fleshed out aims section

ROBOT_README.md

@@ -14,6 +14,7 @@ This file serves as a robot table of contents for the repository. It lists the s
 ## Additional Directories
 
 - **agent/**: Directory containing repository files.
+- **aims_files/**: Directory containing repository files.
 - **analysis/**: Directory containing repository files.
 - **building_labagent/**: Directory containing repository files.
 - **cursor_env/**: Directory containing repository files.

aims.md

@@ -1,48 +1,207 @@
-1. Ybx1 in adipogenesis
-   1. Identifying YBX1-CEBPA-cBAF interactions in early, middle, late 3T3-L1 adipogenesis LO
-      1. Are we seeing this in all cell types?
-   2. YBX1 in adipogenic 3T3 metabolism ?
-   3. Loss of SMARCD2, SMARCE1, and YBX1 in differentating 3T3 cells CJ
-2. cBAF-CEBPa regulating mir-101 ?
-3. Ybx1 in metabolic reprogramming of hepatocytes
-   1. PPARg, CEBPa, CEBPb, SMARCD2, SMARCE1, BRG1
-   2. Posttranscriptional regulation of lipogenic genes by Ybx1
-   3. YBX1 INS1 repression
-      1. All cells except pancreatic beta cells?
-         1. Absent in pancreatic beta cells?
-            1. If so, how?
-         2. Targeting YBX1 in certain types of Type 1 diabetes mellitus
-   4. YBX1-CEBPa-cBAF in lipid-exposed hepatocytes multiomics
-      1. mRNAseq
-      2. ATACseq
-      3. ChIPseq:
-         1. YBX1,
-         2. BRG1,
-         3. CEBPa,
-         4. (and CEBPb).
-4. Using artificial intelligence to enhance biological insights
-   1. Geo stacking app ER
-   2. Transregulator-ATAC pattern finder ?
-   3. Increase read mapping speed ?
-   4. Lab agent JJ
-5. Regulation of Ybx1 cyto-nuclear translocation
-6. Metabolic regulation of gene expression
-   1. Different nutrient scenarios
-   2. Insulin, inhibit beta-oxidation, inhibit glycolysis, ATACseq
-7. Environmental affects on hepatocyte cell fate
-   1. KLFs
-   2. HepaRG
-8. Mice
-9.  Miscellaneous
-   1.  Spheroids/Organoids
-   2.  Robot
-   3.  Directional RNAseq
-   4.  DuoLink
-   5.  FA Uptake
-   6.  Proliferation
-   7.  Lipidomics
-   8.  Oxylipins
-   9.  CelSeq time series
-   10. In vitro cytonuclear proteomics
-       1.  Epigenetic memory
-           1.  Mismatch
+# Research Aims
+
+## 1. Ybx1 in adipogenesis
+### 1.1 Identifying YBX1-CEBPA-cBAF interactions in early, middle, late 3T3-L1 adipogenesis
+- **Hypothesis:** YBX1 cooperates with CEBPA and cBAF complex to regulate temporal gene expression during adipogenesis
+- **Approach:** Time-course analysis of 3T3-L1 differentiation (days 0, 2, 4, 6, 8)
+  - ChIP-seq for YBX1, CEBPA, BRG1, SMARCD2, SMARCE1
+  - RNA-seq to correlate binding with expression changes
+  - Co-IP followed by MS to identify temporal protein-protein interactions
+- **Expected outcomes:** Map dynamic transcriptional networks controlling adipocyte differentiation
+- **Question:** Are we seeing this in all cell types?
+
+### 1.2 YBX1 in adipogenic 3T3 metabolism
+- **Hypothesis:** YBX1 regulates metabolic reprogramming during adipogenesis
+- **Approach:**
+  - Metabolic profiling of control vs YBX1-depleted 3T3-L1 cells during differentiation
+  - Seahorse analysis of glycolysis and mitochondrial function
+  - Lipidomics to characterize changes in lipid composition
+  - Integration with transcriptomic data to identify YBX1-dependent metabolic pathways
+- **Expected outcomes:** Define YBX1's role in adipocyte metabolic adaptation
+
+### 1.3 Loss of SMARCD2, SMARCE1, and YBX1 in differentiating 3T3 cells
+- **Hypothesis:** cBAF subunits SMARCD2, SMARCE1 cooperate with YBX1 to maintain proper adipogenic program
+- **Approach:**
+  - CRISPR/shRNA knockdown of individual and combined factors
+  - Oil Red O staining quantification
+  - RNA-seq and ATAC-seq to identify chromatin and expression changes
+  - Rescue experiments with reconstituted factors
+- **Expected outcomes:** Mechanistic understanding of how chromatin remodeling complex and YBX1 coordinate adipogenesis
+
+## 2. cBAF-CEBPa regulating mir-101
+- **Hypothesis:** cBAF and CEBPA coordinate to regulate miR-101 expression, impacting lipid metabolism
+- **Approach:**
+  - ChIP-seq for cBAF components and CEBPA at miR-101 locus
+  - miR-101 overexpression and inhibition studies
+  - Target validation using directional RNA-seq and ribosome profiling
+  - Lipidomics to assess impact on lipid composition
+- **Expected outcomes:** Novel miRNA-mediated mechanism in metabolic control
+
+## 3. Ybx1 in metabolic reprogramming of hepatocytes
+### 3.1 Transcriptional network analysis of PPARg, CEBPa, CEBPb, SMARCD2, SMARCE1, BRG1
+- **Hypothesis:** Chronic fat exposure alters binding patterns of master regulators and chromatin remodelers
+- **Approach:**
+  - Primary hepatocytes and HepG2 cells exposed to different lipid conditions (acute vs chronic)
+  - ChIP-seq for all factors
+  - ATAC-seq to assess chromatin accessibility changes
+  - Integration with RNA-seq to identify dysregulated pathways
+- **Expected outcomes:** Map how fat exposure reshapes the regulatory landscape in hepatocytes
+
+### 3.2 Posttranscriptional regulation of lipogenic genes by Ybx1
+- **Hypothesis:** YBX1 regulates mRNA stability and translation of key lipogenic genes
+- **Approach:**
+  - RIP-seq for YBX1-bound mRNAs
+  - mRNA decay assays in control vs YBX1-depleted cells
+  - Polysome profiling coupled with RNA-seq
+  - CLIP-seq to map direct YBX1-RNA interactions
+- **Expected outcomes:** Novel posttranscriptional regulatory mechanism in lipid metabolism
+
+### 3.3 YBX1 INS1 repression
+- **Hypothesis:** YBX1 represses insulin signaling in non-pancreatic tissues
+- **Approach:**
+  - Cell-type specific analysis of YBX1 and INS1 expression
+  - Reporter assays with INS1 promoter
+  - YBX1 ChIP-seq in pancreatic vs non-pancreatic cells
+  - CRISPR activation/repression to modulate YBX1 levels
+- **Key questions:** 
+  - Is YBX1 absent in pancreatic beta cells? If so, how?
+  - Can targeting YBX1 be therapeutic for certain types of Type 1 diabetes?
+
+### 3.4 YBX1-CEBPa-cBAF in lipid-exposed hepatocytes multiomics
+- **Hypothesis:** Chronic lipid exposure alters the cooperative activity of YBX1-CEBPa-cBAF, leading to hepatic steatosis
+- **Approach:** Comprehensive multi-omic analysis integrating:
+  - mRNA-seq
+  - ATAC-seq
+  - ChIP-seq: YBX1, BRG1, CEBPa, CEBPb
+  - CelSeq2 for single-cell resolution of heterogeneous responses
+  - DUO LINK proximity assays to validate physical interactions
+  - Lipidomics to correlate with phenotypic outcomes
+- **Expected outcomes:** Systems-level understanding of transcriptional dysregulation in fatty liver development
+
+## 4. Using artificial intelligence to enhance biological insights
+### 4.1 Geo stacking app
+- **Project goal:** Develop tool to integrate and visualize multiple GEO datasets
+- **Potential applications:** Meta-analysis of metabolic disease datasets
+
+### 4.2 Transregulator-ATAC pattern finder
+- **Project goal:** Machine learning tool to predict transcription factor binding from ATAC-seq data
+- **Approach:** Train models using paired ATAC-seq and ChIP-seq datasets
+
+### 4.3 Increase read mapping speed
+- **Project goal:** Optimize computational pipeline for multi-omic data analysis
+
+### 4.4 Lab agent
+- **Project goal:** Develop AI-assisted laboratory workflow management system
+- **Applications:** Experiment planning, protocol optimization, data analysis
+
+### 4.5 ML model for oil-red O image quantification
+- **Project goal:** Automated quantification of lipid accumulation in cell culture
+- **Approach:** Computer vision models trained on labeled microscopy images
+
+## 5. Regulation of Ybx1 cyto-nuclear translocation
+- **Hypothesis:** Nutrient status regulates YBX1 localization and function
+- **Approach:**
+  - Subcellular fractionation followed by western blot
+  - Live-cell imaging with fluorescently tagged YBX1
+  - Mass spectrometry to identify post-translational modifications
+  - Mutagenesis of key regulatory sites
+- **Expected outcomes:** Understanding of how metabolic signals control YBX1 localization and function
+
+## 6. Metabolic regulation of gene expression
+- **Hypothesis:** Different nutrient environments reshape the epigenetic landscape
+- **Approach:**
+  - Treat hepatocytes with various conditions:
+    - Insulin stimulation
+    - Beta-oxidation inhibitors
+    - Glycolysis inhibitors
+  - ATAC-seq to map chromatin accessibility changes
+  - RNA-seq to identify expression changes
+  - Metabolomics to correlate with cellular metabolic state
+- **Expected outcomes:** Map how specific metabolic pathways influence gene regulation
+
+## 7. Environmental effects on hepatocyte cell fate
+- **Hypothesis:** Environmental factors reprogram hepatocytes through KLF-mediated mechanisms
+- **Approach:**
+  - HepaRG differentiation under various conditions
+  - ChIP-seq for KLF family members
+  - CelSeq2 for single-cell trajectory analysis
+  - Functional validation of key target genes
+
+## 8. Mice studies
+- **Hypothesis:** Hepatocyte-specific YBX1 deletion protects against diet-induced fatty liver
+- **Approach:**
+  - Generate hepatocyte-specific YBX1 knockout mice
+  - High-fat diet challenge
+  - Histological and biochemical analysis
+  - Multi-omic profiling of liver tissue
+
+## 9. Miscellaneous projects
+
+## 10. Spheroids/Organoids
+- **Hypothesis:** 3D culture systems better recapitulate YBX1 function in vivo
+- **Approach:**
+  - Establish liver spheroid/organoid cultures
+  - Manipulate YBX1 expression
+  - Single-cell RNA-seq for heterogeneity analysis
+  - Lipid loading experiments and imaging
+
+## 11. Robot
+- **Goal:** Automated high-throughput screening platform
+- **Applications:**
+  - Drug screening for metabolic disease
+  - Systematic CRISPR screening
+  - Automated lipid accumulation assays
+
+## 12. Directional RNAseq
+- **Hypothesis:** Antisense transcription contributes to metabolic gene regulation
+- **Approach:**
+  - Directional RNA-seq in normal vs lipid-exposed cells
+  - Integration with ChIP-seq data
+  - Functional validation of key antisense transcripts
+
+## 13. DuoLink
+- **Goal:** Map protein-protein interactions in situ
+- **Applications:**
+  - YBX1-CEBP interactions in different cellular compartments
+  - Dynamic changes in protein complexes during lipid stress
+
+## 14. FA Uptake
+- **Hypothesis:** YBX1 regulates expression of fatty acid transporters
+- **Approach:**
+  - Fluorescent fatty acid uptake assays in control vs YBX1-depleted cells
+  - ChIP-seq for YBX1 at fatty acid transporter gene loci
+  - Rescue experiments with transporter overexpression
+
+## 15. Proliferation
+- **Hypothesis:** YBX1 balances proliferation and differentiation in hepatocytes
+- **Approach:**
+  - EdU incorporation assays
+  - Cell cycle analysis in YBX1-manipulated cells
+  - Integration with RNA-seq data
+
+## 16. Lipidomics
+- **Goal:** Comprehensive profiling of lipid species changes
+- **Applications:**
+  - YBX1 knockout effects on hepatocyte lipid composition
+  - Temporal changes during fat-induced cellular reprogramming
+
+## 17. Oxylipins
+- **Hypothesis:** YBX1 regulates inflammatory signaling via oxylipin metabolism
+- **Approach:**
+  - Targeted oxylipin profiling
+  - Expression analysis of oxylipin biosynthetic enzymes
+  - Functional validation with specific inhibitors
+
+## 18. CelSeq time series
+- **Hypothesis:** Fat exposure creates heterogeneous cell populations with distinct trajectories
+- **Approach:**
+  - CelSeq2 time course during fat exposure
+  - Trajectory analysis and pseudotime ordering
+  - Identification of cell state markers
+
+## 19. In vitro cytonuclear proteomics
+- **Goal:** Map protein localization changes during metabolic stress
+- **Approach:**
+  - Subcellular fractionation followed by mass spectrometry
+  - YBX1 interactome in different cellular compartments
+  - **Specific focus:** Epigenetic memory mechanisms and chromatin mismatch repair

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+  function offsetRelativeUrl(url) {
+    const offset = getMeta("quarto:offset");
+    return offset ? offset + url : url;
+  }
+
+  function offsetAbsoluteUrl(url) {
+    const offset = getMeta("quarto:offset");
+    const baseUrl = new URL(offset, window.location);
+
+    const projRelativeUrl = url.replace(baseUrl, "");
+    if (projRelativeUrl.startsWith("/")) {
+      return projRelativeUrl;
+    } else {
+      return "/" + projRelativeUrl;
+    }
+  }
+
+  // read a meta tag value
+  function getMeta(metaName) {
+    const metas = window.document.getElementsByTagName("meta");
+    for (let i = 0; i < metas.length; i++) {
+      if (metas[i].getAttribute("name") === metaName) {
+        return metas[i].getAttribute("content");
+      }
+    }
+    return "";
+  }
+
+  async function findAndActivateCategories() {
+    // Categories search with listing only use path without query
+    const currentPagePath = offsetAbsoluteUrl(
+      window.location.origin + window.location.pathname
+    );
+    const response = await fetch(offsetRelativeUrl("listings.json"));
+    if (response.status == 200) {
+      return response.json().then(function (listingPaths) {
+        const listingHrefs = [];
+        for (const listingPath of listingPaths) {
+          const pathWithoutLeadingSlash = listingPath.listing.substring(1);
+          for (const item of listingPath.items) {
+            const encodedItem = encodeURI(item);
+            if (
+              encodedItem === currentPagePath ||
+              encodedItem === currentPagePath + "index.html"
+            ) {
+              // Resolve this path against the offset to be sure
+              // we already are using the correct path to the listing
+              // (this adjusts the listing urls to be rooted against
+              // whatever root the page is actually running against)
+              const relative = offsetRelativeUrl(pathWithoutLeadingSlash);
+              const baseUrl = window.location;
+              const resolvedPath = new URL(relative, baseUrl);
+              listingHrefs.push(resolvedPath.pathname);
+              break;
+            }
+          }
+        }
+
+        // Look up the tree for a nearby linting and use that if we find one
+        const nearestListing = findNearestParentListing(
+          offsetAbsoluteUrl(window.location.pathname),
+          listingHrefs
+        );
+        if (nearestListing) {
+          activateCategories(nearestListing);
+        } else {
+          // See if the referrer is a listing page for this item
+          const referredRelativePath = offsetAbsoluteUrl(document.referrer);
+          const referrerListing = listingHrefs.find((listingHref) => {
+            const isListingReferrer =
+              listingHref === referredRelativePath ||
+              listingHref === referredRelativePath + "index.html";
+            return isListingReferrer;
+          });
+
+          if (referrerListing) {
+            // Try to use the referrer if possible
+            activateCategories(referrerListing);
+          } else if (listingHrefs.length > 0) {
+            // Otherwise, just fall back to the first listing
+            activateCategories(listingHrefs[0]);
+          }
+        }
+      });
+    }
+  }
+  if (hasTitleCategories()) {
+    findAndActivateCategories();
+  }
+
+  const findNearestParentListing = (href, listingHrefs) => {
+    if (!href || !listingHrefs) {
+      return undefined;
+    }
+    // Look up the tree for a nearby linting and use that if we find one
+    const relativeParts = href.substring(1).split("/");
+    while (relativeParts.length > 0) {
+      const path = relativeParts.join("/");
+      for (const listingHref of listingHrefs) {
+        if (listingHref.startsWith(path)) {
+          return listingHref;
+        }
+      }
+      relativeParts.pop();
+    }
+
+    return undefined;
+  };
+
+  const manageSidebarVisiblity = (el, placeholderDescriptor) => {
+    let isVisible = true;
+    let elRect;
+
+    return (hiddenRegions) => {
+      if (el === null) {
+        return;
+      }
+
+      // Find the last element of the TOC
+      const lastChildEl = el.lastElementChild;
+
+      if (lastChildEl) {
+        // Converts the sidebar to a menu
+        const convertToMenu = () => {
+          for (const child of el.children) {
+            child.style.opacity = 0;
+            child.style.overflow = "hidden";
+            child.style.pointerEvents = "none";
+          }
+
+          nexttick(() => {
+            const toggleContainer = window.document.createElement("div");
+            toggleContainer.style.width = "100%";
+            toggleContainer.classList.add("zindex-over-content");
+            toggleContainer.classList.add("quarto-sidebar-toggle");
+            toggleContainer.classList.add("headroom-target"); // Marks this to be managed by headeroom
+            toggleContainer.id = placeholderDescriptor.id;
+            toggleContainer.style.position = "fixed";
+
+            const toggleIcon = window.document.createElement("i");
+            toggleIcon.classList.add("quarto-sidebar-toggle-icon");
+            toggleIcon.classList.add("bi");
+            toggleIcon.classList.add("bi-caret-down-fill");
+
+            const toggleTitle = window.document.createElement("div");
+            const titleEl = window.document.body.querySelector(
+              placeholderDescriptor.titleSelector
+            );
+            if (titleEl) {
+              toggleTitle.append(
+                titleEl.textContent || titleEl.innerText,
+                toggleIcon
+              );
+            }
+            toggleTitle.classList.add("zindex-over-content");
+            toggleTitle.classList.add("quarto-sidebar-toggle-title");
+            toggleContainer.append(toggleTitle);
+
+            const toggleContents = window.document.createElement("div");
+            toggleContents.classList = el.classList;
+            toggleContents.classList.add("zindex-over-content");
+            toggleContents.classList.add("quarto-sidebar-toggle-contents");
+            for (const child of el.children) {
+              if (child.id === "toc-title") {
+                continue;
+              }
+
+              const clone = child.cloneNode(true);
+              clone.style.opacity = 1;
+              clone.style.pointerEvents = null;
+              clone.style.display = null;
+              toggleContents.append(clone);
+            }
+            toggleContents.style.height = "0px";
+            const positionToggle = () => {
+              // position the element (top left of parent, same width as parent)
+              if (!elRect) {
+                elRect = el.getBoundingClientRect();
+              }
+              toggleContainer.style.left = `${elRect.left}px`;
+              toggleContainer.style.top = `${elRect.top}px`;
+              toggleContainer.style.width = `${elRect.width}px`;
+            };
+            positionToggle();
+
+            toggleContainer.append(toggleContents);
+            el.parentElement.prepend(toggleContainer);
+
+            // Process clicks
+            let tocShowing = false;
+            // Allow the caller to control whether this is dismissed
+            // when it is clicked (e.g. sidebar navigation supports
+            // opening and closing the nav tree, so don't dismiss on click)
+            const clickEl = placeholderDescriptor.dismissOnClick
+              ? toggleContainer
+              : toggleTitle;
+
+            const closeToggle = () => {
+              if (tocShowing) {
+                toggleContainer.classList.remove("expanded");
+                toggleContents.style.height = "0px";
+                tocShowing = false;
+              }
+            };
+
+            // Get rid of any expanded toggle if the user scrolls
+            window.document.addEventListener(
+              "scroll",
+              throttle(() => {
+                closeToggle();
+              }, 50)
+            );
+
+            // Handle positioning of the toggle
+            window.addEventListener(
+              "resize",
+              throttle(() => {
+                elRect = undefined;
+                positionToggle();
+              }, 50)
+            );
+
+            window.addEventListener("quarto-hrChanged", () => {
+              elRect = undefined;
+            });
+
+            // Process the click
+            clickEl.onclick = () => {
+              if (!tocShowing) {
+                toggleContainer.classList.add("expanded");
+                toggleContents.style.height = null;
+                tocShowing = true;
+              } else {
+                closeToggle();
+              }
+            };
+          });
+        };
+
+        // Converts a sidebar from a menu back to a sidebar
+        const convertToSidebar = () => {
+          for (const child of el.children) {
+            child.style.opacity = 1;
+            child.style.overflow = null;
+            child.style.pointerEvents = null;
+          }
+
+          const placeholderEl = window.document.getElementById(
+            placeholderDescriptor.id
+          );
+          if (placeholderEl) {
+            placeholderEl.remove();
+          }
+
+          el.classList.remove("rollup");
+        };
+
+        if (isReaderMode()) {
+          convertToMenu();
+          isVisible = false;
+        } else {
+          // Find the top and bottom o the element that is being managed
+          const elTop = el.offsetTop;
+          const elBottom =
+            elTop + lastChildEl.offsetTop + lastChildEl.offsetHeight;
+
+          if (!isVisible) {
+            // If the element is current not visible reveal if there are
+            // no conflicts with overlay regions
+            if (!inHiddenRegion(elTop, elBottom, hiddenRegions)) {
+              convertToSidebar();
+              isVisible = true;
+            }
+          } else {
+            // If the element is visible, hide it if it conflicts with overlay regions
+            // and insert a placeholder toggle (or if we're in reader mode)
+            if (inHiddenRegion(elTop, elBottom, hiddenRegions)) {
+              convertToMenu();
+              isVisible = false;
+            }
+          }
+        }
+      }
+    };
+  };
+
+  const tabEls = document.querySelectorAll('a[data-bs-toggle="tab"]');
+  for (const tabEl of tabEls) {
+    const id = tabEl.getAttribute("data-bs-target");
+    if (id) {
+      const columnEl = document.querySelector(
+        `${id} .column-margin, .tabset-margin-content`
+      );
+      if (columnEl)
+        tabEl.addEventListener("shown.bs.tab", function (event) {
+          const el = event.srcElement;
+          if (el) {
+            const visibleCls = `${el.id}-margin-content`;
+            // walk up until we find a parent tabset
+            let panelTabsetEl = el.parentElement;
+            while (panelTabsetEl) {
+              if (panelTabsetEl.classList.contains("panel-tabset")) {
+                break;
+              }
+              panelTabsetEl = panelTabsetEl.parentElement;
+            }
+
+            if (panelTabsetEl) {
+              const prevSib = panelTabsetEl.previousElementSibling;
+              if (
+                prevSib &&
+                prevSib.classList.contains("tabset-margin-container")
+              ) {
+                const childNodes = prevSib.querySelectorAll(
+                  ".tabset-margin-content"
+                );
+                for (const childEl of childNodes) {
+                  if (childEl.classList.contains(visibleCls)) {
+                    childEl.classList.remove("collapse");
+                  } else {
+                    childEl.classList.add("collapse");
+                  }
+                }
+              }
+            }
+          }
+
+          layoutMarginEls();
+        });
+    }
+  }
+
+  // Manage the visibility of the toc and the sidebar
+  const marginScrollVisibility = manageSidebarVisiblity(marginSidebarEl, {
+    id: "quarto-toc-toggle",
+    titleSelector: "#toc-title",
+    dismissOnClick: true,
+  });
+  const sidebarScrollVisiblity = manageSidebarVisiblity(sidebarEl, {
+    id: "quarto-sidebarnav-toggle",
+    titleSelector: ".title",
+    dismissOnClick: false,
+  });
+  let tocLeftScrollVisibility;
+  if (leftTocEl) {
+    tocLeftScrollVisibility = manageSidebarVisiblity(leftTocEl, {
+      id: "quarto-lefttoc-toggle",
+      titleSelector: "#toc-title",
+      dismissOnClick: true,
+    });
+  }
+
+  // Find the first element that uses formatting in special columns
+  const conflictingEls = window.document.body.querySelectorAll(
+    '[class^="column-"], [class*=" column-"], aside, [class*="margin-caption"], [class*=" margin-caption"], [class*="margin-ref"], [class*=" margin-ref"]'
+  );
+
+  // Filter all the possibly conflicting elements into ones
+  // the do conflict on the left or ride side
+  const arrConflictingEls = Array.from(conflictingEls);
+  const leftSideConflictEls = arrConflictingEls.filter((el) => {
+    if (el.tagName === "ASIDE") {
+      return false;
+    }
+    return Array.from(el.classList).find((className) => {
+      return (
+        className !== "column-body" &&
+        className.startsWith("column-") &&
+        !className.endsWith("right") &&
+        !className.endsWith("container") &&
+        className !== "column-margin"
+      );
+    });
+  });
+  const rightSideConflictEls = arrConflictingEls.filter((el) => {
+    if (el.tagName === "ASIDE") {
+      return true;
+    }
+
+    const hasMarginCaption = Array.from(el.classList).find((className) => {
+      return className == "margin-caption";
+    });
+    if (hasMarginCaption) {
+      return true;
+    }
+
+    return Array.from(el.classList).find((className) => {
+      return (
+        className !== "column-body" &&
+        !className.endsWith("container") &&
+        className.startsWith("column-") &&
+        !className.endsWith("left")
+      );
+    });
+  });
+
+  const kOverlapPaddingSize = 10;
+  function toRegions(els) {
+    return els.map((el) => {
+      const boundRect = el.getBoundingClientRect();
+      const top =
+        boundRect.top +
+        document.documentElement.scrollTop -
+        kOverlapPaddingSize;
+      return {
+        top,
+        bottom: top + el.scrollHeight + 2 * kOverlapPaddingSize,
+      };
+    });
+  }
+
+  let hasObserved = false;
+  const visibleItemObserver = (els) => {
+    let visibleElements = [...els];
+    const intersectionObserver = new IntersectionObserver(
+      (entries, _observer) => {
+        entries.forEach((entry) => {
+          if (entry.isIntersecting) {
+            if (visibleElements.indexOf(entry.target) === -1) {
+              visibleElements.push(entry.target);
+            }
+          } else {
+            visibleElements = visibleElements.filter((visibleEntry) => {
+              return visibleEntry !== entry;
+            });
+          }
+        });
+
+        if (!hasObserved) {
+          hideOverlappedSidebars();
+        }
+        hasObserved = true;
+      },
+      {}
+    );
+    els.forEach((el) => {
+      intersectionObserver.observe(el);
+    });
+
+    return {
+      getVisibleEntries: () => {
+        return visibleElements;
+      },
+    };
+  };
+
+  const rightElementObserver = visibleItemObserver(rightSideConflictEls);
+  const leftElementObserver = visibleItemObserver(leftSideConflictEls);
+
+  const hideOverlappedSidebars = () => {
+    marginScrollVisibility(toRegions(rightElementObserver.getVisibleEntries()));
+    sidebarScrollVisiblity(toRegions(leftElementObserver.getVisibleEntries()));
+    if (tocLeftScrollVisibility) {
+      tocLeftScrollVisibility(
+        toRegions(leftElementObserver.getVisibleEntries())
+      );
+    }
+  };
+
+  window.quartoToggleReader = () => {
+    // Applies a slow class (or removes it)
+    // to update the transition speed
+    const slowTransition = (slow) => {
+      const manageTransition = (id, slow) => {
+        const el = document.getElementById(id);
+        if (el) {
+          if (slow) {
+            el.classList.add("slow");
+          } else {
+            el.classList.remove("slow");
+          }
+        }
+      };
+
+      manageTransition("TOC", slow);
+      manageTransition("quarto-sidebar", slow);
+    };
+    const readerMode = !isReaderMode();
+    setReaderModeValue(readerMode);
+
+    // If we're entering reader mode, slow the transition
+    if (readerMode) {
+      slowTransition(readerMode);
+    }
+    highlightReaderToggle(readerMode);
+    hideOverlappedSidebars();
+
+    // If we're exiting reader mode, restore the non-slow transition
+    if (!readerMode) {
+      slowTransition(!readerMode);
+    }
+  };
+
+  const highlightReaderToggle = (readerMode) => {
+    const els = document.querySelectorAll(".quarto-reader-toggle");
+    if (els) {
+      els.forEach((el) => {
+        if (readerMode) {
+          el.classList.add("reader");
+        } else {
+          el.classList.remove("reader");
+        }
+      });
+    }
+  };
+
+  const setReaderModeValue = (val) => {
+    if (window.location.protocol !== "file:") {
+      window.localStorage.setItem("quarto-reader-mode", val);
+    } else {
+      localReaderMode = val;
+    }
+  };
+
+  const isReaderMode = () => {
+    if (window.location.protocol !== "file:") {
+      return window.localStorage.getItem("quarto-reader-mode") === "true";
+    } else {
+      return localReaderMode;
+    }
+  };
+  let localReaderMode = null;
+
+  const tocOpenDepthStr = tocEl?.getAttribute("data-toc-expanded");
+  const tocOpenDepth = tocOpenDepthStr ? Number(tocOpenDepthStr) : 1;
+
+  // Walk the TOC and collapse/expand nodes
+  // Nodes are expanded if:
+  // - they are top level
+  // - they have children that are 'active' links
+  // - they are directly below an link that is 'active'
+  const walk = (el, depth) => {
+    // Tick depth when we enter a UL
+    if (el.tagName === "UL") {
+      depth = depth + 1;
+    }
+
+    // It this is active link
+    let isActiveNode = false;
+    if (el.tagName === "A" && el.classList.contains("active")) {
+      isActiveNode = true;
+    }
+
+    // See if there is an active child to this element
+    let hasActiveChild = false;
+    for (const child of el.children) {
+      hasActiveChild = walk(child, depth) || hasActiveChild;
+    }
+
+    // Process the collapse state if this is an UL
+    if (el.tagName === "UL") {
+      if (tocOpenDepth === -1 && depth > 1) {
+        // toc-expand: false
+        el.classList.add("collapse");
+      } else if (
+        depth <= tocOpenDepth ||
+        hasActiveChild ||
+        prevSiblingIsActiveLink(el)
+      ) {
+        el.classList.remove("collapse");
+      } else {
+        el.classList.add("collapse");
+      }
+
+      // untick depth when we leave a UL
+      depth = depth - 1;
+    }
+    return hasActiveChild || isActiveNode;
+  };
+
+  // walk the TOC and expand / collapse any items that should be shown
+  if (tocEl) {
+    updateActiveLink();
+    walk(tocEl, 0);
+  }
+
+  // Throttle the scroll event and walk peridiocally
+  window.document.addEventListener(
+    "scroll",
+    throttle(() => {
+      if (tocEl) {
+        updateActiveLink();
+        walk(tocEl, 0);
+      }
+      if (!isReaderMode()) {
+        hideOverlappedSidebars();
+      }
+    }, 5)
+  );
+  window.addEventListener(
+    "resize",
+    throttle(() => {
+      if (tocEl) {
+        updateActiveLink();
+        walk(tocEl, 0);
+      }
+      if (!isReaderMode()) {
+        hideOverlappedSidebars();
+      }
+    }, 10)
+  );
+  hideOverlappedSidebars();
+  highlightReaderToggle(isReaderMode());
+});
+
+tabsets.init();
+
+function throttle(func, wait) {
+  let waiting = false;
+  return function () {
+    if (!waiting) {
+      func.apply(this, arguments);
+      waiting = true;
+      setTimeout(function () {
+        waiting = false;
+      }, wait);
+    }
+  };
+}
+
+function nexttick(func) {
+  return setTimeout(func, 0);
+}

aims_files/libs/quarto-html/tabsets/tabsets.js

@@ -0,0 +1,95 @@
+// grouped tabsets
+
+export function init() {
+  window.addEventListener("pageshow", (_event) => {
+    function getTabSettings() {
+      const data = localStorage.getItem("quarto-persistent-tabsets-data");
+      if (!data) {
+        localStorage.setItem("quarto-persistent-tabsets-data", "{}");
+        return {};
+      }
+      if (data) {
+        return JSON.parse(data);
+      }
+    }
+
+    function setTabSettings(data) {
+      localStorage.setItem(
+        "quarto-persistent-tabsets-data",
+        JSON.stringify(data)
+      );
+    }
+
+    function setTabState(groupName, groupValue) {
+      const data = getTabSettings();
+      data[groupName] = groupValue;
+      setTabSettings(data);
+    }
+
+    function toggleTab(tab, active) {
+      const tabPanelId = tab.getAttribute("aria-controls");
+      const tabPanel = document.getElementById(tabPanelId);
+      if (active) {
+        tab.classList.add("active");
+        tabPanel.classList.add("active");
+      } else {
+        tab.classList.remove("active");
+        tabPanel.classList.remove("active");
+      }
+    }
+
+    function toggleAll(selectedGroup, selectorsToSync) {
+      for (const [thisGroup, tabs] of Object.entries(selectorsToSync)) {
+        const active = selectedGroup === thisGroup;
+        for (const tab of tabs) {
+          toggleTab(tab, active);
+        }
+      }
+    }
+
+    function findSelectorsToSyncByLanguage() {
+      const result = {};
+      const tabs = Array.from(
+        document.querySelectorAll(`div[data-group] a[id^='tabset-']`)
+      );
+      for (const item of tabs) {
+        const div = item.parentElement.parentElement.parentElement;
+        const group = div.getAttribute("data-group");
+        if (!result[group]) {
+          result[group] = {};
+        }
+        const selectorsToSync = result[group];
+        const value = item.innerHTML;
+        if (!selectorsToSync[value]) {
+          selectorsToSync[value] = [];
+        }
+        selectorsToSync[value].push(item);
+      }
+      return result;
+    }
+
+    function setupSelectorSync() {
+      const selectorsToSync = findSelectorsToSyncByLanguage();
+      Object.entries(selectorsToSync).forEach(([group, tabSetsByValue]) => {
+        Object.entries(tabSetsByValue).forEach(([value, items]) => {
+          items.forEach((item) => {
+            item.addEventListener("click", (_event) => {
+              setTabState(group, value);
+              toggleAll(value, selectorsToSync[group]);
+            });
+          });
+        });
+      });
+      return selectorsToSync;
+    }
+
+    const selectorsToSync = setupSelectorSync();
+    for (const [group, selectedName] of Object.entries(getTabSettings())) {
+      const selectors = selectorsToSync[group];
+      // it's possible that stale state gives us empty selections, so we explicitly check here.
+      if (selectors) {
+        toggleAll(selectedName, selectors);
+      }
+    }
+  });
+}

aims_files/libs/quarto-html/tippy.css

@@ -0,0 +1 @@
+.tippy-box[data-animation=fade][data-state=hidden]{opacity:0}[data-tippy-root]{max-width:calc(100vw - 10px)}.tippy-box{position:relative;background-color:#333;color:#fff;border-radius:4px;font-size:14px;line-height:1.4;white-space:normal;outline:0;transition-property:transform,visibility,opacity}.tippy-box[data-placement^=top]>.tippy-arrow{bottom:0}.tippy-box[data-placement^=top]>.tippy-arrow:before{bottom:-7px;left:0;border-width:8px 8px 0;border-top-color:initial;transform-origin:center top}.tippy-box[data-placement^=bottom]>.tippy-arrow{top:0}.tippy-box[data-placement^=bottom]>.tippy-arrow:before{top:-7px;left:0;border-width:0 8px 8px;border-bottom-color:initial;transform-origin:center bottom}.tippy-box[data-placement^=left]>.tippy-arrow{right:0}.tippy-box[data-placement^=left]>.tippy-arrow:before{border-width:8px 0 8px 8px;border-left-color:initial;right:-7px;transform-origin:center left}.tippy-box[data-placement^=right]>.tippy-arrow{left:0}.tippy-box[data-placement^=right]>.tippy-arrow:before{left:-7px;border-width:8px 8px 8px 0;border-right-color:initial;transform-origin:center right}.tippy-box[data-inertia][data-state=visible]{transition-timing-function:cubic-bezier(.54,1.5,.38,1.11)}.tippy-arrow{width:16px;height:16px;color:#333}.tippy-arrow:before{content:"";position:absolute;border-color:transparent;border-style:solid}.tippy-content{position:relative;padding:5px 9px;z-index:1}