@synsci/cli-darwin-x64 1.1.97 → 1.1.99

This diff represents the content of publicly available package versions that have been released to one of the supported registries. The information contained in this diff is provided for informational purposes only and reflects changes between package versions as they appear in their respective public registries.
Files changed (1549) hide show
  1. package/bin/synsc +0 -0
  2. package/package.json +1 -1
  3. package/bin/skills/accelerate/SKILL.md +0 -332
  4. package/bin/skills/accelerate/references/custom-plugins.md +0 -453
  5. package/bin/skills/accelerate/references/megatron-integration.md +0 -489
  6. package/bin/skills/accelerate/references/performance.md +0 -525
  7. package/bin/skills/adaptyv/SKILL.md +0 -114
  8. package/bin/skills/adaptyv/reference/api_reference.md +0 -308
  9. package/bin/skills/adaptyv/reference/examples.md +0 -913
  10. package/bin/skills/adaptyv/reference/experiments.md +0 -360
  11. package/bin/skills/adaptyv/reference/protein_optimization.md +0 -637
  12. package/bin/skills/aeon/SKILL.md +0 -374
  13. package/bin/skills/aeon/references/anomaly_detection.md +0 -154
  14. package/bin/skills/aeon/references/classification.md +0 -144
  15. package/bin/skills/aeon/references/clustering.md +0 -123
  16. package/bin/skills/aeon/references/datasets_benchmarking.md +0 -387
  17. package/bin/skills/aeon/references/distances.md +0 -256
  18. package/bin/skills/aeon/references/forecasting.md +0 -140
  19. package/bin/skills/aeon/references/networks.md +0 -289
  20. package/bin/skills/aeon/references/regression.md +0 -118
  21. package/bin/skills/aeon/references/segmentation.md +0 -163
  22. package/bin/skills/aeon/references/similarity_search.md +0 -187
  23. package/bin/skills/aeon/references/transformations.md +0 -246
  24. package/bin/skills/alphafold-database/SKILL.md +0 -513
  25. package/bin/skills/alphafold-database/references/api_reference.md +0 -423
  26. package/bin/skills/anndata/SKILL.md +0 -400
  27. package/bin/skills/anndata/references/best_practices.md +0 -525
  28. package/bin/skills/anndata/references/concatenation.md +0 -396
  29. package/bin/skills/anndata/references/data_structure.md +0 -314
  30. package/bin/skills/anndata/references/io_operations.md +0 -404
  31. package/bin/skills/anndata/references/manipulation.md +0 -516
  32. package/bin/skills/arboreto/SKILL.md +0 -243
  33. package/bin/skills/arboreto/references/algorithms.md +0 -138
  34. package/bin/skills/arboreto/references/basic_inference.md +0 -151
  35. package/bin/skills/arboreto/references/distributed_computing.md +0 -242
  36. package/bin/skills/arboreto/scripts/basic_grn_inference.py +0 -97
  37. package/bin/skills/astropy/SKILL.md +0 -331
  38. package/bin/skills/astropy/references/coordinates.md +0 -273
  39. package/bin/skills/astropy/references/cosmology.md +0 -307
  40. package/bin/skills/astropy/references/fits.md +0 -396
  41. package/bin/skills/astropy/references/tables.md +0 -489
  42. package/bin/skills/astropy/references/time.md +0 -404
  43. package/bin/skills/astropy/references/units.md +0 -178
  44. package/bin/skills/astropy/references/wcs_and_other_modules.md +0 -373
  45. package/bin/skills/audiocraft/SKILL.md +0 -564
  46. package/bin/skills/audiocraft/references/advanced-usage.md +0 -666
  47. package/bin/skills/audiocraft/references/troubleshooting.md +0 -504
  48. package/bin/skills/autogpt/SKILL.md +0 -403
  49. package/bin/skills/autogpt/references/advanced-usage.md +0 -535
  50. package/bin/skills/autogpt/references/troubleshooting.md +0 -420
  51. package/bin/skills/awq/SKILL.md +0 -310
  52. package/bin/skills/awq/references/advanced-usage.md +0 -324
  53. package/bin/skills/awq/references/troubleshooting.md +0 -344
  54. package/bin/skills/axolotl/SKILL.md +0 -158
  55. package/bin/skills/axolotl/references/api.md +0 -5548
  56. package/bin/skills/axolotl/references/dataset-formats.md +0 -1029
  57. package/bin/skills/axolotl/references/index.md +0 -15
  58. package/bin/skills/axolotl/references/other.md +0 -3563
  59. package/bin/skills/benchling-integration/SKILL.md +0 -480
  60. package/bin/skills/benchling-integration/references/api_endpoints.md +0 -883
  61. package/bin/skills/benchling-integration/references/authentication.md +0 -379
  62. package/bin/skills/benchling-integration/references/sdk_reference.md +0 -774
  63. package/bin/skills/bigcode-evaluation-harness/SKILL.md +0 -405
  64. package/bin/skills/bigcode-evaluation-harness/references/benchmarks.md +0 -393
  65. package/bin/skills/bigcode-evaluation-harness/references/custom-tasks.md +0 -424
  66. package/bin/skills/bigcode-evaluation-harness/references/issues.md +0 -394
  67. package/bin/skills/biopython/SKILL.md +0 -443
  68. package/bin/skills/biopython/references/advanced.md +0 -577
  69. package/bin/skills/biopython/references/alignment.md +0 -362
  70. package/bin/skills/biopython/references/blast.md +0 -455
  71. package/bin/skills/biopython/references/databases.md +0 -484
  72. package/bin/skills/biopython/references/phylogenetics.md +0 -566
  73. package/bin/skills/biopython/references/sequence_io.md +0 -285
  74. package/bin/skills/biopython/references/structure.md +0 -564
  75. package/bin/skills/biorxiv-database/SKILL.md +0 -483
  76. package/bin/skills/biorxiv-database/references/api_reference.md +0 -280
  77. package/bin/skills/biorxiv-database/scripts/biorxiv_search.py +0 -445
  78. package/bin/skills/bioservices/SKILL.md +0 -361
  79. package/bin/skills/bioservices/references/identifier_mapping.md +0 -685
  80. package/bin/skills/bioservices/references/services_reference.md +0 -636
  81. package/bin/skills/bioservices/references/workflow_patterns.md +0 -811
  82. package/bin/skills/bioservices/scripts/batch_id_converter.py +0 -347
  83. package/bin/skills/bioservices/scripts/compound_cross_reference.py +0 -378
  84. package/bin/skills/bioservices/scripts/pathway_analysis.py +0 -309
  85. package/bin/skills/bioservices/scripts/protein_analysis_workflow.py +0 -408
  86. package/bin/skills/bitsandbytes/SKILL.md +0 -411
  87. package/bin/skills/bitsandbytes/references/memory-optimization.md +0 -521
  88. package/bin/skills/bitsandbytes/references/qlora-training.md +0 -521
  89. package/bin/skills/bitsandbytes/references/quantization-formats.md +0 -447
  90. package/bin/skills/blip-2/SKILL.md +0 -564
  91. package/bin/skills/blip-2/references/advanced-usage.md +0 -680
  92. package/bin/skills/blip-2/references/troubleshooting.md +0 -526
  93. package/bin/skills/brenda-database/SKILL.md +0 -719
  94. package/bin/skills/brenda-database/references/api_reference.md +0 -537
  95. package/bin/skills/brenda-database/scripts/brenda_queries.py +0 -844
  96. package/bin/skills/brenda-database/scripts/brenda_visualization.py +0 -772
  97. package/bin/skills/brenda-database/scripts/enzyme_pathway_builder.py +0 -1053
  98. package/bin/skills/cellxgene-census/SKILL.md +0 -511
  99. package/bin/skills/cellxgene-census/references/census_schema.md +0 -182
  100. package/bin/skills/cellxgene-census/references/common_patterns.md +0 -351
  101. package/bin/skills/chembl-database/SKILL.md +0 -389
  102. package/bin/skills/chembl-database/references/api_reference.md +0 -272
  103. package/bin/skills/chembl-database/scripts/example_queries.py +0 -278
  104. package/bin/skills/chroma/SKILL.md +0 -406
  105. package/bin/skills/chroma/references/integration.md +0 -38
  106. package/bin/skills/cirq/SKILL.md +0 -346
  107. package/bin/skills/cirq/references/building.md +0 -307
  108. package/bin/skills/cirq/references/experiments.md +0 -572
  109. package/bin/skills/cirq/references/hardware.md +0 -515
  110. package/bin/skills/cirq/references/noise.md +0 -515
  111. package/bin/skills/cirq/references/simulation.md +0 -350
  112. package/bin/skills/cirq/references/transformation.md +0 -416
  113. package/bin/skills/citation-management/SKILL.md +0 -1109
  114. package/bin/skills/citation-management/assets/bibtex_template.bib +0 -264
  115. package/bin/skills/citation-management/assets/citation_checklist.md +0 -386
  116. package/bin/skills/citation-management/references/bibtex_formatting.md +0 -908
  117. package/bin/skills/citation-management/references/citation_validation.md +0 -794
  118. package/bin/skills/citation-management/references/google_scholar_search.md +0 -725
  119. package/bin/skills/citation-management/references/metadata_extraction.md +0 -870
  120. package/bin/skills/citation-management/references/pubmed_search.md +0 -839
  121. package/bin/skills/citation-management/scripts/doi_to_bibtex.py +0 -182
  122. package/bin/skills/citation-management/scripts/extract_metadata.py +0 -570
  123. package/bin/skills/citation-management/scripts/format_bibtex.py +0 -349
  124. package/bin/skills/citation-management/scripts/search_google_scholar.py +0 -251
  125. package/bin/skills/citation-management/scripts/search_pubmed.py +0 -348
  126. package/bin/skills/citation-management/scripts/validate_citations.py +0 -494
  127. package/bin/skills/clinical-decision-support/README.md +0 -129
  128. package/bin/skills/clinical-decision-support/SKILL.md +0 -506
  129. package/bin/skills/clinical-decision-support/assets/biomarker_report_template.tex +0 -380
  130. package/bin/skills/clinical-decision-support/assets/clinical_pathway_template.tex +0 -222
  131. package/bin/skills/clinical-decision-support/assets/cohort_analysis_template.tex +0 -359
  132. package/bin/skills/clinical-decision-support/assets/color_schemes.tex +0 -149
  133. package/bin/skills/clinical-decision-support/assets/example_gbm_cohort.md +0 -208
  134. package/bin/skills/clinical-decision-support/assets/recommendation_strength_guide.md +0 -328
  135. package/bin/skills/clinical-decision-support/assets/treatment_recommendation_template.tex +0 -529
  136. package/bin/skills/clinical-decision-support/references/biomarker_classification.md +0 -719
  137. package/bin/skills/clinical-decision-support/references/clinical_decision_algorithms.md +0 -604
  138. package/bin/skills/clinical-decision-support/references/evidence_synthesis.md +0 -840
  139. package/bin/skills/clinical-decision-support/references/outcome_analysis.md +0 -640
  140. package/bin/skills/clinical-decision-support/references/patient_cohort_analysis.md +0 -427
  141. package/bin/skills/clinical-decision-support/references/treatment_recommendations.md +0 -521
  142. package/bin/skills/clinical-decision-support/scripts/biomarker_classifier.py +0 -383
  143. package/bin/skills/clinical-decision-support/scripts/build_decision_tree.py +0 -417
  144. package/bin/skills/clinical-decision-support/scripts/create_cohort_tables.py +0 -509
  145. package/bin/skills/clinical-decision-support/scripts/generate_survival_analysis.py +0 -441
  146. package/bin/skills/clinical-decision-support/scripts/validate_cds_document.py +0 -326
  147. package/bin/skills/clinical-reports/IMPLEMENTATION_SUMMARY.md +0 -641
  148. package/bin/skills/clinical-reports/README.md +0 -236
  149. package/bin/skills/clinical-reports/SKILL.md +0 -1127
  150. package/bin/skills/clinical-reports/assets/case_report_template.md +0 -352
  151. package/bin/skills/clinical-reports/assets/clinical_trial_csr_template.md +0 -353
  152. package/bin/skills/clinical-reports/assets/clinical_trial_sae_template.md +0 -359
  153. package/bin/skills/clinical-reports/assets/consult_note_template.md +0 -305
  154. package/bin/skills/clinical-reports/assets/discharge_summary_template.md +0 -453
  155. package/bin/skills/clinical-reports/assets/hipaa_compliance_checklist.md +0 -395
  156. package/bin/skills/clinical-reports/assets/history_physical_template.md +0 -305
  157. package/bin/skills/clinical-reports/assets/lab_report_template.md +0 -309
  158. package/bin/skills/clinical-reports/assets/pathology_report_template.md +0 -249
  159. package/bin/skills/clinical-reports/assets/quality_checklist.md +0 -338
  160. package/bin/skills/clinical-reports/assets/radiology_report_template.md +0 -318
  161. package/bin/skills/clinical-reports/assets/soap_note_template.md +0 -253
  162. package/bin/skills/clinical-reports/references/case_report_guidelines.md +0 -570
  163. package/bin/skills/clinical-reports/references/clinical_trial_reporting.md +0 -693
  164. package/bin/skills/clinical-reports/references/data_presentation.md +0 -530
  165. package/bin/skills/clinical-reports/references/diagnostic_reports_standards.md +0 -629
  166. package/bin/skills/clinical-reports/references/medical_terminology.md +0 -588
  167. package/bin/skills/clinical-reports/references/patient_documentation.md +0 -744
  168. package/bin/skills/clinical-reports/references/peer_review_standards.md +0 -585
  169. package/bin/skills/clinical-reports/references/regulatory_compliance.md +0 -577
  170. package/bin/skills/clinical-reports/scripts/check_deidentification.py +0 -332
  171. package/bin/skills/clinical-reports/scripts/compliance_checker.py +0 -78
  172. package/bin/skills/clinical-reports/scripts/extract_clinical_data.py +0 -97
  173. package/bin/skills/clinical-reports/scripts/format_adverse_events.py +0 -97
  174. package/bin/skills/clinical-reports/scripts/generate_report_template.py +0 -149
  175. package/bin/skills/clinical-reports/scripts/terminology_validator.py +0 -126
  176. package/bin/skills/clinical-reports/scripts/validate_case_report.py +0 -323
  177. package/bin/skills/clinical-reports/scripts/validate_trial_report.py +0 -88
  178. package/bin/skills/clinicaltrials-database/SKILL.md +0 -507
  179. package/bin/skills/clinicaltrials-database/references/api_reference.md +0 -358
  180. package/bin/skills/clinicaltrials-database/scripts/query_clinicaltrials.py +0 -215
  181. package/bin/skills/clinpgx-database/SKILL.md +0 -638
  182. package/bin/skills/clinpgx-database/references/api_reference.md +0 -757
  183. package/bin/skills/clinpgx-database/scripts/query_clinpgx.py +0 -518
  184. package/bin/skills/clinvar-database/SKILL.md +0 -362
  185. package/bin/skills/clinvar-database/references/api_reference.md +0 -227
  186. package/bin/skills/clinvar-database/references/clinical_significance.md +0 -218
  187. package/bin/skills/clinvar-database/references/data_formats.md +0 -358
  188. package/bin/skills/clip/SKILL.md +0 -253
  189. package/bin/skills/clip/references/applications.md +0 -207
  190. package/bin/skills/cobrapy/SKILL.md +0 -463
  191. package/bin/skills/cobrapy/references/api_quick_reference.md +0 -655
  192. package/bin/skills/cobrapy/references/workflows.md +0 -593
  193. package/bin/skills/colab-finetuning/SKILL.md +0 -153
  194. package/bin/skills/colab-finetuning/references/bridge-setup.md +0 -68
  195. package/bin/skills/colab-finetuning/references/gpu-tiers.md +0 -54
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  197. package/bin/skills/constitutional-ai/SKILL.md +0 -290
  198. package/bin/skills/cosmic-database/SKILL.md +0 -336
  199. package/bin/skills/cosmic-database/references/cosmic_data_reference.md +0 -220
  200. package/bin/skills/cosmic-database/scripts/download_cosmic.py +0 -231
  201. package/bin/skills/crewai/SKILL.md +0 -498
  202. package/bin/skills/crewai/references/flows.md +0 -438
  203. package/bin/skills/crewai/references/tools.md +0 -429
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  205. package/bin/skills/dask/SKILL.md +0 -456
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  209. package/bin/skills/dask/references/dataframes.md +0 -368
  210. package/bin/skills/dask/references/futures.md +0 -541
  211. package/bin/skills/dask/references/schedulers.md +0 -504
  212. package/bin/skills/datacommons-client/SKILL.md +0 -255
  213. package/bin/skills/datacommons-client/references/getting_started.md +0 -417
  214. package/bin/skills/datacommons-client/references/node.md +0 -250
  215. package/bin/skills/datacommons-client/references/observation.md +0 -185
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  217. package/bin/skills/datamol/SKILL.md +0 -706
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  224. package/bin/skills/deepchem/SKILL.md +0 -597
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  227. package/bin/skills/deepchem/scripts/graph_neural_network.py +0 -338
  228. package/bin/skills/deepchem/scripts/predict_solubility.py +0 -224
  229. package/bin/skills/deepchem/scripts/transfer_learning.py +0 -375
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- # NIH Specific Aims Page: The Complete Guide
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- ## Overview
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- The **Specific Aims page** is the most important page of your entire NIH grant application. It's the first thing reviewers read, often determines their initial impression, and may be the only page read by some panel members before scoring begins.
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- **Length**: Exactly 1 page
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- **Margins**: 0.5 inches (all sides)
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- **Font**: 11-point Arial, Helvetica, or similar (no smaller)
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- **Line spacing**: Must be readable
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- **Purpose**:
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- - Communicate your research vision clearly and compellingly
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- - Establish significance and innovation
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- - Demonstrate feasibility
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- - Show that you can accomplish meaningful work in the proposed timeframe
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- - Make reviewers excited to fund your work
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- ## Anatomy of a Specific Aims Page
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- ### Essential Components (in order)
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- 1. **Opening Hook** (2-4 sentences)
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- 2. **Gap/Problem Statement** (2-4 sentences)
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- 3. **Long-Term Goal** (1 sentence)
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- 4. **Objective** (1-2 sentences)
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- 5. **Central Hypothesis** (1 sentence) [or Research Questions]
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- 6. **Rationale** (2-3 sentences with preliminary data mention)
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- 7. **Specific Aims** (2-4 aims, ~½ page total)
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- 8. **Expected Outcomes and Impact** (2-4 sentences)
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- ## Detailed Structure
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- ### Opening Paragraph: The Hook
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- **Purpose**: Establish importance and grab attention
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- **What to include**:
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- - Broad context (disease burden, biological importance, technological need)
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- - Epidemiological data or statistics that establish scale
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- - Why this problem matters for health or science
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- - Create urgency
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- **Length**: 2-4 sentences
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- **Writing tips**:
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- - Start strong with compelling statement
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- - Use concrete numbers (prevalence, mortality, costs)
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- - Avoid jargon in first sentence
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- - Make it accessible to non-specialists on panel
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- **Examples**:
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- *Clinical Example*:
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- "Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer death in the United States, with a devastating 5-year survival rate of only 11%. Despite decades of research, therapeutic options remain limited, and most patients present with advanced, unresectable disease. The lack of effective early detection methods and targeted therapies represents a critical unmet medical need affecting over 62,000 Americans diagnosed annually."
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- *Basic Science Example*:
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- "Mitochondrial dysfunction is a hallmark of aging and age-related diseases, yet the mechanisms linking mitochondrial decline to cellular senescence remain poorly understood. Emerging evidence suggests that mitochondrial-nuclear communication pathways play a central role in longevity determination across species, from yeast to mammals. Understanding how cells sense and respond to mitochondrial stress could reveal new therapeutic targets for age-related diseases affecting millions worldwide."
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- ### Second Paragraph: Gap and Context
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- **Purpose**: Define what's known, what's unknown, and why it matters
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- **What to include**:
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- - Current state of knowledge (brief literature context)
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- - Specific gap or barrier to progress
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- - Why this gap is critical to address
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- - Why current approaches are insufficient
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- **Length**: 3-5 sentences
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- **Structure**:
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- 1. What we know (1-2 sentences)
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- 2. What we don't know / what's limiting progress (1-2 sentences)
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- **Examples**:
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- "Prior studies have identified numerous genetic mutations associated with PDAC development, including KRAS, TP53, SMAD4, and CDKN2A. However, the tumor microenvironment (TME), comprising immune cells, fibroblasts, and extracellular matrix, is increasingly recognized as a critical determinant of therapeutic resistance. Current models fail to recapitulate the complex TME architecture and cell-cell interactions that drive therapy resistance in vivo, limiting our ability to develop effective treatments. Understanding how the TME protects tumor cells from chemotherapy is essential for designing combination therapies that overcome resistance."
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- ### Third Paragraph: Long-Term Goal, Objective, Hypothesis, Rationale
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- **Purpose**: Set up your specific approach and justification
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- **Structure**:
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- **Long-Term Goal** (1 sentence):
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- - Your overarching research program direction
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- - Broader than this specific proposal
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- *Example*: "The long-term goal of our research is to elucidate the molecular mechanisms by which the tumor microenvironment promotes therapeutic resistance in pancreatic cancer."
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- **Objective** (1-2 sentences):
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- - Specific objective of THIS grant
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- - What you will accomplish in 3-5 years
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- - More focused than long-term goal
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- *Example*: "The objective of this application is to define the role of cancer-associated fibroblasts (CAFs) in mediating gemcitabine resistance and to develop combination therapies targeting CAF-tumor interactions."
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- **Central Hypothesis** (1 sentence):
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- - Testable prediction
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- - Should unify the specific aims
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- - Based on preliminary data or logical reasoning
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- - Clear and specific
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- *Example*: "Our central hypothesis is that CAF-secreted factors activate protective autophagy in tumor cells, conferring resistance to gemcitabine, and that dual inhibition of CAF signaling and autophagy will restore drug sensitivity."
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- **Alternative: Research Questions** (if hypothesis-testing isn't appropriate):
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- - 2-3 focused questions
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- - Should correspond to specific aims
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- *Example*: "This project will address the following questions: (1) What factors secreted by CAFs promote tumor cell survival during chemotherapy? (2) How do tumor cells integrate CAF signals to activate protective responses? (3) Can targeting CAF-tumor interactions enhance therapeutic efficacy in preclinical models?"
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- **Rationale** (2-3 sentences):
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- - Why you think the hypothesis is true
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- - Mention key preliminary data (very briefly)
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- - Logical basis for your approach
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- - Why this approach will work
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- *Example*: "This hypothesis is based on our preliminary data showing that CAF-conditioned medium protects tumor cells from gemcitabine-induced apoptosis by 60% (Fig. 1), and that this protection is blocked by autophagy inhibitors (Fig. 2). Proteomic analysis of CAF secretomes identified 15 candidate factors enriched in drug-resistant contexts (Table 1). These findings suggest a targetable pathway linking CAF signaling to tumor cell survival that could be exploited therapeutically."
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- ### Specific Aims (Main Section)
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- **How many aims**: 2-4 aims (3 is most common for R01)
126
- - **Too few (1)**: Insufficient work, appears risky
127
- - **Just right (2-3)**: Focused, achievable, synergistic
128
- - **Too many (4+)**: Overly ambitious, unlikely to complete
129
-
130
- **Structure for each aim**:
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- 1. **Aim Statement** (1-2 sentences, bold or underlined)
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- 2. **Rationale and Background** (1-3 sentences)
133
- 3. **Working Hypothesis** (1 sentence, if applicable)
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- 4. **Approach Summary** (2-4 sentences)
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- 5. **Expected Outcomes and Interpretation** (1-2 sentences)
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- **Length per aim**: ~4-6 sentences (¼ to ⅓ page)
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-
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- **Relationships between aims**:
140
- - **Independent**: Failure of one aim doesn't doom the others
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- - **Synergistic**: Aims build on each other or address complementary questions
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- - **Progressive**: Aim 1 enables Aim 2, Aim 2 enables Aim 3 (be careful—creates risk)
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-
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- #### Example Aim Structure:
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- **Aim 1: Identify CAF-secreted factors that mediate gemcitabine resistance.**
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- *Rationale*: CAF-conditioned medium confers significant protection against gemcitabine (Fig. 1), suggesting secreted factors are responsible. We have identified 15 candidate proteins enriched in CAF secretomes from resistant versus sensitive contexts (Table 1).
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- *Working Hypothesis*: CAFs secrete specific growth factors and cytokines (including IL-6, CXCL12, and HGF) that activate pro-survival pathways in tumor cells.
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- *Approach*: We will (1) validate candidate factors using neutralizing antibodies in co-culture assays, (2) measure activation of downstream signaling pathways (STAT3, PI3K/AKT, MAPK) in tumor cells, and (3) perform CRISPR screens in CAFs to identify factors required for resistance phenotype. We will use patient-derived CAFs and tumor cells to ensure clinical relevance.
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-
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- *Expected Outcomes*: We expect to identify 3-5 CAF-secreted factors sufficient and necessary for gemcitabine resistance, and define their signaling mechanisms. These will serve as therapeutic targets for Aims 2-3.
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-
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- ---
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-
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- **Aim 2: Determine the mechanisms by which CAF signals activate protective autophagy in tumor cells.**
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-
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- *Rationale*: Our data show that CAF-mediated resistance requires autophagy (Fig. 2), but the signaling pathways linking CAF factors to autophagy activation remain unknown.
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-
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- *Working Hypothesis*: CAF-secreted factors activate mTOR-independent autophagy through AMPK and ULK1 phosphorylation.
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-
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- *Approach*: We will (1) measure autophagy flux in tumor cells exposed to CAF factors using LC3 turnover assays and electron microscopy, (2) define signaling pathways using phosphoproteomic analysis and pharmacologic inhibitors, and (3) validate pathways using genetic knockdowns (shRNA/CRISPR) of key nodes. Studies will be performed in 2D and 3D co-culture systems.
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-
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- *Expected Outcomes*: We will define the signaling cascade from CAF factors to autophagy activation, identifying druggable nodes for combination therapy. Results will inform Aim 3 therapeutic strategies.
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-
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- ---
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-
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- **Aim 3: Evaluate combination therapies targeting CAF-tumor interactions in preclinical models.**
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-
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- *Rationale*: Single-agent therapies targeting CAFs or autophagy have shown limited efficacy clinically, suggesting combination approaches are needed.
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-
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- *Working Hypothesis*: Dual inhibition of CAF signaling and autophagy will synergistically restore gemcitabine sensitivity in vivo.
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-
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- *Approach*: Using patient-derived xenograft (PDX) models and genetically engineered mouse models (GEMM) of PDAC, we will test combinations of (1) gemcitabine + CAF pathway inhibitors identified in Aim 1, (2) gemcitabine + autophagy inhibitors, and (3) triple combinations. We will assess tumor growth, survival, and mechanism (IHC, RNA-seq) in n=10-15 mice per group.
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- *Expected Outcomes*: We expect combination therapies will reduce tumor growth by ≥60% compared to gemcitabine alone, with synergistic effects. The most effective regimen will be advanced toward clinical translation through an investigator-initiated trial (we have IND-enabling resources available at our institution).
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-
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- ### Closing Paragraph: Impact and Significance
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-
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- **Purpose**: Leave reviewers with enthusiasm and clear understanding of importance
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-
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- **What to include**:
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- - Expected outcomes of the overall project
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- - How findings will advance the field
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- - Positive impact on health or science
188
- - Next steps or future directions
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- - Why this matters
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-
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- **Length**: 2-4 sentences
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-
193
- **Writing tips**:
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- - Be confident but not arrogant
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- - Connect back to opening (full circle)
196
- - Emphasize transformative potential
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- - Avoid over-promising
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-
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- **Examples**:
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-
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- "The proposed research is significant because it will define a novel mechanism of chemotherapy resistance in pancreatic cancer and identify new therapeutic targets to overcome this resistance. Results will provide mechanistic insights into CAF-tumor interactions that drive drug resistance, immediately applicable to clinical trial design. We expect findings will enable rational design of combination therapies that improve outcomes for PDAC patients, who currently have few effective treatment options. This work will establish new paradigms for targeting the tumor microenvironment in solid cancers."
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-
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- ## Writing Principles
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-
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- ### Clarity and Accessibility
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-
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- **Write for a mixed audience**:
208
- - Some panel members will be experts in your area
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- - Others will be in related but not identical fields
210
- - Program officers and council members will read it
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- - Some reviewers will only read this page before scoring
212
-
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- **Strategies**:
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- - Define technical terms at first use
215
- - Explain abbreviations (except very common ones)
216
- - Use clear, direct language
217
- - Avoid excessive jargon
218
- - Make logical flow obvious
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-
220
- ### Confidence Without Arrogance
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-
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- **Confident** ✅:
223
- - "Our preliminary data demonstrate..."
224
- - "We have established a robust model system..."
225
- - "This approach will elucidate..."
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-
227
- **Arrogant** ❌:
228
- - "We are uniquely qualified..."
229
- - "Only our lab can do this..."
230
- - "This will revolutionize the field..."
231
-
232
- **Tentative** ❌:
233
- - "We hope to..."
234
- - "We will try to..."
235
- - "It is possible that..."
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-
237
- ### Active and Specific
238
-
239
- **Aim statements should**:
240
- - Start with action verbs (Determine, Identify, Elucidate, Define, Characterize, Validate, Develop)
241
- - Be specific and testable
242
- - Indicate what will be learned
243
-
244
- **Weak Aim** ❌:
245
- "Aim 1: Study the role of protein X in disease Y"
246
-
247
- **Strong Aim** ✅:
248
- "Aim 1: Determine how protein X phosphorylation regulates disease Y progression using genetic and pharmacologic approaches"
249
-
250
- ### Show Feasibility
251
-
252
- **Throughout the aims page**:
253
- - Mention preliminary data (figures, tables)
254
- - Reference established methods
255
- - Show you have necessary resources
256
- - Demonstrate expertise
257
- - Indicate prior success
258
-
259
- **Don't**:
260
- - Relegate all preliminary data to Research Strategy
261
- - Make it seem like you're starting from scratch
262
- - Propose overly ambitious aims without support
263
-
264
- ## Common Mistakes
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-
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- ### Mistake 1: Too Much Background
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-
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- ❌ Half page of background before getting to aims
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-
270
- ✅ Focused background that motivates your specific approach
271
-
272
- The aims page is NOT a mini review article. Provide only enough background to establish importance and gaps.
273
-
274
- ### Mistake 2: Vague Objectives
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-
276
- ❌ "We will study the mechanisms of disease X"
277
- ❌ "We will investigate the role of protein Y"
278
-
279
- ✅ "We will identify the phosphorylation sites on protein Y that regulate its interaction with Z using mass spectrometry and mutagenesis"
280
-
281
- ### Mistake 3: Overly Ambitious Scope
282
-
283
- ❌ Four aims, each of which could be a separate R01
284
- ❌ Proposing to solve multiple major questions in the field
285
- ❌ "Boil the ocean" approach
286
-
287
- ✅ Focused aims that are clearly achievable in 3-5 years
288
-
289
- ### Mistake 4: Dependent Aims
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-
291
- ❌ Aim 2 and Aim 3 both require Aim 1 to succeed
292
-
293
- ✅ Aims are synergistic but independent (failure of one doesn't doom the others)
294
-
295
- ### Mistake 5: No Preliminary Data Mentioned
296
-
297
- ❌ Seems like a fishing expedition
298
- ❌ Reviewers wonder if it's feasible
299
-
300
- ✅ Brief mentions of preliminary data throughout (refer to figures)
301
-
302
- ### Mistake 6: Weak Impact Statement
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-
304
- ❌ "This will advance our understanding of X"
305
- ❌ "Results will be published and presented"
306
-
307
- ✅ "This will identify new therapeutic targets for disease X, affecting 500,000 patients annually, and provide the foundation for investigator-initiated clinical trials"
308
-
309
- ### Mistake 7: Jargon-Heavy First Paragraph
310
-
311
- ❌ Opening sentence full of abbreviations and specialized terminology
312
- ❌ Assumes all reviewers are experts in your subfield
313
-
314
- ✅ Opening that's comprehensible to broad scientific audience
315
-
316
- ### Mistake 8: No Clear Hypothesis
317
-
318
- ❌ Just listing aims without unifying framework
319
- ❌ Purely descriptive aims
320
-
321
- ✅ Clear, testable hypothesis that unifies the aims
322
-
323
- ### Mistake 9: Forgetting Page Limits
324
-
325
- ❌ Using 1.1 pages (will be deleted or rejected)
326
- ❌ Tiny fonts to cram in more content (violations)
327
-
328
- ✅ Exactly 1 page with compliant formatting
329
-
330
- ### Mistake 10: Not Telling a Story
331
-
332
- ❌ Disconnected aims that feel like 3 separate projects
333
- ❌ No logical flow or coherence
334
-
335
- ✅ Unified narrative with aims building on each other
336
-
337
- ## Advanced Tips
338
-
339
- ### Use Visual Elements
340
-
341
- **Figures on Specific Aims Page**:
342
- - NIH allows figures on aims page
343
- - Can be very effective to show key preliminary data
344
- - Must be legible (font size requirements apply)
345
- - Don't let figure crowd out text
346
- - Typical: 1 small figure or panel showing most critical data
347
-
348
- **Tables**:
349
- - Can summarize preliminary data compactly
350
- - Show patient characteristics, gene lists, etc.
351
- - Must be readable
352
-
353
- ### Strategic Use of Bold/Italics
354
-
355
- **Appropriate**:
356
- - Bold aim statements to make them stand out
357
- - Italicize gene names (standard convention)
358
- - Underline key points (sparingly)
359
-
360
- **Avoid**:
361
- - Excessive formatting that looks cluttered
362
- - All caps (looks like shouting)
363
- - Colors (may not print/display correctly)
364
-
365
- ### The "Skim Test"
366
-
367
- **Your aims page should pass the skim test**:
368
- - Someone reading just aim statements should understand the project
369
- - Bold aim statements that can be read independently
370
- - Each paragraph has clear topic sentence
371
- - Logical flow is apparent even when skimming
372
-
373
- **Exercise**: Ask colleague to read only bold/underlined text—can they understand the project?
374
-
375
- ### Tailoring to Career Stage
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-
377
- **Early Stage Investigators**:
378
- - Show you've thought through challenges
379
- - Demonstrate strong mentorship and institutional support
380
- - Emphasize innovation while ensuring feasibility
381
- - Don't over-promise
382
-
383
- **Established Investigators**:
384
- - Show how this extends your research program
385
- - Emphasize track record implicitly
386
- - Can propose more ambitious aims if supported by extensive preliminary data
387
- - Show how this opens new directions
388
-
389
- ## Examples of Strong Opening Paragraphs
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-
391
- ### Example 1: Cancer Biology
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-
393
- "Metastatic breast cancer kills over 42,000 women annually in the United States, with median survival of only 2-3 years after diagnosis. While primary tumors are often curable, metastatic disease remains incurable due to therapy resistance and tumor heterogeneity. The emergence of drug-resistant cell populations during treatment represents the major barrier to long-term survival, yet the mechanisms governing resistance evolution remain poorly understood. Understanding how tumor heterogeneity and plasticity drive resistance could reveal new therapeutic strategies to prevent or reverse treatment failure."
394
-
395
- ### Example 2: Neuroscience
396
-
397
- "Alzheimer's disease (AD) affects 6.7 million Americans and is projected to reach 13 million by 2050, with annual costs exceeding $355 billion. Despite decades of research focused on amyloid-β and tau pathologies, no disease-modifying therapies exist. Emerging evidence implicates synaptic dysfunction as the earliest pathological event in AD, preceding neurodegeneration by years. The molecular mechanisms linking synaptic failure to cognitive decline represent a critical therapeutic window, yet remain poorly defined. Identifying early synaptic alterations could enable intervention before irreversible neuronal loss occurs."
398
-
399
- ### Example 3: Infectious Disease
400
-
401
- "Antimicrobial-resistant (AMR) infections cause over 2.8 million illnesses and 35,000 deaths annually in the US, with healthcare costs exceeding $4.6 billion. Carbapenem-resistant Enterobacterales (CRE) represent an urgent threat, with mortality rates exceeding 50% for bloodstream infections. Despite this crisis, only two new antibiotics targeting CRE have been approved in the past decade, both with significant limitations. Novel therapeutic approaches that bypass traditional antibiotic mechanisms are urgently needed to combat this growing threat. Targeting host-pathogen interactions rather than bacterial viability represents a promising strategy to combat AMR while reducing selection pressure for resistance."
402
-
403
- ## Revision Checklist
404
-
405
- Before finalizing, ensure your aims page:
406
-
407
- **Content**:
408
- - [ ] Opens with compelling statement of importance
409
- - [ ] Clearly defines the gap or problem
410
- - [ ] States specific, measurable objective
411
- - [ ] Presents testable hypothesis (or focused research questions)
412
- - [ ] Mentions preliminary data supporting feasibility
413
- - [ ] Includes 2-4 specific aims
414
- - [ ] Each aim is testable and achievable
415
- - [ ] Aims are independent but synergistic
416
- - [ ] Expected outcomes are clearly stated
417
- - [ ] Closes with impact and significance
418
-
419
- **Clarity**:
420
- - [ ] First paragraph is accessible to non-specialists
421
- - [ ] Technical terms are defined
422
- - [ ] Abbreviations are spelled out at first use
423
- - [ ] Logical flow is clear
424
- - [ ] Aim statements can stand alone
425
- - [ ] Language is confident and active
426
-
427
- **Format**:
428
- - [ ] Exactly 1 page
429
- - [ ] 0.5-inch margins
430
- - [ ] 11-point font or larger
431
- - [ ] Readable line spacing
432
- - [ ] Compliant with NIH formatting requirements
433
- - [ ] Figures (if included) are legible
434
-
435
- **Impact**:
436
- - [ ] Passes the "skim test"
437
- - [ ] Would make you excited if you were a reviewer
438
- - [ ] Clearly articulates significance
439
- - [ ] Shows feasibility without over-selling
440
- - [ ] Connects to health or scientific impact
441
-
442
- ## Final Thoughts
443
-
444
- The Specific Aims page is where grants are won or lost. **Invest time in getting this right**:
445
-
446
- - Write 10+ drafts
447
- - Get feedback from colleagues and mentors
448
- - Test it on people outside your field
449
- - Read it aloud to check flow
450
- - Let it sit, then revise with fresh eyes
451
- - Study funded examples in your field
452
-
453
- **Remember**: Reviewers are reading 10-20 applications. Your aims page needs to immediately communicate importance, innovation, and feasibility—and make them want to fund your work.
454
-
455
- ---
456
-
457
- **Key Takeaway**: The perfect Specific Aims page tells a compelling story in exactly one page—establishing a significant problem, presenting an innovative and feasible solution, showing preliminary evidence of success, and articulating transformative impact. Every sentence must earn its place.
458
-
@@ -1,156 +0,0 @@
1
- # Research Lookup Skill
2
-
3
- This skill provides real-time research information lookup using Perplexity's Sonar Pro Search model through OpenRouter.
4
-
5
- ## Setup
6
-
7
- 1. **Get OpenRouter API Key:**
8
- - Visit [openrouter.ai](https://openrouter.ai)
9
- - Create account and generate API key
10
- - Add credits to your account
11
-
12
- 2. **Configure Environment:**
13
- ```bash
14
- export OPENROUTER_API_KEY="your_api_key_here"
15
- ```
16
-
17
- 3. **Test Setup:**
18
- ```bash
19
- python scripts/research_lookup.py --model-info
20
- ```
21
-
22
- ## Usage
23
-
24
- ### Command Line Usage
25
-
26
- ```bash
27
- # Single research query
28
- python scripts/research_lookup.py "Recent advances in CRISPR gene editing 2024"
29
-
30
- # Multiple queries with delay
31
- python scripts/research_lookup.py --batch "CRISPR applications" "gene therapy trials" "ethical considerations"
32
-
33
- # Claude Code integration (called automatically)
34
- python lookup.py "your research query here"
35
- ```
36
-
37
- ### Claude Code Integration
38
-
39
- The research lookup tool is automatically available in Claude Code when you:
40
-
41
- 1. **Ask research questions:** "Research recent advances in quantum computing"
42
- 2. **Request literature reviews:** "Find current studies on climate change impacts"
43
- 3. **Need citations:** "What are the latest papers on transformer attention mechanisms?"
44
- 4. **Want technical information:** "Standard protocols for flow cytometry"
45
-
46
- ## Features
47
-
48
- - **Academic Focus:** Prioritizes peer-reviewed papers and reputable sources
49
- - **Current Information:** Focuses on recent publications (2020-2024)
50
- - **Complete Citations:** Provides full bibliographic information with DOIs
51
- - **Multiple Formats:** Supports various query types and research needs
52
- - **High Search Context:** Always uses high search context for deeper, more comprehensive research
53
- - **Quality Prioritization:** Automatically prioritizes highly-cited papers from top venues
54
- - **Cost Effective:** Typically $0.01-0.05 per research query
55
-
56
- ## Paper Quality Prioritization
57
-
58
- This skill **always prioritizes high-impact, influential papers** over obscure publications. Results are ranked by:
59
-
60
- ### Citation-Based Ranking
61
-
62
- | Paper Age | Citation Threshold | Classification |
63
- |-----------|-------------------|----------------|
64
- | 0-3 years | 20+ citations | Noteworthy |
65
- | 0-3 years | 100+ citations | Highly Influential |
66
- | 3-7 years | 100+ citations | Significant |
67
- | 3-7 years | 500+ citations | Landmark |
68
- | 7+ years | 500+ citations | Seminal |
69
- | 7+ years | 1000+ citations | Foundational |
70
-
71
- ### Venue Quality Tiers
72
-
73
- Papers from higher-tier venues are always preferred:
74
-
75
- - **Tier 1 (Highest Priority):** Nature, Science, Cell, NEJM, Lancet, JAMA, PNAS, Nature Medicine, Nature Biotechnology
76
- - **Tier 2 (High Priority):** High-impact journals (IF>10), top conferences (NeurIPS, ICML, ICLR for ML/AI)
77
- - **Tier 3 (Good):** Respected specialized journals (IF 5-10)
78
- - **Tier 4 (Use Sparingly):** Other peer-reviewed venues
79
-
80
- ### Author Reputation
81
-
82
- The skill prefers papers from:
83
- - Senior researchers with high h-index
84
- - Established research groups at recognized institutions
85
- - Authors with multiple publications in Tier-1 venues
86
- - Researchers with recognized expertise (awards, editorial positions)
87
-
88
- ### Relevance Priority
89
-
90
- 1. Papers directly addressing the research question
91
- 2. Papers with applicable methods/data
92
- 3. Tangentially related papers (only from top venues or highly cited)
93
-
94
- ## Query Examples
95
-
96
- ### Academic Research
97
- - "Recent systematic reviews on AI in medical diagnosis 2024"
98
- - "Meta-analysis of randomized controlled trials for depression treatment"
99
- - "Current state of quantum computing error correction research"
100
-
101
- ### Technical Methods
102
- - "Standard protocols for immunohistochemistry in tissue samples"
103
- - "Best practices for machine learning model validation"
104
- - "Statistical methods for analyzing longitudinal data"
105
-
106
- ### Statistical Data
107
- - "Global renewable energy adoption statistics 2024"
108
- - "Prevalence of diabetes in different populations"
109
- - "Market size for autonomous vehicles industry"
110
-
111
- ## Response Format
112
-
113
- Each research result includes:
114
- - **Summary:** Brief overview of key findings
115
- - **Key Studies:** 3-5 most relevant recent papers
116
- - **Citations:** Complete bibliographic information
117
- - **Usage Stats:** Token usage for cost tracking
118
- - **Timestamp:** When the research was performed
119
-
120
- ## Integration with Scientific Writing
121
-
122
- This skill enhances the scientific writing process by providing:
123
-
124
- 1. **Literature Reviews:** Current research for introduction sections
125
- 2. **Methods Validation:** Verify protocols against current standards
126
- 3. **Results Context:** Compare findings with recent similar studies
127
- 4. **Discussion Support:** Latest evidence for arguments
128
- 5. **Citation Management:** Properly formatted references
129
-
130
- ## Troubleshooting
131
-
132
- **"API key not found"**
133
- - Ensure `OPENROUTER_API_KEY` environment variable is set
134
- - Check that you have credits in your OpenRouter account
135
-
136
- **"Model not available"**
137
- - Verify your API key has access to Perplexity models
138
- - Check OpenRouter status page for service issues
139
-
140
- **"Rate limit exceeded"**
141
- - Add delays between requests using `--delay` option
142
- - Check your OpenRouter account limits
143
-
144
- **"No relevant results"**
145
- - Try more specific or broader queries
146
- - Include time frames (e.g., "2023-2024")
147
- - Use academic keywords and technical terms
148
-
149
- ## Cost Management
150
-
151
- - Monitor usage through OpenRouter dashboard
152
- - Typical costs: $0.01-0.05 per research query
153
- - Batch processing available for multiple queries
154
- - Consider query specificity to optimize token usage
155
-
156
- This skill is designed for academic and research purposes, providing high-quality, cited information to support scientific writing and research activities.