「designing」の検索結果

Designs covalent inhibitors and warheads targeting cysteine (most common, 98% of covalent drugs), lysine, serine, threonine, tyrosine, and aspartate residues, with explicit handling of warhead reactivity (acrylamide, chloroacetamide, vinyl sulfone, sulfonyl fluoride, fluorosulfate, aldehyde, boronate, nitrile), reversibility (kinact/Ki, t_residence), glutathione (GSH) stability, intrinsic reactivity assays, and covalent docking (DOCKovalent, GOLD, HCovDock). Use when designing covalent inhibitors for targeted covalent inhibition (TCI), KRAS G12C-style approaches, or rationalizing covalent SAR.

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Implements multiplicity control for confirmatory clinical trials using graphical procedures (Bretz-Maurer-Hommel), gatekeeping (parallel, serial, mixed), Hochberg/Hommel/Holm with PRDS, and the closed-testing principle (Marcus-Peritz-Gabriel; Goeman 2021 admissibility). Covers FDA Multiple Endpoints Final Guidance (October 2022), graphical procedures via R gMCP, primary + key-secondary + subgroup hierarchies, and FWER vs FDR distinction. Use when designing the multiplicity strategy for confirmatory trials with multiple primary or key secondary endpoints.

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Designs novel molecules using REINVENT 4 (de novo, scaffold decoration, linker design, R-group, molecular optimization), MolMIM, Diffusion-based generators (DiGress, DiffSMol), and JT-VAE with explicit handling of multi-parameter optimization (MPO), goal-directed scoring functions, transfer/reinforcement/curriculum learning, synthetic accessibility scoring, and chemical space exploration vs exploitation. Use when designing new chemical matter against a target, decorating a scaffold, linking fragments, or optimizing a hit for multiple ADMET / activity properties simultaneously.

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Designs PROTACs, molecular glues, and bivalent degraders with explicit handling of E3 ligase choice (VHL, CRBN, IAP, MDM2, KEAP1), linker design (length, composition, rigidity), ternary complex prediction (PRosettaC, DeepTernary, AlphaFold3 with constraints), cooperativity (alpha), DC50 / Dmax characterization, hook effect, and prediction-experiment reconciliation. Use when designing targeted protein degraders, planning linker SAR, predicting ternary complex stability, or building generative degrader workflows.

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Designs Bayesian clinical trials including Phase I dose-finding (BOIN, CRM, EWOC, mTPI-2), meta-analytic-predictive (MAP) priors with robust mixtures for external data borrowing, EXNEX for basket trials, hierarchical models for safety AE (Berry-Berry), Bayesian platform trials (I-SPY 2, GBM AGILE, REMAP-CAP), and posterior probability stopping rules. Covers FDA Bayesian Devices Guidance (2010), FDA Bayesian Methodology in Drugs Draft (January 2026), BOIN Fit-for-Purpose qualification (December 2021), and Project Optimus dose-optimisation. Use when designing dose-finding studies, platform trials, or sensitivity analyses with informative priors.

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Predicts whether a DNA variant alters mRNA splicing using sequence-based deep-learning tools — SpliceAI (10kb context dilated CNN, clinical default), Pangolin (multi-tissue), MMSplice (modular per-region CNN with calibrated ΔPSI), SpliceTransformer/TrASPr (tissue-aware transformers), SpliceVault (empirical 300K-RNA lookup of likely mis-splicing outcomes), CADD-Splice (composite score). Applies the ClinGen SVI 2023 framework for ACMG/AMP variant interpretation (PVS1, PP3, BP4 evidence codes), HGVS splicing nomenclature (c.123+1G>A, c.123-3T>G, r.spl?), extended-window scoring for deep-intronic pseudoexons, tissue-specific predictions, branchpoint variant detection (BPHunter, LaBranchoR), and splice-switching ASO design. Use when interpreting splice impact of clinical variants, prioritizing VUS, identifying deep-intronic pathogenic variants, or designing ASOs.

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Assesses RNA-seq data quality specifically for alternative splicing analysis. QC layers include experimental design audit (library prep, read length, depth, replicates), STAR 2-pass cohort-style alignment, junction saturation curves and discovery plateau detection, novel-vs-known junction ratio diagnostics, junction-overhang distribution, splice-site strength scoring (MaxEntScan intrinsic + SpliceAI context-aware), strandedness verification, GENCODE basic vs comprehensive choice, and rRNA contamination screening. Splicing analysis is more demanding than DGE on read length, depth, library prep, alignment strategy, and annotation choice — failures silently bias PSI estimates and inflate novel-junction false positives. Use when evaluating data suitability for splicing analysis, troubleshooting low event detection, or designing sequencing experiments where AS is a primary endpoint.

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Build and configure Laravel 10+ applications, including creating Eloquent models and relationships, implementing Sanctum authentication, configuring Horizon queues, designing RESTful APIs with API resources, and building reactive interfaces with Livewire. Use when creating Laravel models, setting up queue workers, implementing Sanctum auth flows, building Livewire components, optimising Eloquent queries, or writing Pest/PHPUnit tests for Laravel features.

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Provides expert knowledge for designing, implementing, and managing REST API versioning strategies with deprecation workflows.

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Shared vocabulary for designing deep modules. Use when the user wants to design or improve a module's interface, find deepening opportunities, decide where a seam goes, make code more testable or AI-navigable, or when another skill needs the deep-module vocabulary.

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Expert in designing and building autonomous AI agents. Masters tool use, memory systems, planning strategies, and multi-agent orchestration.

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Forces the laziest solution that actually works, simplest, shortest, most minimal. Channels a senior dev who has been paged at 3am for a factory class that wrapped one function: question whether the task needs to exist at all, reach for the standard library before custom code, native platform features before dependencies, one line before fifty. Supports intensity levels: lite, full, ultra. The default is full. Use on ANY coding task: writing, adding, refactoring, fixing, reviewing, or designing code, and choosing libraries or dependencies. Also use whenever the user says "ponytail", "be lazy", "lazy mode", "simplest solution", "minimal solution", "yagni", "do less", or "shortest path", or complains about over-engineering, bloat, boilerplate, or unnecessary dependencies. Do NOT use for non-coding requests such as general knowledge, prose, translation, summaries, recipes.

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Single Source of Truth (SSOT) guidelines for SwiftUI state management. Use when designing state architecture, choosing between @State/@Binding/@StateObject/@ObservedObject/@EnvironmentObject, fixing state synchronization issues, refactoring duplicated state, or reviewing state management in PRs. Covers SSOT principles, property wrapper selection, state lifting, and common violations.

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Core coding guidelines for iOS, iPadOS, macOS, watchOS, tvOS, and visionOS app development using SwiftUI and Swift. Use when implementing Views, working with @State/@Binding/@Observable/@StateObject, using NavigationStack/List/LazyVStack, designing components, or asking about SwiftUI patterns (infinite scroll, pull-to-refresh, search). Covers best practices, implementation patterns, and anti-patterns to avoid.

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AdwHeaderBar layout rules: button placement, flat/icon-only buttons, tooltips, title widgets, split buttons. Use when designing or fixing a GNOME app's header bar.

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Build reusable, composable, and maintainable React/Vue/Angular components following established design patterns like compound components, render props, custom hooks, and HOCs. Use when creating component libraries, implementing component composition, building reusable UI elements, designing prop APIs, managing component state patterns, implementing controlled vs uncontrolled components, creating compound components, using render props or children as functions, building custom hooks, or establishing component architecture standards.

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Design robust error handling strategies including try-catch blocks, custom error classes, error boundaries, graceful degradation, and comprehensive logging. Use when implementing exception handling, creating custom error types, setting up error boundaries in React, designing error response formats for APIs, implementing retry logic, handling async errors and promise rejections, logging errors for monitoring, creating user-friendly error messages, or building fault-tolerant systems that fail gracefully.

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Build accessible web applications following WCAG 2.1/2.2 guidelines with proper semantic HTML, ARIA attributes, keyboard navigation, screen reader support, and inclusive design. Use when implementing ARIA labels and roles, ensuring keyboard navigation, supporting screen readers, providing text alternatives for images, managing focus, creating accessible forms, building inclusive UI components, testing with accessibility tools, meeting WCAG compliance levels, or designing for users with disabilities.

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Facilitate ideation, explore alternatives, and refine concepts through structured brainstorming techniques before implementation. Use when starting new projects, designing features, exploring solutions, evaluating tradeoffs, challenging assumptions, generating creative ideas, planning architecture, or refining rough concepts into detailed designs.

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Architect scalable backend services using layered architecture, dependency injection, middleware patterns, service classes, and separation of concerns. Use when building API services, implementing business logic layers, creating service classes, setting up middleware chains, implementing dependency injection, designing controller-service-repository patterns, handling cross-cutting concerns, creating domain models, implementing CQRS patterns, or establishing backend architecture standards.

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Build real-time, reactive backend applications with Convex using TypeScript queries, mutations, and actions with automatic reactivity and optimistic updates. Use when building real-time collaborative applications, implementing reactive data synchronization, writing serverless backend functions, creating queries that auto-update, implementing mutations with transactional guarantees, handling file uploads with Convex storage, implementing authentication with Convex Auth, designing reactive database schemas, or building applications requiring instant data synchronization.

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Analyze a set of design samples (HTML mockups + website URLs) and produce a structured style guide that anchors the rest of the stardust redesign pipeline. Use when the user supplies reference designs ("design samples", "mockups", "inspiration sites", "style references") and wants to extract a consistent visual language — type system, color palette, spacing, motion, and reusable component patterns — before redesigning a target site. Triggers on phrases like "distill these samples", "extract a style guide from these examples", "use these as design references", or "analyze these mockups". Outputs a `trait-matrix.json` (structured per-sample + cross-sample design tokens) and a `SAMPLES.md` narrative brief that `stardust:direct` reads under Mode B (anchor-reference precedence) when picking a redesign direction.

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Guides ownership, borrowing, and lifetime decisions in Rust. Use when encountering E0382, E0597, E0506, E0507, move errors, or when designing data ownership.

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Guides generic vs trait object decisions in Rust. Use when choosing between static and dynamic dispatch, designing traits, handling E0277/E0038, or deciding between enum and dyn Trait.

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