 (use agent-discovery-directories-guilds).

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Builds comprehensive design systems and design bibles with production-ready CSS. Expert in design tokens, component libraries, CSS architecture. Use for design system creation, token architecture, component documentation, style guide generation. Activate on "design system", "design tokens", "CSS architecture", "component library", "style guide", "design bible". NOT for typography deep-dives (use typography-expert), color theory mathematics (use color-theory-palette-harmony-expert), brand identity strategy (use web-design-expert), or actual UI implementation (use web-design-expert or native-app-designer).

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Render mathematically-faithful Turkish marbling (Ebru) and paper-marbling with closed-form coordinate-deformation maps — a drop is a radial outward push, a comb/tine is a decaying shear, all composed as homeomorphisms over colored region boundaries. No fluid solver, runs 60fps on a 2D canvas. Use when building a marbling/Ebru toy or generative-art renderer, implementing drop/comb/wave/swirl deformations, scripting traditional patterns (Battal, Gel-Git, Şal, Bülbül Yuvası), keeping combed edges crisp via adaptive resampling, modeling ox-gall shouldering for crisp ring-in-ring drops, or exporting high-DPI marbled prints. NOT for real fluid / Navier-Stokes simulation, metaball / alpha-blended "smoke" blob effects, raster image-processing filters, or non-marbling generative art.

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Building resilient distributed systems with circuit breakers, retries with full-jitter exponential backoff, retry budgets (per-request 3-attempt + per-client 10% ratio per Google SRE), deadline propagation, and the cascading-failure math (4 layers × 3 retries = 64x amplification). Grounded in Resilience4j, Microsoft Cloud Patterns, AWS Architecture Blog (Marc Brooker), and Google SRE Book. NOT for server-side rate limiting, bulkhead isolation, backpressure protocols, or database-specific retry.

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Design and build mathematically rigorous, high-density, interactive data graphics and streaming telemetry visualizations following Mike Bostock's D3.js and Observable methodologies. Use when crafting custom SVG/Canvas charts, reactive streaming time-series, multi-dimensional brush-and-link coordinates, small multiples, or topological swarm graphs. NOT for generic dashboard template clones, basic spreadsheet charts, or off-the-shelf low-effort wrapper libraries.

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