From 368ff961baffe81dcba20e0b77509fc908ee5240 Mon Sep 17 00:00:00 2001 From: LLLin000 <809867916@qq.com> Date: Fri, 3 Jul 2026 17:45:56 +0800 Subject: [PATCH] feat(ocr): switch figure inventory wrapper to vnext by default --- .../worker/ocr_figure_vnext_sidecar_pass.py | 10 +- paperforge/worker/ocr_figures.py | 2 +- .../2026-07-03-vnext-cutover-corpus-map.md | 123 ++++++++++++ .../24YKLTHQ/blocks.structured.jsonl | 182 ++++++++++++++++++ .../28JLIHLS/blocks.structured.jsonl | 161 ++++++++++++++++ tests/test_ocr_figure_vnext_real_papers.py | 22 +++ 6 files changed, 495 insertions(+), 5 deletions(-) create mode 100644 project/current/2026-07-03-vnext-cutover-corpus-map.md create mode 100644 tests/fixtures/ocr_vnext_real_papers/24YKLTHQ/blocks.structured.jsonl create mode 100644 tests/fixtures/ocr_vnext_real_papers/28JLIHLS/blocks.structured.jsonl diff --git a/paperforge/worker/ocr_figure_vnext_sidecar_pass.py b/paperforge/worker/ocr_figure_vnext_sidecar_pass.py index 0b8abaef..e47cb365 100644 --- a/paperforge/worker/ocr_figure_vnext_sidecar_pass.py +++ b/paperforge/worker/ocr_figure_vnext_sidecar_pass.py @@ -52,10 +52,12 @@ class SidecarPass: # Skip captions already protected by an earlier pass protected = False for match in state.matches: - if str(match.get("legend_block_id", "")) == cid: - if ocr_figures._has_protected_figure_ownership(match): - protected = True - break + if ( + str(match.get("legend_block_id", "")) == cid + and ocr_figures._has_protected_figure_ownership(match) + ): + protected = True + break if protected: continue diff --git a/paperforge/worker/ocr_figures.py b/paperforge/worker/ocr_figures.py index 891552fd..7f21ade0 100644 --- a/paperforge/worker/ocr_figures.py +++ b/paperforge/worker/ocr_figures.py @@ -2979,7 +2979,7 @@ def _infer_missing_main_figure_numbers( def build_figure_inventory(structured_blocks: list[dict], page_width: float = 1200, page_pdf_lines_by_page: dict[int, list[dict]] | None = None) -> dict[str, Any]: - return build_figure_inventory_legacy(structured_blocks, page_width, page_pdf_lines_by_page) + return build_figure_inventory_vnext(structured_blocks, page_width) def build_figure_inventory_vnext(structured_blocks: list[dict], page_width: float = 1200) -> dict[str, Any]: from .ocr_figure_vnext_accounting_pass import FinalAccountingPass diff --git a/project/current/2026-07-03-vnext-cutover-corpus-map.md b/project/current/2026-07-03-vnext-cutover-corpus-map.md new file mode 100644 index 00000000..e4393085 --- /dev/null +++ b/project/current/2026-07-03-vnext-cutover-corpus-map.md @@ -0,0 +1,123 @@ +# VNext Cutover Corpus Map + +**Date:** 2026-07-03 +**Purpose:** Map the comparison corpus for OCR vnext cutover evaluation (spec §8.3). +**Total papers:** 5 (3 existing fixtures + 2 new) + +## Coverage Summary + +| Category | Paper(s) | Coverage | +|----------|----------|----------| +| same-page normal figure | 2HEUD5P9 | Strong | +| multi-panel same-row group | 2HEUD5P9 | Strong | +| sidecar legend page | 28JLIHLS | Strong | +| bundle-source page | DWQQK2YB | Moderate | +| locator-bridge page | DWQQK2YB | Moderate | +| dense composite parent page | 24YKLTHQ | Strong | +| classic sequential-only rescue page | YGH7VEX6 | Strong | +| unmatched asset / unresolved cluster page | 2HEUD5P9 | Strong | +| duplicated / continued legend page | DWQQK2YB | Moderate | + +**Missing categories:** None — all 9 spec §8.3 categories are covered. + +--- + +## Existing Fixtures (3 papers) + +### 2HEUD5P9 — Same-page, multi-panel, unmatched assets + +**Blocks:** 670 | **Pages:** 27 | **Source:** Vault (existing fixture) + +**Categories covered:** +- **same-page normal figure** — Pages 3, 4, 9, 13, 15, 19, 21 all have `figure_caption` blocks with `figure_asset` blocks on the same page. PrimarySamePagePass is exercised on each. +- **multi-panel same-row group** — Page 4: 1 caption ("Figure 2") with 14 figure assets. Page 9: 1 caption ("Figure 3") with 15 figure assets. These are multi-panel figures where multiple asset blocks share one caption. The pipeline's distance clustering forms candidate groups that the same-page pass matches. +- **unmatched asset / unresolved cluster page** — 74 figure assets total vs 8 figure captions. Pages 21, 15, 13, and others have assets that greatly outnumber captions. After all matching passes, the residual assets remain as unresolved clusters for FinalAccountingPass and UnresolvedClusterConsolidation. + +**Why chosen:** Largest existing fixture with richest figure layout — covers 3 spec categories. + +--- + +### DWQQK2YB — Cross-page, locator bridge, bundle source, duplicated legend + +**Blocks:** 273 | **Pages:** 41 | **Source:** Vault (existing fixture) + +**Categories covered:** +- **cross-page layout** — Captions on pages 35-36 point to assets on pages 37-41. CrossPageReservationPass and CrossPageSettlementPass must bridge the gap. +- **locator-bridge page** — Caption text spans across the page boundary; the locator bridge pass connects figure captions on early pages to their visual groups on later pages. Pages 35-36 have caption candidates while corresponding assets appear on pages 37-41. +- **bundle-source page** — Page 35: 3 `figure_caption_candidate` blocks (Fig. 1-3) with 0 `figure_asset` blocks. This triggers the LegendBundlePass, which must match these 3 bundled captions to assets on subsequent pages. +- **duplicated / continued legend page** — Fig. 3 appears on both page 35 (as candidate) and page 40 (as candidate text). Fig. 4 appears on page 36 and page 41. This exercises the deduplication logic and tests that duplicated captions don't create spurious matches. + +**Why chosen:** Only fixture exercising locator bridge, bundle source, and duplicated legend — coverage breadth. + +--- + +### YGH7VEX6 — Classic sequential rescue + +**Blocks:** 189 | **Pages:** 8 | **Source:** Vault (existing fixture) + +**Categories covered:** +- **classic sequential-only rescue page** — 14 figure captions, but only 12 expected to match via same-page passes (per brief). The residual 2 unmatched captions fall through to ClassicSequentialPass, which matches them to forward-page assets in reading order. This exercises the fallback matching path. + +**Why chosen:** Small (189 blocks, 8 pages) with dense caption-asset arrangement. The 2-gap pattern is the most compact regression test for classic sequential matching. + +--- + +## New Fixtures (2 papers) + +### 28JLIHLS — Sidecar legend page + +**Blocks:** 161 | **Pages:** 7 | **Source:** Vault (new fixture) + +**Categories covered:** +- **sidecar legend page** — Pages 3-4 each have 3 `figure_caption` blocks with widths ~488-491px (narrow on a 1200px page width) and 2-3 matching `figure_asset` blocks. The narrow caption width (< 600px) causes low same-page matching scores, making these captions candidates for the SidecarPass. The pass must match each narrow caption to its nearest asset band by y-alignment. + +**Paper details:** +- Full title: "Galvanotaxis of chondrocytes" +- 7 figure captions total (Fig. 1-7), 6 figure assets +- Fig. 1 on page 2 (full width) — standard same-page match +- Fig. 2-4 on page 3 (narrow) — sidecar candidates +- Fig. 5-7 on page 4 (narrow) — sidecar candidates +- Remaining pages (5-7): references, footnotes, noise + +**Why chosen:** Very small (161 blocks) with the cleanest sidecar pattern in the vault — multiple adjacent pages each with 3 narrow captions and matching assets. + +--- + +### 24YKLTHQ — Dense composite parent page + +**Blocks:** 182 | **Pages:** 13 | **Source:** Vault (new fixture) + +**Categories covered:** +- **dense composite parent page** — Page 7: 1 `figure_caption` block ("Figure 5: Distribution of EFs in cartilage explant cultured in vitro") with 8 `figure_asset` blocks, 0 `body_paragraph` blocks. This dense arrangement of assets with a single caption exercises CompositeParentPass, which must detect the composite parent cluster and match it to the single caption. + +**Paper details:** +- Full title: "Computational modelling of electric field distribution in cartilage" +- 9 figure captions, 16 figure assets +- Pages 3, 5, 6, 7, 8: caption+asset pages +- Page 7 is the primary dense composite target (8 assets clustered, 1 caption) +- Additional pages (4): 2 narrow "Source: own" caption candidates (sidecar-adjacent pattern, secondary) +- Remaining pages: references, noise, metadata + +**Why chosen:** Small (182 blocks) with the clearest dense composite page in the vault — high asset density and zero body interference on page 7. + +--- + +## Source Paths + +All fixtures are copies of `blocks.structured.jsonl` from the OCR vault: + +| Key | Vault Path | +|-----|-----------| +| 2HEUD5P9 | `D:/L/OB/Literature-hub/System/PaperForge/ocr/2HEUD5P9/structure/blocks.structured.jsonl` | +| DWQQK2YB | `D:/L/OB/Literature-hub/System/PaperForge/ocr/DWQQK2YB/structure/blocks.structured.jsonl` | +| YGH7VEX6 | `D:/L/OB/Literature-hub/System/PaperForge/ocr/YGH7VEX6/structure/blocks.structured.jsonl` | +| 28JLIHLS | `D:/L/OB/Literature-hub/System/PaperForge/ocr/28JLIHLS/structure/blocks.structured.jsonl` | +| 24YKLTHQ | `D:/L/OB/Literature-hub/System/PaperForge/ocr/24YKLTHQ/structure/blocks.structured.jsonl` | + +## Notes + +- One paper covers multiple categories where the layout naturally demonstrates more than one pattern (e.g., DWQQK2YB covers 4 categories). +- All 9 required categories from spec §8.3 are covered by at least one paper. +- Each category has at least "Moderate" coverage (verifiable from block role/page analysis). +- New fixtures were selected for small size (<200 blocks) and clear category signal. +- No text-matching was used in fixture selection — only structural signals (bbox width, role distribution, asset-to-caption ratio, page composition). diff --git 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17, "raw_label": "abstract", "raw_order": 11, "bbox": [439, 536, 1117, 916], "text": "Electrical stimulation is a non-invasive therapy used to stimulate chondrocyte dynamics: proliferation, migration, morphology and molecular synthesis. Some studies have evidenced the role of frequency in the generation of electric fields; however, the electrical stimulation sensed by chondrocytes when the frequency varies is not well-documented. Accordingly, a computational model was implemented to assess the frequency dependence of electric fields that stimulate chondrocytes. Cells were modelled in three different scenarios: monolayer cultures, cartilage explants and scaffolds. Chondrocytes were stimulated with 100 Vp-p at frequencies of 0.001, 1, 10, 50, 100 and 1000 kHz. Results showed that frequency is a relevant factor when considering the stimulation of biological samples, since electric fields increased as frequencies were higher. Moreover, chondrocytes experienced different electric fields in both cytoplasm and extracellular environment. This model provides relevant information about the electrical parameters to stimulate cells; in fact, it could enhance experimental procedures, predicting the stimulation that improves chondrocyte dynamics. Electric fields are a promising tool to maintain either well-structured chondrocytes or biomimetic materials used in regenerative therapies such as autologous implantation to treat hyaline cartilage injuries.", "page_width": 1225, "page_height": 1582, "role": "abstract_body", "role_confidence": 0.85, "evidence": ["abstract label from Paddle OCR"], "seed_role": "abstract_body", "seed_confidence": 0.85, "seed_evidence": ["abstract label from Paddle OCR"], "span_metadata": [{"size": 7.970099925994873, "font": "CMR8", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 7.970099925994873, "font": "CMR8", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 7.970099925994873, "font": "CMR8", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 7.970099925994873, "font": "CMR8", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 7.970099925994873, "font": "CMR8", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 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non-invasive therapy used to stimulate chondrocyte dynamics: proliferation, migration, morphology and molecular synthesis. Some studies have evidenced the role of frequency in the generation of electric fields; however, the electrical stimulation sensed by chondrocytes when the frequency varies is not well-documented. Accordingly, a computational model was implemented to assess the frequency dependence of electric fields that stimulate chondrocytes. Cells were modelled in three different scenarios: monolayer cultures, cartilage explants and scaffolds. Chondrocytes were stimulated with 100 Vp-p at frequencies of 0.001, 1, 10, 50, 100 and 1000 kHz. Results showed that frequency is a relevant factor when considering the stimulation of biological samples, since electric fields increased as frequencies were higher. Moreover, chondrocytes experienced different electric fields in both cytoplasm and extracellular environment. This model provides relevant information about the electrical parameters to stimulate cells; in fact, it could enhance experimental procedures, predicting the stimulation that improves chondrocyte dynamics. Electric fields are a promising tool to maintain either well-structured chondrocytes or biomimetic materials used in regenerative therapies such as autologous implantation to treat hyaline cartilage injuries.", "bbox": [439, 536, 1117, 916], "page_width": 1225, "page_height": 1582}, "marker_signature": {"type": "none", "raw_marker": null, "number": null, "kind": "generic_text", "normalized_text": "Electrical stimulation is a non-invasive therapy used to stimulate chondrocyte dynamics: proliferation, migration, morphology and molecular synthesis. Some studies have evidenced the role of frequency in the generation of electric fields; however, the electrical stimulation sensed by chondrocytes when the frequency varies is not well-documented. Accordingly, a computational model was implemented to assess the frequency dependence of electric fields that stimulate chondrocytes. Cells were modelled in three different scenarios: monolayer cultures, cartilage explants and scaffolds. Chondrocytes were stimulated with 100 Vp-p at frequencies of 0.001, 1, 10, 50, 100 and 1000 kHz. Results showed that frequency is a relevant factor when considering the stimulation of biological samples, since electric fields increased as frequencies were higher. Moreover, chondrocytes experienced different electric fields in both cytoplasm and extracellular environment. This model provides relevant information about the electrical parameters to stimulate cells; in fact, it could enhance experimental procedures, predicting the stimulation that improves chondrocyte dynamics. Electric fields are a promising tool to maintain either well-structured chondrocytes or biomimetic materials used in regenerative therapies such as autologous implantation to treat hyaline cartilage injuries."}, "layout_signature": {"width": 678, "width_bucket": 675, "height": 380, "left": 439, "top": 536, "right": 1117, "bottom": 916, "x_center": 778.0, "x_center_bucket": 775, "y_center": 726.0, "x_ratio": 0.6351, "y_ratio": 0.4589, "width_ratio": 0.5535, "height_ratio": 0.2402, "line_count": 1}, "span_signature": {"font_size": 7.97, "font_size_median": 7.97, "font_size_bucket": 8.0, "font_family_norm": "CMR8", "bold": false, "italic": true, "span_count": 304}, "_in_visual_container": null, "_container_bbox": null, "_container_text": null, "_text_source": null, "_ocr_raw_status": null, "_ocr_raw_error_type": null, "render_default": true, "index_default": true, "zone": "frontmatter_main_zone", "style_family": "support_like", "style_family_authority": "zone_context", "reading_band_id": "band_062", "display_cluster_candidate_id": "", "layout_region": "reference_candidate", "boundary_before": "weak", "boundary_after": "none", "bridge_eligible": false, "insert_score": {"score": 0.0, "decision": "body", "evidence": []}, "role_verification_status": "ACCEPT", "role_source": "abstract_span_body", "role_evidence": ["abstract body matched span"]} +{"paper_id": "24YKLTHQ", "page": 1, "block_id": 18, "raw_label": "paragraph_title", "raw_order": 12, "bbox": [442, 924, 534, 944], "text": "RESUMEN", "page_width": 1225, "page_height": 1582, "role": "section_heading", "role_confidence": 0.5, "evidence": ["unnumbered paragraph_title on page 1 outside title zone: RESUMEN"], "seed_role": "section_heading", "seed_confidence": 0.5, "seed_evidence": ["unnumbered paragraph_title on page 1 outside title zone: RESUMEN"], "span_metadata": [{"size": 9.962599754333496, "font": "CMCSC10", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}], "raw_observation": {"block_id": 18, "page": 1, "raw_label": "paragraph_title", "text": "RESUMEN", "bbox": [442, 924, 534, 944], "page_width": 1225, "page_height": 1582}, "marker_signature": {"type": "short_fragment", "raw_marker": "RESUMEN", "number": null, "kind": "short_fragment", "normalized_text": "RESUMEN"}, "layout_signature": {"width": 92, "width_bucket": 100, "height": 20, "left": 442, "top": 924, "right": 534, "bottom": 944, "x_center": 488.0, "x_center_bucket": 500, "y_center": 934.0, "x_ratio": 0.3984, "y_ratio": 0.5904, "width_ratio": 0.0751, "height_ratio": 0.0126, "line_count": 1}, "span_signature": {"font_size": 9.96, "font_size_median": 9.96, "font_size_bucket": 10.0, "font_family_norm": "CMCSC10", "bold": false, "italic": true, "span_count": 1}, "_in_visual_container": null, "_container_bbox": null, "_container_text": null, "_text_source": null, "_ocr_raw_status": null, "_ocr_raw_error_type": null, "render_default": true, "index_default": true, "zone": "body_zone", "style_family": "heading_like", "style_family_authority": "heading_typography", "reading_band_id": "band_062", "display_cluster_candidate_id": "", "layout_region": "reference_candidate", "boundary_before": "weak", "boundary_after": "none", "bridge_eligible": false, "insert_score": {"score": 0.15, "decision": "body", "evidence": ["narrow_width"]}, "role_verification_status": "ACCEPT", "role_source": "accepted_heading", "role_evidence": ["heading verified by heading artifact"]} +{"paper_id": "24YKLTHQ", "page": 1, "block_id": 19, "raw_label": "text", "raw_order": 13, "bbox": [438, 958, 1116, 1385], "text": "La estimulación eléctrica es una terapia no invasiva utilizada para estimular la dinámica de los condrocitos: proliferación, migración, morfología y síntesis molecular. Algunos estudios han evidenciado el rol de la frecuencia en la generación de campos eléctricos; sin embargo, la estimulación eléctrica percibida por el condrocito cuando la frecuencia varia no está bien documentada. Por esto, se implementó un modelo computacional para evaluar la dependencia de la frecuencia de los campos eléctricos que estimulan los condrocitos. Las células fueron modeladas en tres escenarios diferentes: cultivos monocapa, explantes de cartílago y andamios. Los condrocitos fueron estimulados con 100 Vp-p a frecuencias de 0.001, 1, 10, 50, 100 y 1000 kHz. Los resultados mostraron que la frecuencia es un factor relevante para estimular muestras biológicas, ya que los campos eléctricos aumentaron a medida que la frecuencia se incrementó. Además, los condrocitos experimentaron diferentes campos eléctricos tanto en el citoplasma como en el ambiente extracellular. Este modelo provee información relevante acerca de los parámetros eléctricos para estimular células; de hecho, este puede mejorar los procedimientos experimentales, prediciendo la estimulación que mejora la dinámica de los condrocitos. Los campos eléctricos son una herramienta prometedora para mantener ya sea condrocitos bien caracterizados o materiales biomiméticos usados en terapias regenerativas tales como la implantación autóloga para tratar lesiones del cartílago hialino.", "page_width": 1225, "page_height": 1582, "role": "body_paragraph", "role_confidence": 0.6, "evidence": ["default body_paragraph for text label"], "seed_role": "body_paragraph", "seed_confidence": 0.6, "seed_evidence": ["default body_paragraph for text label"], "span_metadata": [{"size": 7.970099925994873, "font": "CMR8", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 7.970099925994873, "font": "CMR8", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 7.970099925994873, "font": "CMR8", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 7.970099925994873, "font": "CMR8", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 7.970099925994873, "font": "CMR8", "flags": 4, "color": 0, 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Algunos estudios han evidenciado el rol de la frecuencia en la generación de campos eléctricos; sin embargo, la estimulación eléctrica percibida por el condrocito cuando la frecuencia varia no está bien documentada. Por esto, se implementó un modelo computacional para evaluar la dependencia de la frecuencia de los campos eléctricos que estimulan los condrocitos. Las células fueron modeladas en tres escenarios diferentes: cultivos monocapa, explantes de cartílago y andamios. Los condrocitos fueron estimulados con 100 Vp-p a frecuencias de 0.001, 1, 10, 50, 100 y 1000 kHz. Los resultados mostraron que la frecuencia es un factor relevante para estimular muestras biológicas, ya que los campos eléctricos aumentaron a medida que la frecuencia se incrementó. Además, los condrocitos experimentaron diferentes campos eléctricos tanto en el citoplasma como en el ambiente extracellular. Este modelo provee información relevante acerca de los parámetros eléctricos para estimular células; de hecho, este puede mejorar los procedimientos experimentales, prediciendo la estimulación que mejora la dinámica de los condrocitos. Los campos eléctricos son una herramienta prometedora para mantener ya sea condrocitos bien caracterizados o materiales biomiméticos usados en terapias regenerativas tales como la implantación autóloga para tratar lesiones del cartílago hialino.", "bbox": [438, 958, 1116, 1385], "page_width": 1225, "page_height": 1582}, "marker_signature": {"type": "none", "raw_marker": null, "number": null, "kind": "generic_text", "normalized_text": "La estimulación eléctrica es una terapia no invasiva utilizada para estimular la dinámica de los condrocitos: proliferación, migración, morfología y síntesis molecular. Algunos estudios han evidenciado el rol de la frecuencia en la generación de campos eléctricos; sin embargo, la estimulación eléctrica percibida por el condrocito cuando la frecuencia varia no está bien documentada. Por esto, se implementó un modelo computacional para evaluar la dependencia de la frecuencia de los campos eléctricos que estimulan los condrocitos. Las células fueron modeladas en tres escenarios diferentes: cultivos monocapa, explantes de cartílago y andamios. Los condrocitos fueron estimulados con 100 Vp-p a frecuencias de 0.001, 1, 10, 50, 100 y 1000 kHz. Los resultados mostraron que la frecuencia es un factor relevante para estimular muestras biológicas, ya que los campos eléctricos aumentaron a medida que la frecuencia se incrementó. Además, los condrocitos experimentaron diferentes campos eléctricos tanto en el citoplasma como en el ambiente extracellular. Este modelo provee información relevante acerca de los parámetros eléctricos para estimular células; de hecho, este puede mejorar los procedimientos experimentales, prediciendo la estimulación que mejora la dinámica de los condrocitos. Los campos eléctricos son una herramienta prometedora para mantener ya sea condrocitos bien caracterizados o materiales biomiméticos usados en terapias regenerativas tales como la implantación autóloga para tratar lesiones del cartílago hialino."}, "layout_signature": {"width": 678, "width_bucket": 675, "height": 427, "left": 438, "top": 958, "right": 1116, "bottom": 1385, "x_center": 777.0, "x_center_bucket": 775, "y_center": 1171.5, "x_ratio": 0.6343, "y_ratio": 0.7405, "width_ratio": 0.5535, "height_ratio": 0.2699, "line_count": 1}, "span_signature": {"font_size": 7.97, "font_size_median": 7.97, "font_size_bucket": 8.0, "font_family_norm": "CMR8", "bold": false, "italic": true, "span_count": 390}, "_in_visual_container": null, "_container_bbox": null, "_container_text": null, "_text_source": null, "_ocr_raw_status": null, "_ocr_raw_error_type": null, "render_default": true, "index_default": true, "zone": "body_zone", "style_family": "body_like", "style_family_authority": "body_zone_with_anchor", "reading_band_id": "band_062", "display_cluster_candidate_id": "", "layout_region": "reference_candidate", "boundary_before": "weak", "boundary_after": "none", "bridge_eligible": false, "insert_score": {"score": 0.0, "decision": "body", "evidence": []}, "role_verification_status": "ACCEPT", "role_source": "non_structural_normalized_role", "role_evidence": ["pre-gate normalized non-structural role preserved"]} +{"paper_id": "24YKLTHQ", "page": 1, "block_id": 20, "raw_label": "footnote", "raw_order": null, "bbox": [137, 1385, 1086, 1406], "text": " $ ^{1} $School of Health and Sports Sciences, Fundación Universitaria del Área Andina, Bogotá, Colombia. 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This cell is responsible for synthesizing the main macromolecules located in the cartilaginous tissue: collagen and proteoglycans [2]. Hyaline cartilage is located in two specialized structures of long bones: articular cartilage and growth plate [3–5]. The former acts as a smooth, lubricated and low friction surface that supports mechanical loads and it facilitates the movement between joints [1,6], while the latter structure is responsible for the longitudinal growth and the shape of long bones [6]. 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This cell is responsible for synthesizing the main macromolecules located in the cartilaginous tissue: collagen and proteoglycans [2]. Hyaline cartilage is located in two specialized structures of long bones: articular cartilage and growth plate [3–5]. The former acts as a smooth, lubricated and low friction surface that supports mechanical loads and it facilitates the movement between joints [1,6], while the latter structure is responsible for the longitudinal growth and the shape of long bones [6]. Considering that hyaline cartilage is exposed to a combination of mechanical loads, its avascularity and low proliferative capacity are counterproductive factors that limit the self-healing process of the tissue [7,8].", "bbox": [106, 204, 607, 566], "page_width": 1225, "page_height": 1582}, "marker_signature": {"type": "none", "raw_marker": null, "number": null, "kind": "generic_text", "normalized_text": "Hyaline cartilage is an avascular tissue composed by a single cell type, the chondrocyte [1]. This cell is responsible for synthesizing the main macromolecules located in the cartilaginous tissue: collagen and proteoglycans [2]. Hyaline cartilage is located in two specialized structures of long bones: articular cartilage and growth plate [3–5]. The former acts as a smooth, lubricated and low friction surface that supports mechanical loads and it facilitates the movement between joints [1,6], while the latter structure is responsible for the longitudinal growth and the shape of long bones [6]. Considering that hyaline cartilage is exposed to a combination of mechanical loads, its avascularity and low proliferative capacity are counterproductive factors that limit the self-healing process of the tissue [7,8]."}, "layout_signature": {"width": 501, "width_bucket": 500, "height": 362, "left": 106, "top": 204, "right": 607, "bottom": 566, "x_center": 356.5, "x_center_bucket": 350, "y_center": 385.0, "x_ratio": 0.291, "y_ratio": 0.2434, "width_ratio": 0.409, "height_ratio": 0.2288, "line_count": 1}, "span_signature": {"font_size": 9.96, "font_size_median": 9.96, "font_size_bucket": 10.0, "font_family_norm": "CMR10", "bold": false, "italic": true, "span_count": 217}, "_in_visual_container": null, "_container_bbox": null, "_container_text": null, "_text_source": null, "_ocr_raw_status": null, "_ocr_raw_error_type": null, "render_default": true, "index_default": true, "zone": "body_zone", "style_family": "body_like", "style_family_authority": "body_family_anchor", "reading_band_id": "band_064", "display_cluster_candidate_id": "", "layout_region": "reference_candidate", "boundary_before": "weak", "boundary_after": "none", "bridge_eligible": false, "insert_score": {"score": 0.15, "decision": "body", "evidence": ["narrow_width"]}, "role_verification_status": "ACCEPT", "role_source": "non_structural_normalized_role", "role_evidence": ["pre-gate normalized non-structural role preserved"]} +{"paper_id": "24YKLTHQ", "page": 2, "block_id": 4, "raw_label": "text", "raw_order": 3, "bbox": [106, 589, 606, 1264], "text": "Considering that hyaline cartilage responds to external biophysical stimuli, it has been demonstrated that tissue dynamics are modified when electric fields (EFs) are applied. For instance, in vitro assays have assessed the effect of EFs on chondrocyte behavior within the hyaline cartilage using different culture systems such as monolayer cultures, cartilage explants and tridimensional constructs [9–23]. These studies focused on the assessment of viability, proliferation, synthesis of extracellular matrix components and morphological changes of chondrocytes. However, there are discrepancies in the obtained results, since there are limitations in the adequate frequency to apply the EFs, the voltage required to generate the EFs, the stimulation times and the amount of days that the cultures need to be under stimulation. Moreover, the methodology to calculate, generate and homogeneously distribute the EFs remains a largely unexplored field. Accordingly, different computational approaches have been implemented to assess the effect generated by the application of EFs to cells. For instance, mathematical models were developed to observe the membrane potential in a spherical cell suspended in an electrolyte medium. Results evidenced that induced potential decreases due to surface conductance in small cells, while for bigger cells this potential decreases due to membrane conductance [24]. On the other hand, an electrolyte medium with low conductivity increases.", "page_width": 1225, "page_height": 1582, "role": "body_paragraph", "role_confidence": 0.6, "evidence": ["default body_paragraph for text label"], "seed_role": "body_paragraph", "seed_confidence": 0.6, "seed_evidence": ["default body_paragraph for text label"], "span_metadata": [{"size": 9.962599754333496, "font": "CMR10", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 9.962599754333496, "font": "CMR10", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 9.962599754333496, "font": "CMR10", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 9.962599754333496, "font": "CMR10", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 9.962599754333496, "font": "CMR10", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 9.962599754333496, "font": "CMR10", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 9.962599754333496, "font": 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For instance, in vitro assays have assessed the effect of EFs on chondrocyte behavior within the hyaline cartilage using different culture systems such as monolayer cultures, cartilage explants and tridimensional constructs [9–23]. These studies focused on the assessment of viability, proliferation, synthesis of extracellular matrix components and morphological changes of chondrocytes. However, there are discrepancies in the obtained results, since there are limitations in the adequate frequency to apply the EFs, the voltage required to generate the EFs, the stimulation times and the amount of days that the cultures need to be under stimulation. Moreover, the methodology to calculate, generate and homogeneously distribute the EFs remains a largely unexplored field. Accordingly, different computational approaches have been implemented to assess the effect generated by the application of EFs to cells. For instance, mathematical models were developed to observe the membrane potential in a spherical cell suspended in an electrolyte medium. Results evidenced that induced potential decreases due to surface conductance in small cells, while for bigger cells this potential decreases due to membrane conductance [24]. On the other hand, an electrolyte medium with low conductivity increases.", "bbox": [106, 589, 606, 1264], "page_width": 1225, "page_height": 1582}, "marker_signature": {"type": "none", "raw_marker": null, "number": null, "kind": "generic_text", "normalized_text": "Considering that hyaline cartilage responds to external biophysical stimuli, it has been demonstrated that tissue dynamics are modified when electric fields (EFs) are applied. For instance, in vitro assays have assessed the effect of EFs on chondrocyte behavior within the hyaline cartilage using different culture systems such as monolayer cultures, cartilage explants and tridimensional constructs [9–23]. These studies focused on the assessment of viability, proliferation, synthesis of extracellular matrix components and morphological changes of chondrocytes. However, there are discrepancies in the obtained results, since there are limitations in the adequate frequency to apply the EFs, the voltage required to generate the EFs, the stimulation times and the amount of days that the cultures need to be under stimulation. Moreover, the methodology to calculate, generate and homogeneously distribute the EFs remains a largely unexplored field. Accordingly, different computational approaches have been implemented to assess the effect generated by the application of EFs to cells. For instance, mathematical models were developed to observe the membrane potential in a spherical cell suspended in an electrolyte medium. Results evidenced that induced potential decreases due to surface conductance in small cells, while for bigger cells this potential decreases due to membrane conductance [24]. On the other hand, an electrolyte medium with low conductivity increases."}, "layout_signature": {"width": 500, "width_bucket": 500, "height": 675, "left": 106, "top": 589, "right": 606, "bottom": 1264, "x_center": 356.0, "x_center_bucket": 350, "y_center": 926.5, "x_ratio": 0.2906, "y_ratio": 0.5857, "width_ratio": 0.4082, "height_ratio": 0.4267, "line_count": 1}, "span_signature": {"font_size": 9.96, "font_size_median": 9.96, "font_size_bucket": 10.0, "font_family_norm": "CMR10", "bold": false, "italic": true, "span_count": 375}, "_in_visual_container": null, "_container_bbox": null, "_container_text": null, "_text_source": null, "_ocr_raw_status": null, "_ocr_raw_error_type": null, "render_default": true, "index_default": true, "zone": "body_zone", "style_family": "body_like", "style_family_authority": "body_family_anchor", "reading_band_id": "band_065", "display_cluster_candidate_id": "", "layout_region": "reference_candidate", "boundary_before": "weak", "boundary_after": "none", "bridge_eligible": false, "insert_score": {"score": 0.15, "decision": "body", "evidence": ["narrow_width"]}, "role_verification_status": "ACCEPT", "role_source": "non_structural_normalized_role", "role_evidence": ["pre-gate normalized non-structural role preserved"]} +{"paper_id": "24YKLTHQ", "page": 2, "block_id": 5, "raw_label": "text", "raw_order": 4, "bbox": [106, 1262, 606, 1432], "text": "the charging time of the cell membrane; therefore, cells immersed in this kind of medium need to be stimulated with higher EFs to induce electroporation in the cell membrane [25]. In a study carried out by Krassowska et al., the polarization and physiological state of a single cell electrically stimulated was modeled [26]. A similar study analyzed the variation of the transmembrane potential on prolate and oblate spheroidal cells stimulated with EFs. Results evidenced that the transmembrane potential strongly depends on the cell orientation when a cell is being stimulated [27]. Similarly, computational models to simulate the effect of alternating current EFs on spheroidal cells were implemented. Results indicated that time-dependent geometry changes influence the induced membrane potential of the cell; additionally, the time-dependent charging and discharging of the membrane can be modeled when the frequency dependence is transformed into a time dependence [28,29].", "page_width": 1225, "page_height": 1582, "role": "body_paragraph", "role_confidence": 0.6, "evidence": ["default body_paragraph for text label"], "seed_role": "body_paragraph", "seed_confidence": 0.6, "seed_evidence": ["default body_paragraph for text label"], "span_metadata": [{"size": 9.962599754333496, "font": "CMR10", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 9.962599754333496, "font": "CMR10", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 9.962599754333496, "font": "CMR10", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 9.962599754333496, "font": "CMR10", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 9.962599754333496, "font": 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In a study carried out by Krassowska et al., the polarization and physiological state of a single cell electrically stimulated was modeled [26]. A similar study analyzed the variation of the transmembrane potential on prolate and oblate spheroidal cells stimulated with EFs. Results evidenced that the transmembrane potential strongly depends on the cell orientation when a cell is being stimulated [27]. Similarly, computational models to simulate the effect of alternating current EFs on spheroidal cells were implemented. Results indicated that time-dependent geometry changes influence the induced membrane potential of the cell; additionally, the time-dependent charging and discharging of the membrane can be modeled when the frequency dependence is transformed into a time dependence [28,29].", "bbox": [106, 1262, 606, 1432], "page_width": 1225, "page_height": 1582}, "marker_signature": {"type": "none", "raw_marker": null, "number": null, "kind": "generic_text", "normalized_text": "the charging time of the cell membrane; therefore, cells immersed in this kind of medium need to be stimulated with higher EFs to induce electroporation in the cell membrane [25]. In a study carried out by Krassowska et al., the polarization and physiological state of a single cell electrically stimulated was modeled [26]. A similar study analyzed the variation of the transmembrane potential on prolate and oblate spheroidal cells stimulated with EFs. Results evidenced that the transmembrane potential strongly depends on the cell orientation when a cell is being stimulated [27]. Similarly, computational models to simulate the effect of alternating current EFs on spheroidal cells were implemented. Results indicated that time-dependent geometry changes influence the induced membrane potential of the cell; additionally, the time-dependent charging and discharging of the membrane can be modeled when the frequency dependence is transformed into a time dependence [28,29]."}, "layout_signature": {"width": 500, "width_bucket": 500, "height": 170, "left": 106, "top": 1262, "right": 606, "bottom": 1432, "x_center": 356.0, "x_center_bucket": 350, "y_center": 1347.0, "x_ratio": 0.2906, "y_ratio": 0.8515, "width_ratio": 0.4082, "height_ratio": 0.1075, "line_count": 1}, "span_signature": {"font_size": 9.96, "font_size_median": 9.96, "font_size_bucket": 10.0, "font_family_norm": "CMR10", "bold": false, "italic": true, "span_count": 108}, "_in_visual_container": null, "_container_bbox": null, "_container_text": null, "_text_source": null, "_ocr_raw_status": null, "_ocr_raw_error_type": null, "render_default": true, "index_default": true, "zone": "body_zone", "style_family": "body_like", 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"_ocr_raw_error_type": "backfill_overlaps_existing_text_block", "render_default": true, "index_default": true, "zone": "body_zone", "style_family": "body_like", "style_family_authority": "body_zone_with_anchor", "_needs_pdf_fallback": true, "reading_band_id": "band_060", "display_cluster_candidate_id": "", "layout_region": "reference_candidate", "boundary_before": "weak", "boundary_after": "none", "bridge_eligible": false, "insert_score": {"score": 0.15, "decision": "body", "evidence": ["narrow_width"]}, "role_verification_status": "ACCEPT", "role_source": "non_structural_normalized_role", "role_evidence": ["pre-gate normalized non-structural role preserved"]} +{"paper_id": "24YKLTHQ", "page": 2, "block_id": 7, "raw_label": "text", "raw_order": 6, "bbox": [614, 470, 1118, 1428], "text": "Even though the computational models evidenced that transmembrane potential vary according to cell shape, size and orientation, the models did not consider different frequencies and dielectric properties of the in vivo extracellular environment where the cell is located such as living tissues and three-dimensional structures. The computational model that has evaluated the effect of external EFs on a single cell cultured in monolayer was developed by Taghian et al., [30]. The results showed that the cell membrane behavior of the cell strongly depends on the frequency applied; however, the computational analysis was performed using a one-dimensional round cell morphology in one of the possible scenarios where a cell may grow. In this context, the role of the frequency and extracellular matrix in terms of distribution of EFs around and within the cell has not been well-documented. For this reason, we hypothesize that a computational model may estimate the EFs sensed by the cells according to the environment where they are located. To prove this hypothesis, a finite element model was implemented to simulate chondrocytes cultured in three different scenarios: 1) a cell cultured in monolayer and surrounded by culture media [22], 2) a chondrocyte within a cartilage explant of two day-old bone rat [21], and 3) a cell inside of a chondrogenic scaffold composed by two biopolymers such as hyaluronic acid and gelatin [31]. The computational model was simulated to mimic the stimulation of a biological sample using two external stainless-steel electrodes located at the bottom and upper surface of a culture well plate. Result evidenced that the EFs sensed by the cells are frequency-dependent, since at higher frequencies the EFs are higher. Moreover, it was possible to determine that the EFs in cells cultured in monolayer is different intra and extracellularly, since the EFs near to the cell membrane are higher than the EFs in the cytoplasm of the cell. Additionally, the EFs sensed by the chondrocytes located at different positions within the explant were different. The EFs that stimulated cells in the superficial part of the explant were higher compared with the EFs perceived by the chondrocytes located close", "page_width": 1225, "page_height": 1582, "role": "body_paragraph", "role_confidence": 0.6, "evidence": ["default body_paragraph for text label"], "seed_role": "body_paragraph", "seed_confidence": 0.6, "seed_evidence": ["default body_paragraph for text label"], "span_metadata": [{"size": 9.962599754333496, "font": "CMR10", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 9.962599754333496, "font": "CMR10", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 9.962599754333496, "font": "CMR10", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 9.962599754333496, "font": "CMR10", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 9.962599754333496, "font": "CMR10", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 9.962599754333496, "font": "CMR10", "flags": 4, "color": 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The computational model that has evaluated the effect of external EFs on a single cell cultured in monolayer was developed by Taghian et al., [30]. The results showed that the cell membrane behavior of the cell strongly depends on the frequency applied; however, the computational analysis was performed using a one-dimensional round cell morphology in one of the possible scenarios where a cell may grow. In this context, the role of the frequency and extracellular matrix in terms of distribution of EFs around and within the cell has not been well-documented. For this reason, we hypothesize that a computational model may estimate the EFs sensed by the cells according to the environment where they are located. To prove this hypothesis, a finite element model was implemented to simulate chondrocytes cultured in three different scenarios: 1) a cell cultured in monolayer and surrounded by culture media [22], 2) a chondrocyte within a cartilage explant of two day-old bone rat [21], and 3) a cell inside of a chondrogenic scaffold composed by two biopolymers such as hyaluronic acid and gelatin [31]. The computational model was simulated to mimic the stimulation of a biological sample using two external stainless-steel electrodes located at the bottom and upper surface of a culture well plate. Result evidenced that the EFs sensed by the cells are frequency-dependent, since at higher frequencies the EFs are higher. Moreover, it was possible to determine that the EFs in cells cultured in monolayer is different intra and extracellularly, since the EFs near to the cell membrane are higher than the EFs in the cytoplasm of the cell. Additionally, the EFs sensed by the chondrocytes located at different positions within the explant were different. The EFs that stimulated cells in the superficial part of the explant were higher compared with the EFs perceived by the chondrocytes located close", "bbox": [614, 470, 1118, 1428], "page_width": 1225, "page_height": 1582}, "marker_signature": {"type": "none", "raw_marker": null, "number": null, "kind": "generic_text", "normalized_text": "Even though the computational models evidenced that transmembrane potential vary according to cell shape, size and orientation, the models did not consider different frequencies and dielectric properties of the in vivo extracellular environment where the cell is located such as living tissues and three-dimensional structures. The computational model that has evaluated the effect of external EFs on a single cell cultured in monolayer was developed by Taghian et al., [30]. The results showed that the cell membrane behavior of the cell strongly depends on the frequency applied; however, the computational analysis was performed using a one-dimensional round cell morphology in one of the possible scenarios where a cell may grow. In this context, the role of the frequency and extracellular matrix in terms of distribution of EFs around and within the cell has not been well-documented. For this reason, we hypothesize that a computational model may estimate the EFs sensed by the cells according to the environment where they are located. To prove this hypothesis, a finite element model was implemented to simulate chondrocytes cultured in three different scenarios: 1) a cell cultured in monolayer and surrounded by culture media [22], 2) a chondrocyte within a cartilage explant of two day-old bone rat [21], and 3) a cell inside of a chondrogenic scaffold composed by two biopolymers such as hyaluronic acid and gelatin [31]. The computational model was simulated to mimic the stimulation of a biological sample using two external stainless-steel electrodes located at the bottom and upper surface of a culture well plate. Result evidenced that the EFs sensed by the cells are frequency-dependent, since at higher frequencies the EFs are higher. Moreover, it was possible to determine that the EFs in cells cultured in monolayer is different intra and extracellularly, since the EFs near to the cell membrane are higher than the EFs in the cytoplasm of the cell. Additionally, the EFs sensed by the chondrocytes located at different positions within the explant were different. The EFs that stimulated cells in the superficial part of the explant were higher compared with the EFs perceived by the chondrocytes located close"}, "layout_signature": {"width": 504, "width_bucket": 500, "height": 958, "left": 614, "top": 470, "right": 1118, "bottom": 1428, "x_center": 866.0, "x_center_bucket": 875, "y_center": 949.0, "x_ratio": 0.7069, "y_ratio": 0.5999, "width_ratio": 0.4114, "height_ratio": 0.6056, "line_count": 1}, "span_signature": {"font_size": 9.96, "font_size_median": 9.96, "font_size_bucket": 10.0, "font_family_norm": "CMR10", "bold": false, "italic": true, "span_count": 503}, "_in_visual_container": null, "_container_bbox": null, "_container_text": null, "_text_source": null, "_ocr_raw_status": null, "_ocr_raw_error_type": null, "render_default": true, "index_default": true, "zone": "body_zone", "style_family": "body_like", "style_family_authority": "body_zone_with_anchor", "reading_band_id": "band_060", "display_cluster_candidate_id": "", "layout_region": 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The findings derived from this computational model could be used to estimate the EFs desired to trigger intracellular responses from the cell. In fact, it has been reported that external EFs modifies the ionic fluid flow of the cell membrane; for this reason, this computational model may be a useful tool to improve experimental procedures. For instance, the model could predict the field strength and frequency that stimulate the cell membrane receptors such as ionic transmembrane channels responsible for activating different signaling pathways within the cell cytoplasm.", "page_width": 1225, "page_height": 1582, "role": "body_paragraph", "role_confidence": 0.6, "evidence": ["default body_paragraph for text label"], "seed_role": "body_paragraph", "seed_confidence": 0.6, "seed_evidence": ["default body_paragraph for text label"], "span_metadata": [{"size": 9.962599754333496, "font": "CMR10", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 9.962599754333496, "font": "CMR10", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 9.962599754333496, "font": "CMR10", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 9.962599754333496, "font": "CMR10", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 9.962599754333496, "font": "CMR10", "flags": 4, "color": 0, "dir": [1.0, 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The findings derived from this computational model could be used to estimate the EFs desired to trigger intracellular responses from the cell. In fact, it has been reported that external EFs modifies the ionic fluid flow of the cell membrane; for this reason, this computational model may be a useful tool to improve experimental procedures. For instance, the model could predict the field strength and frequency that stimulate the cell membrane receptors such as ionic transmembrane channels responsible for activating different signaling pathways within the cell cytoplasm.", "bbox": [106, 144, 606, 410], "page_width": 1225, "page_height": 1582}, "marker_signature": {"type": "none", "raw_marker": null, "number": null, "kind": "generic_text", "normalized_text": "to the ossification of the explant. The findings derived from this computational model could be used to estimate the EFs desired to trigger intracellular responses from the cell. 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The capacitive coupled system is composed of two parallel stainless-steel electrodes, which are located at the top and bottom of a culture well plate. Both culture media and biological samples were placed within the culture well plate, respectively (Figure 1). In this study, biological samples were modelled using two different well plate dimensions according to previous experimental procedures performed in our laboratory [21, 22, 32]. The single cell and the cartilage explant were simulated in a 6 well plate, while the chondrogenic scaffolds was modelled in a 48 well plate. The dimensions of the different materials that compose the capacitive system are listed in Table 1, while their dielectric properties, i.e. relative permittivity ( $ \\epsilon $) and electric conductivity ( $ \\sigma $), are shown in Table 2. The boundary conditions for electric simulations consisted on a temperature of 310 K and a standard atmospheric pressure of 1 atm. 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In this study, biological samples were modelled using two different well plate dimensions according to previous experimental procedures performed in our laboratory [21, 22, 32]. The single cell and the cartilage explant were simulated in a 6 well plate, while the chondrogenic scaffolds was modelled in a 48 well plate. The dimensions of the different materials that compose the capacitive system are listed in Table 1, while their dielectric properties, i.e. relative permittivity ( $ \\epsilon $) and electric conductivity ( $ \\sigma $), are shown in Table 2. The boundary conditions for electric simulations consisted on a temperature of 310 K and a standard atmospheric pressure of 1 atm. The EFs were generated by applying 100 Vp-p at frequencies of 0.001, 1, 10, 50, 100 and 1000 kHz sine-wave form. 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Radius50 [mm]
Thickness5 [mm]
$ \\varepsilon $1
$ \\sigma $1.73 [MS/m]
Well plateThickness1 [mm][21], [31]
Height20 [mm]
Radius48 well plate 6 [mm]6 well plate 17.5 [mm]
$ \\varepsilon $3.5
$ \\sigma $6.6 $ \\times $ 10 $ ^{-16} $ [S/m]
Air$ \\varepsilon $1[21]
$ \\sigma $0 [S/m]
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ComponentParameterValueReference
Stainless-steel electrodeSeparation20 [mm][21]
Radius50 [mm]
Thickness5 [mm]
$ \\varepsilon $1
$ \\sigma $1.73 [MS/m]
Well plateThickness1 [mm][21], [31]
Height20 [mm]
Radius48 well plate 6 [mm]6 well plate 17.5 [mm]
$ \\varepsilon $3.5
$ \\sigma $6.6 $ \\times $ 10 $ ^{-16} $ [S/m]
Air$ \\varepsilon $1[21]
$ \\sigma $0 [S/m]
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ComponentParameterValueReference
Stainless-steel electrodeSeparation20 [mm][21]
Radius50 [mm]
Thickness5 [mm]
$ \\varepsilon $1
$ \\sigma $1.73 [MS/m]
Well plateThickness1 [mm][21], [31]
Height20 [mm]
Radius48 well plate 6 [mm]6 well plate 17.5 [mm]
$ \\varepsilon $3.5
$ \\sigma $6.6 $ \\times $ 10 $ ^{-16} $ [S/m]
Air$ \\varepsilon $1[21]
$ \\sigma $0 [S/m]
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Frequency (kHz)Reference
0.01110501001000
Cell$ \\varepsilon $74.3[33]
$ \\sigma $ [S/m]1.02
Cartilage$ \\varepsilon $2.0E+073.2E+044.04E+032.7E+032.5E+031.3E+03[34]
$ \\sigma $ [S/m]1.6E-011.7E-011.76E-011.7E-011.9E-012.3E-01
Bone$ \\varepsilon $1.0E+065.6E+036.76E+021.8E+021.1E+023.8E+01
$ \\sigma $ [S/m]9.7E-042.2E-032.73E-033.3E-033.2E-034.1E-03
Scaffold$ \\varepsilon $3.3E+061.8E+054.81E+048.6E+033.2E+039.2E+02[31]
$ \\sigma $ [S/m]2.1E-031.1E-023.64E-027.0E-028.6E-021.1E-01
Culture$ \\varepsilon $1.6E+061.2E+055.77E+042.7E+041.1E+042.5E+03
media$ \\sigma $ [S/m]1.6E-024.5E-031.78E-026.8E-021.7E-013.4E-01
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Frequency (kHz)Reference
0.01110501001000
Cell$ \\varepsilon $74.3[33]
$ \\sigma $ [S/m]1.02
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$ \\sigma $ [S/m]1.6E-011.7E-011.76E-011.7E-011.9E-012.3E-01
Bone$ \\varepsilon $1.0E+065.6E+036.76E+021.8E+021.1E+023.8E+01
$ \\sigma $ [S/m]9.7E-042.2E-032.73E-033.3E-033.2E-034.1E-03
Scaffold$ \\varepsilon $3.3E+061.8E+054.81E+048.6E+033.2E+039.2E+02[31]
$ \\sigma $ [S/m]2.1E-031.1E-023.64E-027.0E-028.6E-021.1E-01
Culture$ \\varepsilon $1.6E+061.2E+055.77E+042.7E+041.1E+042.5E+03
media$ \\sigma $ [S/m]1.6E-024.5E-031.78E-026.8E-021.7E-013.4E-01
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Frequency (kHz)Reference
0.01110501001000
Cell$ \\varepsilon $74.3[33]
$ \\sigma $ [S/m]1.02
Cartilage$ \\varepsilon $2.0E+073.2E+044.04E+032.7E+032.5E+031.3E+03[34]
$ \\sigma $ [S/m]1.6E-011.7E-011.76E-011.7E-011.9E-012.3E-01
Bone$ \\varepsilon $1.0E+065.6E+036.76E+021.8E+021.1E+023.8E+01
$ \\sigma $ [S/m]9.7E-042.2E-032.73E-033.3E-033.2E-034.1E-03
Scaffold$ \\varepsilon $3.3E+061.8E+054.81E+048.6E+033.2E+039.2E+02[31]
$ \\sigma $ [S/m]2.1E-031.1E-023.64E-027.0E-028.6E-021.1E-01
Culture$ \\varepsilon $1.6E+061.2E+055.77E+042.7E+041.1E+042.5E+03
media$ \\sigma $ [S/m]1.6E-024.5E-031.78E-026.8E-021.7E-013.4E-01
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simulated (Figure 2A). The chondrocyte, completely attached to the bottom of a 6 well plate, was modelled considering an ellipsoidal morphology. Cell dimensions were 9 μm of length and 1 μm of height [35], while dielectric constants used for the cell are described in table 2. The domain was meshed using triangular elements obtaining 136,542 elements.", "bbox": [106, 1101, 606, 1293], "page_width": 1225, "page_height": 1582}, "marker_signature": {"type": "none", "raw_marker": null, "number": null, "kind": "generic_text", "normalized_text": "An axisymmetric monolayer culture with a single chondrocyte was simulated (Figure 2A). The chondrocyte, completely attached to the bottom of a 6 well plate, was modelled considering an ellipsoidal morphology. Cell dimensions were 9 μm of length and 1 μm of height [35], while dielectric constants used for the cell are described in table 2. The domain was meshed using triangular elements obtaining 136,542 elements."}, "layout_signature": {"width": 500, "width_bucket": 500, "height": 192, "left": 106, "top": 1101, "right": 606, "bottom": 1293, "x_center": 356.0, "x_center_bucket": 350, "y_center": 1197.0, "x_ratio": 0.2906, "y_ratio": 0.7566, "width_ratio": 0.4082, "height_ratio": 0.1214, "line_count": 1}, "span_signature": {"font_size": 9.96, "font_size_median": 9.96, "font_size_bucket": 10.0, "font_family_norm": "CMR10", "bold": true, "italic": true, "span_count": 123}, "_in_visual_container": null, "_container_bbox": null, "_container_text": null, "_text_source": null, "_ocr_raw_status": null, "_ocr_raw_error_type": null, "render_default": true, "index_default": true, "zone": "body_zone", "style_family": "body_like", "style_family_authority": "body_family_anchor", "reading_band_id": "band_060", "display_cluster_candidate_id": "", "layout_region": "reference_candidate", "boundary_before": "weak", "boundary_after": "none", "bridge_eligible": false, "insert_score": {"score": 0.15, "decision": "body", "evidence": ["narrow_width"]}, "role_verification_status": "ACCEPT", "role_source": "non_structural_normalized_role", "role_evidence": ["pre-gate normalized non-structural role preserved"]} +{"paper_id": "24YKLTHQ", "page": 4, "block_id": 10, "raw_label": "paragraph_title", "raw_order": 3, "bbox": [108, 1328, 579, 1353], "text": "2.3. 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The scaffold was simulated as a drop with a radius of 3.5 mm with chondrocytes of 10 $ \\mu $m located at the bottom, middle and upper surface of the three-dimensional construct (Figure 2C). The dielectric properties of the cell and scaffold are shown in table 2. 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The scaffold was simulated as a drop with a radius of 3.5 mm with chondrocytes of 10 $ \\mu $m located at the bottom, middle and upper surface of the three-dimensional construct (Figure 2C). The dielectric properties of the cell and scaffold are shown in table 2. The domain was meshed using triangle elements obtaining 136,976 elements.", "bbox": [107, 145, 607, 313], "page_width": 1225, "page_height": 1582}, "marker_signature": {"type": "none", "raw_marker": null, "number": null, "kind": "generic_text", "normalized_text": "and gelatin. The scaffold was simulated as a drop with a radius of 3.5 mm with chondrocytes of 10 $ \\mu $m located at the bottom, middle and upper surface of the three-dimensional construct (Figure 2C). The dielectric properties of the cell and scaffold are shown in table 2. The domain was meshed using triangle elements obtaining 136,976 elements."}, "layout_signature": {"width": 500, "width_bucket": 500, "height": 168, "left": 107, "top": 145, "right": 607, "bottom": 313, "x_center": 357.0, "x_center_bucket": 350, "y_center": 229.0, "x_ratio": 0.2914, "y_ratio": 0.1448, "width_ratio": 0.4082, "height_ratio": 0.1062, "line_count": 1}, "span_signature": {"font_size": 9.96, "font_size_median": 9.96, "font_size_bucket": 10.0, "font_family_norm": "CMR10", "bold": true, "italic": true, "span_count": 110}, "_in_visual_container": null, "_container_bbox": null, "_container_text": null, "_text_source": null, "_ocr_raw_status": null, "_ocr_raw_error_type": null, "render_default": true, "index_default": true, "zone": "body_zone", "style_family": "body_like", "style_family_authority": "body_family_anchor", "reading_band_id": "band_064", "display_cluster_candidate_id": "", "layout_region": "reference_candidate", "boundary_before": "weak", "boundary_after": "none", "bridge_eligible": false, "insert_score": {"score": 0.15, "decision": "body", "evidence": ["narrow_width"]}, "role_verification_status": "ACCEPT", "role_source": "non_structural_normalized_role", "role_evidence": ["pre-gate normalized non-structural role preserved"]} +{"paper_id": "24YKLTHQ", "page": 5, "block_id": 3, "raw_label": "text", "raw_order": 2, "bbox": [108, 355, 606, 525], "text": "Figure 2: Meshes of the three different culture systems simulated in the study. A) Culture system used to stimulate a single chondrocyte cultured in monolayer. B) Culture system implemented to stimulate chondrocytes of a cartilage explant cultured in vitro. C) Culture system performed to stimulate chondrocytes embedded in a hyaluronic acid – gelatin scaffold.", "page_width": 1225, "page_height": 1582, "role": "figure_caption", "role_confidence": 0.9, "evidence": ["figure caption candidate (body narrative): Figure 2: Meshes of the three different culture systems simu"], "seed_role": "figure_caption_candidate", "seed_confidence": 0.9, "seed_evidence": ["figure caption candidate (body narrative): Figure 2: Meshes of the three different culture systems simu"], "span_metadata": [{"size": 9.962599754333496, "font": "CMBX10", "flags": 20, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 9.962599754333496, "font": "CMBX10", "flags": 20, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 9.962599754333496, "font": "CMBX10", "flags": 20, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 9.962599754333496, "font": "CMR10", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 9.962599754333496, "font": "CMR10", "flags": 4, 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First, an axisymmetric model was selected to represent the domains of the EF's. Then, the physics to simulate the EF's was solved using the Electric Currents interface from the alternating current (AC) module. Next, the simulation of EF's was carried out in the Frequency Domain study. After that, the domain composed by the well plate, the biological sample, the cell culture media, the air and the electrodes were built. The boundary conditions for each domain, specifically temperature and pressure, were assigned within the model. Once the domains were restricted, the material properties $ \\epsilon $ and $ \\sigma $ were defined for each component of the model. Then, the equation for EF's was defined and inserted into the model to be solved. After, each domain was meshed using triangular elements, followed by a mesh refinement where the cells were located. 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First, an axisymmetric model was selected to represent the domains of the EF's. Then, the physics to simulate the EF's was solved using the Electric Currents interface from the alternating current (AC) module. Next, the simulation of EF's was carried out in the Frequency Domain study. After that, the domain composed by the well plate, the biological sample, the cell culture media, the air and the electrodes were built. The boundary conditions for each domain, specifically temperature and pressure, were assigned within the model. Once the domains were restricted, the material properties $ \\epsilon $ and $ \\sigma $ were defined for each component of the model. Then, the equation for EF's was defined and inserted into the model to be solved. After, each domain was meshed using triangular elements, followed by a mesh refinement where the cells were located. Finally, the model was solved to observe the field flow distribution in the whole domain.", "bbox": [107, 1182, 606, 1448], "page_width": 1225, "page_height": 1582}, "marker_signature": {"type": "none", "raw_marker": null, "number": null, "kind": "generic_text", "normalized_text": "The procedures to simulate the effect generated by EF's on a single cell, a cartilage explant and a scaffold are described in figure 3. First, an axisymmetric model was selected to represent the domains of the EF's. Then, the physics to simulate the EF's was solved using the Electric Currents interface from the alternating current (AC) module. Next, the simulation of EF's was carried out in the Frequency Domain study. After that, the domain composed by the well plate, the biological sample, the cell culture media, the air and the electrodes were built. The boundary conditions for each domain, specifically temperature and pressure, were assigned within the model. Once the domains were restricted, the material properties $ \\epsilon $ and $ \\sigma $ were defined for each component of the model. Then, the equation for EF's was defined and inserted into the model to be solved. After, each domain was meshed using triangular elements, followed by a mesh refinement where the cells were located. 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homogeneous, specially within the chondrocytes and the cell culture media where the cells were attached (Figure 4A). Results evidenced that the EFs tend to increase as the frequency was higher. For instance, the EFs in the culture media at 1 kHz were around 1.8 mV/cm, while EFs at 100 kHz were around 9.2 mV/cm; moreover, a negligible decrease in the EFs was observed from the bottom to the upper surface of", "bbox": [616, 1231, 1117, 1448], "page_width": 1225, "page_height": 1582}, "marker_signature": {"type": "none", "raw_marker": null, "number": null, "kind": "generic_text", "normalized_text": "The flow of the EFs through the monolayer cell culture system is completely homogeneous, specially within the chondrocytes and the cell culture media where the cells were attached (Figure 4A). Results evidenced that the EFs tend to increase as the frequency was higher. For instance, the EFs in the culture media at 1 kHz were around 1.8 mV/cm, while EFs at 100 kHz were around 9.2 mV/cm; moreover, a negligible decrease in the EFs was observed from the bottom to the upper surface of"}, "layout_signature": {"width": 501, "width_bucket": 500, "height": 217, "left": 616, "top": 1231, "right": 1117, "bottom": 1448, "x_center": 866.5, "x_center_bucket": 875, "y_center": 1339.5, "x_ratio": 0.7073, "y_ratio": 0.8467, "width_ratio": 0.409, "height_ratio": 0.1372, "line_count": 1}, "span_signature": {"font_size": 9.96, "font_size_median": 9.96, "font_size_bucket": 10.0, "font_family_norm": "CMR10", "bold": true, "italic": true, "span_count": 102}, "_in_visual_container": null, "_container_bbox": null, "_container_text": null, "_text_source": null, "_ocr_raw_status": null, "_ocr_raw_error_type": null, "render_default": true, "index_default": true, "zone": "body_zone", "style_family": "body_like", "style_family_authority": "body_zone_with_anchor", 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J. VACA-GONZÁLEZ, J. F. ESCOBAR-HUERTAS AND D. A. 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J. VACA-GONZÁLEZ, J. F. ESCOBAR-HUERTAS AND D. A. GARZÓN-ALVARADO", "bbox": [590, 95, 1115, 113], "page_width": 1225, "page_height": 1582}, "marker_signature": {"type": "none", "raw_marker": null, "number": null, "kind": "generic_text", "normalized_text": "J. J. VACA-GONZÁLEZ, J. F. ESCOBAR-HUERTAS AND D. A. 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Regarding the EFs in the cytoplasm of the chondrocyte, EFs of 0.02 mV/cm for 1 kHz were observed, while EFs of 1.9 mV/cm for 100 kHz were perceived (Figure 4C). Finally, the EFs near to the cell membrane of the chondrocyte were 2.4 mV/cm for 1 kHz and 12.1 mV/cm for 100 kHz (Figure 4D). 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Regarding the EFs in the cytoplasm of the chondrocyte, EFs of 0.02 mV/cm for 1 kHz were observed, while EFs of 1.9 mV/cm for 100 kHz were perceived (Figure 4C). Finally, the EFs near to the cell membrane of the chondrocyte were 2.4 mV/cm for 1 kHz and 12.1 mV/cm for 100 kHz (Figure 4D). Monolayer cultures that were stimulated with 1 MGz evidenced similar EFs of 12.5 mV/cm in the cytoplasm of the chondrocyte and in the extracellular environment near to the cell membrane.", "bbox": [106, 145, 607, 384], "page_width": 1225, "page_height": 1582}, "marker_signature": {"type": "none", "raw_marker": null, "number": null, "kind": "generic_text", "normalized_text": "the culture media (Figure 4B). Regarding the EFs in the cytoplasm of the chondrocyte, EFs of 0.02 mV/cm for 1 kHz were observed, while EFs of 1.9 mV/cm for 100 kHz were perceived (Figure 4C). Finally, the EFs near to the cell membrane of the chondrocyte were 2.4 mV/cm for 1 kHz and 12.1 mV/cm for 100 kHz (Figure 4D). Monolayer cultures that were stimulated with 1 MGz evidenced similar EFs of 12.5 mV/cm in the cytoplasm of the chondrocyte and in the extracellular environment near to the cell membrane."}, "layout_signature": {"width": 501, "width_bucket": 500, "height": 239, "left": 106, "top": 145, "right": 607, "bottom": 384, "x_center": 356.5, "x_center_bucket": 350, "y_center": 264.5, "x_ratio": 0.291, "y_ratio": 0.1672, "width_ratio": 0.409, "height_ratio": 0.1511, "line_count": 1}, "span_signature": {"font_size": 9.96, "font_size_median": 9.96, "font_size_bucket": 10.0, "font_family_norm": "CMR10", "bold": true, "italic": true, "span_count": 139}, "_in_visual_container": null, "_container_bbox": null, "_container_text": null, "_text_source": null, "_ocr_raw_status": null, "_ocr_raw_error_type": null, "render_default": true, "index_default": true, "zone": "body_zone", "style_family": "body_like", "style_family_authority": "body_family_anchor", "reading_band_id": "band_064", "display_cluster_candidate_id": "", "layout_region": "reference_candidate", "boundary_before": "weak", "boundary_after": "none", "bridge_eligible": false, "insert_score": {"score": 0.15, "decision": "body", "evidence": ["narrow_width"]}, "role_verification_status": "ACCEPT", "role_source": "non_structural_normalized_role", "role_evidence": ["pre-gate normalized non-structural role preserved"]} +{"paper_id": "24YKLTHQ", "page": 6, "block_id": 3, "raw_label": "paragraph_title", "raw_order": 2, "bbox": [109, 413, 495, 437], "text": "3.2. 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Results evidenced an increase of EFs in stimulated explants as the frequency was higher; in fact, the EFs inside the culture media were the same as reported in monolayer cultures with a negligible decrease of the EFs from the bottom to the upper surface (Figure 5B). The EFs were measured in both bone and cartilage of the explant (Figure 5C). On the one hand, different EF intensities along the bone were observed; for example, EFs of 8.3 mV/cm for 1 kHz and 573 mV/cm for 100 kHz were evidenced at the base of the bone. The EFs in the middle of the bone were 3 mV/cm for 1 kHz and 11.8 mV/cm for 100 kHz. The EFs near the ossification front were 3.9 mV/cm for 1 kHz and EFs 21 mV/cm for 100 kHz (Figure 5D). On the other hand, the EFs intensity through the cartilage tend to be the same; for example, EFs of 0.2 mV/cm for 1 kHz were observed, while EFs of 7.9 mV/cm for 100 kHz were perceived (Figure 5E). 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Results evidenced an increase of EFs in stimulated explants as the frequency was higher; in fact, the EFs inside the culture media were the same as reported in monolayer cultures with a negligible decrease of the EFs from the bottom to the upper surface (Figure 5B). The EFs were measured in both bone and cartilage of the explant (Figure 5C). On the one hand, different EF intensities along the bone were observed; for example, EFs of 8.3 mV/cm for 1 kHz and 573 mV/cm for 100 kHz were evidenced at the base of the bone. The EFs in the middle of the bone were 3 mV/cm for 1 kHz and 11.8 mV/cm for 100 kHz. The EFs near the ossification front were 3.9 mV/cm for 1 kHz and EFs 21 mV/cm for 100 kHz (Figure 5D). On the other hand, the EFs intensity through the cartilage tend to be the same; for example, EFs of 0.2 mV/cm for 1 kHz were observed, while EFs of 7.9 mV/cm for 100 kHz were perceived (Figure 5E). The EFs were also measured in the cytoplasm of chondrocytes that were located in three different positions within the cartilage. The first measurement was performed in a chondrocyte located in the articular surface where the EFs were around 0.05 mV/cm for 1 kHz and 3.1 mV/cm for 100 kHz (Figure 5F). The second measurement was conducted in a chondrocyte located in the middle of the cartilage where the EFs were 0.08 mV/cm for 1 kHz and 3.4 mV/cm for 100 kHz (Figure 5G). Finally, the EFs were measured in a chondrocyte located near the ossification front. Here, the EFs were 0.03 mV/cm for 1 kHz and 0.3 mV/cm for 100 kHz; moreover, a negligible increase of the EFs inside the cytoplasm was observed (Figure 5H).", "bbox": [106, 457, 607, 699], "page_width": 1225, "page_height": 1582}, "marker_signature": {"type": "none", "raw_marker": null, "number": null, "kind": "generic_text", "normalized_text": "A heterogeneous EF distribution was observed inside the explant (Figure 5A). Results evidenced an increase of EFs in stimulated explants as the frequency was higher; in fact, the EFs inside the culture media were the same as reported in monolayer cultures with a negligible decrease of the EFs from the bottom to the upper surface (Figure 5B). The EFs were measured in both bone and cartilage of the explant (Figure 5C). On the one hand, different EF intensities along the bone were observed; for example, EFs of 8.3 mV/cm for 1 kHz and 573 mV/cm for 100 kHz were evidenced at the base of the bone. The EFs in the middle of the bone were 3 mV/cm for 1 kHz and 11.8 mV/cm for 100 kHz. The EFs near the ossification front were 3.9 mV/cm for 1 kHz and EFs 21 mV/cm for 100 kHz (Figure 5D). On the other hand, the EFs intensity through the cartilage tend to be the same; for example, EFs of 0.2 mV/cm for 1 kHz were observed, while EFs of 7.9 mV/cm for 100 kHz were perceived (Figure 5E). The EFs were also measured in the cytoplasm of chondrocytes that were located in three different positions within the cartilage. The first measurement was performed in a chondrocyte located in the articular surface where the EFs were around 0.05 mV/cm for 1 kHz and 3.1 mV/cm for 100 kHz (Figure 5F). The second measurement was conducted in a chondrocyte located in the middle of the cartilage where the EFs were 0.08 mV/cm for 1 kHz and 3.4 mV/cm for 100 kHz (Figure 5G). Finally, the EFs were measured in a chondrocyte located near the ossification front. Here, the EFs were 0.03 mV/cm for 1 kHz and 0.3 mV/cm for 100 kHz; moreover, a negligible increase of the EFs inside the cytoplasm was observed (Figure 5H)."}, "layout_signature": {"width": 501, "width_bucket": 500, "height": 242, "left": 106, "top": 457, "right": 607, "bottom": 699, "x_center": 356.5, "x_center_bucket": 350, "y_center": 578.0, "x_ratio": 0.291, "y_ratio": 0.3654, "width_ratio": 0.409, "height_ratio": 0.153, "line_count": 1}, "span_signature": {"font_size": 9.96, "font_size_median": 9.96, "font_size_bucket": 10.0, "font_family_norm": "CMR10", "bold": true, "italic": true, "span_count": 78}, "_in_visual_container": null, "_container_bbox": null, "_container_text": null, "_text_source": null, "_ocr_raw_status": null, "_ocr_raw_error_type": null, "render_default": true, "index_default": true, "zone": "body_zone", "style_family": "body_like", "style_family_authority": "body_family_anchor", "reading_band_id": "band_065", "display_cluster_candidate_id": "", "layout_region": 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J. VACA-GONZÁLEZ, J. F. ESCOBAR-HUERTAS AND D. A. GARZÓN-ALVARADO", "bbox": [590, 95, 1115, 113], "page_width": 1225, "page_height": 1582}, "marker_signature": {"type": "none", "raw_marker": null, "number": null, "kind": "generic_text", "normalized_text": "J. J. VACA-GONZÁLEZ, J. F. ESCOBAR-HUERTAS AND D. A. GARZÓN-ALVARADO"}, "layout_signature": {"width": 525, "width_bucket": 525, "height": 18, "left": 590, "top": 95, "right": 1115, "bottom": 113, "x_center": 852.5, "x_center_bucket": 850, "y_center": 104.0, "x_ratio": 0.6959, "y_ratio": 0.0657, "width_ratio": 0.4286, "height_ratio": 0.0114, "line_count": 1}, "span_signature": {"font_size": 6.97, "font_size_median": 6.97, "font_size_bucket": 7.0, "font_family_norm": "CMCSC10", "bold": false, "italic": true, "span_count": 19}, "_in_visual_container": null, "_container_bbox": null, "_container_text": null, "_text_source": null, "_ocr_raw_status": null, "_ocr_raw_error_type": null, "render_default": false, "index_default": false, "zone": "", "style_family": "body_like", "style_family_authority": "body_zone_with_anchor", "reading_band_id": "band_066", "display_cluster_candidate_id": "", "layout_region": "body_flow", "boundary_before": "none", "boundary_after": "none", "bridge_eligible": false, "insert_score": {"score": 0.15, "decision": "body", "evidence": ["narrow_width"]}, "role_verification_status": "ACCEPT", "role_source": "non_structural_normalized_role", "role_evidence": ["pre-gate normalized non-structural role preserved"]} +{"paper_id": "24YKLTHQ", "page": 8, "block_id": 2, "raw_label": "paragraph_title", "raw_order": 1, "bbox": [109, 144, 415, 167], "text": "3.3. EFs distribution in scaffolds", "page_width": 1225, "page_height": 1582, "role": "subsection_heading", "role_confidence": 0.85, "evidence": ["paragraph_title label with numbering: 3.3. EFs distribution in scaffolds"], "seed_role": "subsection_heading", "seed_confidence": 0.85, "seed_evidence": ["paragraph_title label with numbering: 3.3. EFs distribution in scaffolds"], "span_metadata": [{"size": 9.962599754333496, "font": "CMSL10", "flags": 6, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 9.962599754333496, "font": "CMSL10", "flags": 6, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 9.962599754333496, "font": "CMSL10", "flags": 6, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 9.962599754333496, "font": "CMSL10", "flags": 6, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 9.962599754333496, "font": "CMSL10", "flags": 6, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 9.962599754333496, "font": "CMSL10", "flags": 6, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 9.962599754333496, "font": "CMSL10", "flags": 6, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 9.962599754333496, "font": "CMSL10", "flags": 6, "color": 0, "dir": [1.0, 0.0], "wmode": 0}], "raw_observation": {"block_id": 2, "page": 8, "raw_label": "paragraph_title", "text": "3.3. EFs distribution in scaffolds", "bbox": [109, 144, 415, 167], "page_width": 1225, "page_height": 1582}, "marker_signature": {"type": "heading_numbered", "raw_marker": "3.3", "number": "3.3", "kind": "heading", "normalized_text": "3.3. EFs distribution in scaffolds"}, "layout_signature": {"width": 306, "width_bucket": 300, "height": 23, "left": 109, "top": 144, "right": 415, "bottom": 167, "x_center": 262.0, "x_center_bucket": 250, "y_center": 155.5, "x_ratio": 0.2139, "y_ratio": 0.0983, "width_ratio": 0.2498, "height_ratio": 0.0145, "line_count": 1}, "span_signature": {"font_size": 9.96, "font_size_median": 9.96, "font_size_bucket": 10.0, "font_family_norm": "CMSL10", "bold": false, "italic": true, "span_count": 8}, "_in_visual_container": null, "_container_bbox": null, "_container_text": null, "_text_source": null, "_ocr_raw_status": null, "_ocr_raw_error_type": null, "render_default": true, "index_default": true, "zone": "body_zone", "style_family": "heading_like", "style_family_authority": "heading_typography", "reading_band_id": "band_064", "display_cluster_candidate_id": "", "layout_region": "reference_candidate", "boundary_before": "weak", "boundary_after": "none", "bridge_eligible": false, "insert_score": {"score": 0.15, "decision": "body", "evidence": ["narrow_width"]}, "role_verification_status": "ACCEPT", "role_source": "accepted_heading", "role_evidence": ["heading verified by heading artifact"]} +{"paper_id": "24YKLTHQ", "page": 8, "block_id": 3, "raw_label": "text", "raw_order": 2, "bbox": [106, 186, 607, 429], "text": "A homogeneous EF flow distribution was evidenced inside the chondrogenic scaffold (Figure 6A). Results evidenced that the EFs tend to increase as the frequency was higher. For instance, the EFs in the culture media at 1 kHz were around 2.4 mV/cm, while EFs at 100 kHz were around 12.8 mV/cm (Figure 6B). Regarding the EFs within the hydrogel, it was observed that the EFs at 1 kHz were approximately 1.3 mV/cm, while the EFs at 100 kHz were around 16.7 mV/cm (Figure 6C). Here, it was possible to observe a slight decrease in the EFs within the hydrogel when frequencies of 10 Hz and 1 GHz were applied. The EFs were also measured in the cytoplasm of chondrocytes located in three different positions of the scaffold. The EFs in chondrocytes located at the upper surface of the scaffold were 0.07 mV/cm for 1 kHz and 3.2 mV/cm for 100 kHz (Figure 6D). The EFs in a chondrocyte located in the middle of the scaffold varied from 0.06 mV/cm for 1 kHz to 3.6 mV/cm for 100 kHz (Figure 6E). Finally, the EFs in a chondrocyte located at the bottom of the scaffold were 0.04 mV/cm for 1 kHz and 3.6 mV/cm for 100 kHz (Figure 6F).", "page_width": 1225, "page_height": 1582, "role": "body_paragraph", "role_confidence": 0.6, "evidence": ["default body_paragraph for text label"], "seed_role": "body_paragraph", "seed_confidence": 0.6, "seed_evidence": ["default body_paragraph for text label"], "span_metadata": [{"size": 9.962599754333496, "font": "CMR10", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 9.962599754333496, "font": "CMR10", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 9.962599754333496, "font": "CMR10", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 9.962599754333496, "font": "CMR10", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 9.962599754333496, "font": "CMR10", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 9.962599754333496, "font": "CMR10", "flags": 4, "color": 0, "dir": 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Results evidenced that the EFs tend to increase as the frequency was higher. For instance, the EFs in the culture media at 1 kHz were around 2.4 mV/cm, while EFs at 100 kHz were around 12.8 mV/cm (Figure 6B). Regarding the EFs within the hydrogel, it was observed that the EFs at 1 kHz were approximately 1.3 mV/cm, while the EFs at 100 kHz were around 16.7 mV/cm (Figure 6C). Here, it was possible to observe a slight decrease in the EFs within the hydrogel when frequencies of 10 Hz and 1 GHz were applied. The EFs were also measured in the cytoplasm of chondrocytes located in three different positions of the scaffold. The EFs in chondrocytes located at the upper surface of the scaffold were 0.07 mV/cm for 1 kHz and 3.2 mV/cm for 100 kHz (Figure 6D). The EFs in a chondrocyte located in the middle of the scaffold varied from 0.06 mV/cm for 1 kHz to 3.6 mV/cm for 100 kHz (Figure 6E). Finally, the EFs in a chondrocyte located at the bottom of the scaffold were 0.04 mV/cm for 1 kHz and 3.6 mV/cm for 100 kHz (Figure 6F).", "bbox": [106, 186, 607, 429], "page_width": 1225, "page_height": 1582}, "marker_signature": {"type": "none", "raw_marker": null, "number": null, "kind": "generic_text", "normalized_text": "A homogeneous EF flow distribution was evidenced inside the chondrogenic scaffold (Figure 6A). Results evidenced that the EFs tend to increase as the frequency was higher. For instance, the EFs in the culture media at 1 kHz were around 2.4 mV/cm, while EFs at 100 kHz were around 12.8 mV/cm (Figure 6B). Regarding the EFs within the hydrogel, it was observed that the EFs at 1 kHz were approximately 1.3 mV/cm, while the EFs at 100 kHz were around 16.7 mV/cm (Figure 6C). Here, it was possible to observe a slight decrease in the EFs within the hydrogel when frequencies of 10 Hz and 1 GHz were applied. The EFs were also measured in the cytoplasm of chondrocytes located in three different positions of the scaffold. The EFs in chondrocytes located at the upper surface of the scaffold were 0.07 mV/cm for 1 kHz and 3.2 mV/cm for 100 kHz (Figure 6D). The EFs in a chondrocyte located in the middle of the scaffold varied from 0.06 mV/cm for 1 kHz to 3.6 mV/cm for 100 kHz (Figure 6E). Finally, the EFs in a chondrocyte located at the bottom of the scaffold were 0.04 mV/cm for 1 kHz and 3.6 mV/cm for 100 kHz (Figure 6F)."}, "layout_signature": {"width": 501, "width_bucket": 500, "height": 243, "left": 106, "top": 186, "right": 607, "bottom": 429, "x_center": 356.5, "x_center_bucket": 350, "y_center": 307.5, "x_ratio": 0.291, "y_ratio": 0.1944, "width_ratio": 0.409, "height_ratio": 0.1536, "line_count": 1}, "span_signature": {"font_size": 9.96, "font_size_median": 9.96, "font_size_bucket": 10.0, "font_family_norm": "CMR10", "bold": true, "italic": true, "span_count": 161}, "_in_visual_container": null, "_container_bbox": null, "_container_text": null, "_text_source": null, "_ocr_raw_status": null, "_ocr_raw_error_type": null, "render_default": true, "index_default": true, "zone": "body_zone", "style_family": "body_like", "style_family_authority": "body_family_anchor", "reading_band_id": "band_064", "display_cluster_candidate_id": "", "layout_region": 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The findings demonstrated that depending on the frequencies applied, the chondrocytes experienced several EF concentrations at intra and extracellular level in the three settings computed. For instance, the EFs perceived by the cytoplasm were smaller compared to the EFs sensed by the extracellular environment. This electrical behavior is controlled by both the dielectric properties of the biological materials and the insulating properties of the plasma membrane. Although literature reports evidence that the EFs increase as the $ \\sigma $ is higher, the opposite effect was observed in this study, where a higher $ \\sigma $ of the cytoplasm reduces the magnitude of the induced EF that flows through it. Similar results were observed by Taghian et al., who evidenced that an increase in cytoplasm conductivity leads to lower EFs in the cytoplasm and higher EFs in the plasma membrane [30]. This particular behavior is also explained by the $ \\epsilon $ of the cytoplasm, since these dielectric constant decreases because the cytoplasm is polarized and overrides the internal EF. On the other hand, it has been described that the insulating effect of the cell membrane decreases as the frequency increases. For instance, cells are totally isolated by the plasma membrane when low frequencies are applied; therefore, the current is not able to penetrate the cell. Nevertheless, the insulating effect of the plasma membrane decreases as the frequency increases; thus, small current magnitudes are able to flow through the cell. Accordingly, when the plasma membrane is subjected to high frequencies, it behaves like a short-circuit and the current flows throughout the membrane by reaching the cytoplasm [36]. In this context, it is possible to mention that the plasma membrane acts as a capacitor, since the current that flows through a capacitor tends to increase as the frequency is higher.", "page_width": 1225, "page_height": 1582, "role": "body_paragraph", "role_confidence": 0.6, "evidence": ["default body_paragraph for text label"], "seed_role": "body_paragraph", "seed_confidence": 0.6, "seed_evidence": ["default body_paragraph for text label"], "span_metadata": [{"size": 9.962599754333496, "font": "CMR10", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 9.962599754333496, "font": "CMR10", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 9.962599754333496, "font": "CMR10", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 9.962599754333496, "font": "CMR10", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 9.962599754333496, "font": "CMR10", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 9.962599754333496, 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"wmode": 0}], "raw_observation": {"block_id": 3, "page": 9, "raw_label": "text", "text": "This study presents a computational model that evidences the effects generated by EFs on chondrocytes cultured in three different scenarios: monolayer culture, cartilage explant and chondrogenic scaffold. The findings demonstrated that depending on the frequencies applied, the chondrocytes experienced several EF concentrations at intra and extracellular level in the three settings computed. For instance, the EFs perceived by the cytoplasm were smaller compared to the EFs sensed by the extracellular environment. This electrical behavior is controlled by both the dielectric properties of the biological materials and the insulating properties of the plasma membrane. Although literature reports evidence that the EFs increase as the $ \\sigma $ is higher, the opposite effect was observed in this study, where a higher $ \\sigma $ of the cytoplasm reduces the magnitude of the induced EF that flows through it. Similar results were observed by Taghian et al., who evidenced that an increase in cytoplasm conductivity leads to lower EFs in the cytoplasm and higher EFs in the plasma membrane [30]. This particular behavior is also explained by the $ \\epsilon $ of the cytoplasm, since these dielectric constant decreases because the cytoplasm is polarized and overrides the internal EF. On the other hand, it has been described that the insulating effect of the cell membrane decreases as the frequency increases. For instance, cells are totally isolated by the plasma membrane when low frequencies are applied; therefore, the current is not able to penetrate the cell. Nevertheless, the insulating effect of the plasma membrane decreases as the frequency increases; thus, small current magnitudes are able to flow through the cell. Accordingly, when the plasma membrane is subjected to high frequencies, it behaves like a short-circuit and the current flows throughout the membrane by reaching the cytoplasm [36]. In this context, it is possible to mention that the plasma membrane acts as a capacitor, since the current that flows through a capacitor tends to increase as the frequency is higher.", "bbox": [106, 198, 608, 1133], "page_width": 1225, "page_height": 1582}, "marker_signature": {"type": "none", "raw_marker": null, "number": null, "kind": "generic_text", "normalized_text": "This study presents a computational model that evidences the effects generated by EFs on chondrocytes cultured in three different scenarios: monolayer culture, cartilage explant and chondrogenic scaffold. The findings demonstrated that depending on the frequencies applied, the chondrocytes experienced several EF concentrations at intra and extracellular level in the three settings computed. For instance, the EFs perceived by the cytoplasm were smaller compared to the EFs sensed by the extracellular environment. This electrical behavior is controlled by both the dielectric properties of the biological materials and the insulating properties of the plasma membrane. Although literature reports evidence that the EFs increase as the $ \\sigma $ is higher, the opposite effect was observed in this study, where a higher $ \\sigma $ of the cytoplasm reduces the magnitude of the induced EF that flows through it. Similar results were observed by Taghian et al., who evidenced that an increase in cytoplasm conductivity leads to lower EFs in the cytoplasm and higher EFs in the plasma membrane [30]. This particular behavior is also explained by the $ \\epsilon $ of the cytoplasm, since these dielectric constant decreases because the cytoplasm is polarized and overrides the internal EF. On the other hand, it has been described that the insulating effect of the cell membrane decreases as the frequency increases. For instance, cells are totally isolated by the plasma membrane when low frequencies are applied; therefore, the current is not able to penetrate the cell. Nevertheless, the insulating effect of the plasma membrane decreases as the frequency increases; thus, small current magnitudes are able to flow through the cell. Accordingly, when the plasma membrane is subjected to high frequencies, it behaves like a short-circuit and the current flows throughout the membrane by reaching the cytoplasm [36]. In this context, it is possible to mention that the plasma membrane acts as a capacitor, since the current that flows through a capacitor tends to increase as the frequency is higher."}, "layout_signature": {"width": 502, "width_bucket": 500, "height": 935, "left": 106, "top": 198, "right": 608, "bottom": 1133, "x_center": 357.0, "x_center_bucket": 350, "y_center": 665.5, "x_ratio": 0.2914, "y_ratio": 0.4207, "width_ratio": 0.4098, "height_ratio": 0.591, "line_count": 1}, "span_signature": {"font_size": 9.96, "font_size_median": 9.96, "font_size_bucket": 10.0, "font_family_norm": "CMR10", "bold": false, "italic": true, "span_count": 568}, "_in_visual_container": null, "_container_bbox": null, "_container_text": null, "_text_source": null, "_ocr_raw_status": null, "_ocr_raw_error_type": null, "render_default": true, "index_default": true, "zone": "body_zone", "style_family": "body_like", "style_family_authority": "body_family_anchor", "reading_band_id": "band_064", "display_cluster_candidate_id": "", "layout_region": "reference_candidate", "boundary_before": "weak", "boundary_after": "none", "bridge_eligible": false, "insert_score": {"score": 0.15, "decision": "body", "evidence": ["narrow_width"]}, "role_verification_status": "ACCEPT", "role_source": "non_structural_normalized_role", "role_evidence": ["pre-gate normalized non-structural role preserved"]} +{"paper_id": "24YKLTHQ", "page": 9, "block_id": 4, "raw_label": "text", "raw_order": 3, "bbox": [106, 1159, 607, 1449], "text": "Considering the cell membrane as a capacitor, the EF's in this computational model were applied in alternating current (AC). Furthermore, the model considered a variation of the frequencies, because a capacitor submitted to an AC with different frequencies is being constantly charged and discharged. In this sense, the plasma membrane is alternately charged and discharged at a rate determined by the frequency of the supply. This phenomenon is related with the activation of the plasma membrane ionic channels, as the application of external alternating EF's modifies the opening and closing of the Na⁺, Ka⁺ and Ca⁺ channels [37–39].\n\nEven though the activation of ionic channels of chondrocytes was not modelled, there are reports that have demonstrated that the voltage-dependent calcium channels (VDCC) are responsible to trigger different signaling pathways, which are involved in cell dynamics and molecular synthesis [40]. According to our results, this computational model is a useful tool that can predict both the EF intensity and frequency required to modify the influx and outflux of ions which may enhance the cell dynamics of chondrocytes. Although the EF's within the chondrocytes were similar in the monolayer culture, the cartilage explant and the scaffold, the extracellular EF's near the cell membrane varied considerably from each culture system to the others. This means that depending on the systems where the chondrocytes are cultured, specific stimulation schemes need to be applied to cells to trigger different cellular responses such as molecular gradient concentrations, proliferation, migration, among others [41]. For this reason, the computational model presented here is a promising tool that can be used to estimate the required EF's to overcome the chondrocyte membrane potential and modify the ionic gradient concentrations responsible for activating the signaling pathways of the chondrocytes.", "page_width": 1225, "page_height": 1582, "role": "body_paragraph", "role_confidence": 0.6, "evidence": ["default body_paragraph for text label"], "seed_role": "body_paragraph", "seed_confidence": 0.6, "seed_evidence": ["default body_paragraph for text label"], "span_metadata": [{"size": 9.962599754333496, "font": "CMR10", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 9.962599754333496, "font": "CMR10", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 9.962599754333496, "font": "CMR10", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 9.962599754333496, "font": "CMR10", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 9.962599754333496, 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"CMR10", "flags": 4, "color": 65280, "dir": [1.0, 0.0], "wmode": 0}, {"size": 9.962599754333496, "font": "CMR10", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 9.962599754333496, "font": "CMR10", "flags": 4, "color": 65280, "dir": [1.0, 0.0], "wmode": 0}, {"size": 9.962599754333496, "font": "CMR10", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}], "raw_observation": {"block_id": 4, "page": 9, "raw_label": "text", "text": "Considering the cell membrane as a capacitor, the EF's in this computational model were applied in alternating current (AC). Furthermore, the model considered a variation of the frequencies, because a capacitor submitted to an AC with different frequencies is being constantly charged and discharged. In this sense, the plasma membrane is alternately charged and discharged at a rate determined by the frequency of the supply. This phenomenon is related with the activation of the plasma membrane ionic channels, as the application of external alternating EF's modifies the opening and closing of the Na⁺, Ka⁺ and Ca⁺ channels [37–39].\n\nEven though the activation of ionic channels of chondrocytes was not modelled, there are reports that have demonstrated that the voltage-dependent calcium channels (VDCC) are responsible to trigger different signaling pathways, which are involved in cell dynamics and molecular synthesis [40]. According to our results, this computational model is a useful tool that can predict both the EF intensity and frequency required to modify the influx and outflux of ions which may enhance the cell dynamics of chondrocytes. Although the EF's within the chondrocytes were similar in the monolayer culture, the cartilage explant and the scaffold, the extracellular EF's near the cell membrane varied considerably from each culture system to the others. This means that depending on the systems where the chondrocytes are cultured, specific stimulation schemes need to be applied to cells to trigger different cellular responses such as molecular gradient concentrations, proliferation, migration, among others [41]. For this reason, the computational model presented here is a promising tool that can be used to estimate the required EF's to overcome the chondrocyte membrane potential and modify the ionic gradient concentrations responsible for activating the signaling pathways of the chondrocytes.", "bbox": [106, 1159, 607, 1449], "page_width": 1225, "page_height": 1582}, "marker_signature": {"type": "none", "raw_marker": null, "number": null, "kind": "generic_text", "normalized_text": "Considering the cell membrane as a capacitor, the EF's in this computational model were applied in alternating current (AC). Furthermore, the model considered a variation of the frequencies, because a capacitor submitted to an AC with different frequencies is being constantly charged and discharged. In this sense, the plasma membrane is alternately charged and discharged at a rate determined by the frequency of the supply. This phenomenon is related with the activation of the plasma membrane ionic channels, as the application of external alternating EF's modifies the opening and closing of the Na⁺, Ka⁺ and Ca⁺ channels [37–39].\n\nEven though the activation of ionic channels of chondrocytes was not modelled, there are reports that have demonstrated that the voltage-dependent calcium channels (VDCC) are responsible to trigger different signaling pathways, which are involved in cell dynamics and molecular synthesis [40]. According to our results, this computational model is a useful tool that can predict both the EF intensity and frequency required to modify the influx and outflux of ions which may enhance the cell dynamics of chondrocytes. Although the EF's within the chondrocytes were similar in the monolayer culture, the cartilage explant and the scaffold, the extracellular EF's near the cell membrane varied considerably from each culture system to the others. This means that depending on the systems where the chondrocytes are cultured, specific stimulation schemes need to be applied to cells to trigger different cellular responses such as molecular gradient concentrations, proliferation, migration, among others [41]. For this reason, the computational model presented here is a promising tool that can be used to estimate the required EF's to overcome the chondrocyte membrane potential and modify the ionic gradient concentrations responsible for activating the signaling pathways of the chondrocytes."}, "layout_signature": {"width": 501, "width_bucket": 500, "height": 290, "left": 106, "top": 1159, "right": 607, "bottom": 1449, "x_center": 356.5, "x_center_bucket": 350, "y_center": 1304.0, "x_ratio": 0.291, "y_ratio": 0.8243, "width_ratio": 0.409, "height_ratio": 0.1833, "line_count": 1}, "span_signature": {"font_size": 9.96, "font_size_median": 9.96, "font_size_bucket": 10.0, "font_family_norm": "CMR10", "bold": false, "italic": true, "span_count": 166}, "_in_visual_container": null, "_container_bbox": null, "_container_text": null, "_text_source": null, "_ocr_raw_status": null, "_ocr_raw_error_type": null, "render_default": true, "index_default": true, "zone": "body_zone", "style_family": 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"render_default": true, "index_default": true, "zone": "body_zone", "style_family": "body_like", "style_family_authority": "body_zone_with_anchor", "_needs_pdf_fallback": true, "reading_band_id": "band_063", "display_cluster_candidate_id": "", "layout_region": "body_flow", "boundary_before": "none", "boundary_after": "none", "bridge_eligible": false, "insert_score": {"score": 0.15, "decision": "body", "evidence": ["narrow_width"]}, "role_verification_status": "ACCEPT", "role_source": "non_structural_normalized_role", "role_evidence": ["pre-gate normalized non-structural role preserved"]} +{"paper_id": "24YKLTHQ", "page": 9, "block_id": 6, "raw_label": "text", "raw_order": 5, "bbox": [615, 778, 1118, 1424], "text": "Depending on the EFs applied and the stimulation time, the in vitro procedures of chondrocytes cultured in monolayer can be modified in order to increase cell proliferation and molecular synthesis. In fact, some experimental studies have evidenced that EFs in chondrocytes cultured in monolayer increase cell population and enhance the molecular synthesis of molecules such as glycosaminoglycans, collagen type II and aggrecan [14,15,23]. Accordingly, this computational model could be improved if the molecular events are modeled when external EFs are applied to the cells. Indeed, our most recent study evidences the role of EFs on the plasma membrane of single cells. This work demonstrated that depending on the intensity of the field and the frequency, it was possible to stimulate different cell membrane zones [42]. Combining these computational approaches, it is possible to establish the adequate parameters to stimulate cells, and accurately predict if the stimulation modifies the cell membrane potentials. A recent study simulated the EF distribution in a capacitive coupled system, in which a frequency of 60 kHz and an input voltage of 44.8 V were used to generate the EFs [43]. Although that computational model simulates a similar domain, the model did not consider the cell inside the culture well plate; for this reason, it was not possible to predict the EF around and inside the cell.", "page_width": 1225, "page_height": 1582, "role": "body_paragraph", "role_confidence": 0.6, "evidence": ["default body_paragraph for text label"], "seed_role": "body_paragraph", "seed_confidence": 0.6, "seed_evidence": ["default body_paragraph for text label"], "span_metadata": [{"size": 9.962599754333496, "font": "CMR10", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 9.962599754333496, "font": "CMR10", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 9.962599754333496, "font": "CMR10", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 9.962599754333496, "font": "CMR10", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 9.962599754333496, "font": "CMR10", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, 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In fact, some experimental studies have evidenced that EFs in chondrocytes cultured in monolayer increase cell population and enhance the molecular synthesis of molecules such as glycosaminoglycans, collagen type II and aggrecan [14,15,23]. Accordingly, this computational model could be improved if the molecular events are modeled when external EFs are applied to the cells. Indeed, our most recent study evidences the role of EFs on the plasma membrane of single cells. This work demonstrated that depending on the intensity of the field and the frequency, it was possible to stimulate different cell membrane zones [42]. Combining these computational approaches, it is possible to establish the adequate parameters to stimulate cells, and accurately predict if the stimulation modifies the cell membrane potentials. A recent study simulated the EF distribution in a capacitive coupled system, in which a frequency of 60 kHz and an input voltage of 44.8 V were used to generate the EFs [43]. Although that computational model simulates a similar domain, the model did not consider the cell inside the culture well plate; for this reason, it was not possible to predict the EF around and inside the cell.", "bbox": [615, 778, 1118, 1424], "page_width": 1225, "page_height": 1582}, "marker_signature": {"type": "none", "raw_marker": null, "number": null, "kind": "generic_text", "normalized_text": "Depending on the EFs applied and the stimulation time, the in vitro procedures of chondrocytes cultured in monolayer can be modified in order to increase cell proliferation and molecular synthesis. In fact, some experimental studies have evidenced that EFs in chondrocytes cultured in monolayer increase cell population and enhance the molecular synthesis of molecules such as glycosaminoglycans, collagen type II and aggrecan [14,15,23]. Accordingly, this computational model could be improved if the molecular events are modeled when external EFs are applied to the cells. Indeed, our most recent study evidences the role of EFs on the plasma membrane of single cells. This work demonstrated that depending on the intensity of the field and the frequency, it was possible to stimulate different cell membrane zones [42]. Combining these computational approaches, it is possible to establish the adequate parameters to stimulate cells, and accurately predict if the stimulation modifies the cell membrane potentials. A recent study simulated the EF distribution in a capacitive coupled system, in which a frequency of 60 kHz and an input voltage of 44.8 V were used to generate the EFs [43]. Although that computational model simulates a similar domain, the model did not consider the cell inside the culture well plate; for this reason, it was not possible to predict the EF around and inside the cell."}, "layout_signature": {"width": 503, "width_bucket": 500, "height": 646, "left": 615, "top": 778, "right": 1118, "bottom": 1424, "x_center": 866.5, "x_center_bucket": 875, "y_center": 1101.0, "x_ratio": 0.7073, "y_ratio": 0.696, "width_ratio": 0.4106, "height_ratio": 0.4083, "line_count": 1}, "span_signature": {"font_size": 9.96, "font_size_median": 9.96, "font_size_bucket": 10.0, "font_family_norm": "CMR10", "bold": false, "italic": true, "span_count": 405}, "_in_visual_container": null, "_container_bbox": null, "_container_text": null, "_text_source": null, "_ocr_raw_status": null, "_ocr_raw_error_type": null, "render_default": true, "index_default": true, "zone": "body_zone", "style_family": "body_like", "style_family_authority": "body_zone_with_anchor", "reading_band_id": 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J. VACA-GONZÁLEZ, J. F. ESCOBAR-HUERTAS AND D. A. GARZÓN-ALVARADO", "page_width": 1225, "page_height": 1582, "role": "noise", "role_confidence": 0.9, "evidence": ["header label"], "seed_role": "noise", "seed_confidence": 0.9, "seed_evidence": ["header label"], "span_metadata": [{"size": 6.973800182342529, "font": "CMCSC10", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 6.973800182342529, "font": "CMCSC10", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 6.973800182342529, "font": "CMCSC10", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 6.973800182342529, "font": "CMCSC10", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 6.973800182342529, "font": "CMCSC10", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 6.973800182342529, "font": "CMCSC10", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 6.973800182342529, "font": "CMCSC10", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 6.973800182342529, "font": "CMCSC10", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 6.973800182342529, "font": "CMCSC10", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 6.973800182342529, "font": "CMCSC10", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 6.973800182342529, "font": "CMCSC10", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 6.973800182342529, "font": "CMCSC10", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 6.973800182342529, "font": "CMCSC10", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 6.973800182342529, "font": "CMCSC10", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 6.973800182342529, "font": "CMCSC10", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 6.973800182342529, "font": "CMCSC10", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 6.973800182342529, "font": "CMCSC10", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 6.973800182342529, "font": "CMCSC10", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 6.973800182342529, "font": "CMCSC10", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}], "raw_observation": {"block_id": 1, "page": 10, "raw_label": "header", "text": "J. J. VACA-GONZÁLEZ, J. F. ESCOBAR-HUERTAS AND D. A. GARZÓN-ALVARADO", "bbox": [590, 95, 1115, 113], "page_width": 1225, "page_height": 1582}, "marker_signature": {"type": "none", "raw_marker": null, "number": null, "kind": "generic_text", "normalized_text": "J. J. VACA-GONZÁLEZ, J. F. ESCOBAR-HUERTAS AND D. A. 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In fact, the EFs tend to be similar within the chondrocytes regardless the location within the tissue. Experimental studies have demonstrated that electrical stimulation in cartilage explants stimulates the tissue growth and modifies the longitudinal position of the chondrocytes that are located near the ossification front $ [17] $. In a previous study, we evidenced that the EFs influence the columnar organization of chondrocytes located in the middle of a chondroepiphysis explant. Moreover, it was possible to identify that the EFs accelerate the hypertrophic process of chondrocytes located in the columnar zone of the chondroepiphysis $ [21] $. Although some studies have showed positive results in the application of EFs to cartilage explants, other works have evidenced that the electrical stimulation generates abnormal cartilage growth when the fields are not adequately applied $ [19] $. In this context, the appropriate intensity of the EFs applied is a relevant factor to consider, since the variation of voltages and frequencies can alter cartilage growth and keep the tissue in a quiescent state $ [11] $.", "page_width": 1225, "page_height": 1582, "role": "body_paragraph", "role_confidence": 0.6, "evidence": ["default body_paragraph for text label"], "seed_role": "body_paragraph", "seed_confidence": 0.6, "seed_evidence": ["default body_paragraph for text label"], "span_metadata": [{"size": 9.962599754333496, "font": "CMR10", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 9.962599754333496, "font": "CMR10", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 9.962599754333496, "font": "CMR10", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 9.962599754333496, "font": "CMR10", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 9.962599754333496, "font": "CMR10", "flags": 4, "color": 0, "dir": [1.0, 0.0], 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{"size": 9.962599754333496, "font": "CMR10", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 9.962599754333496, "font": "CMR10", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 9.962599754333496, "font": "CMR10", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 9.962599754333496, "font": "CMR10", "flags": 4, "color": 65280, "dir": [1.0, 0.0], "wmode": 0}, {"size": 9.962599754333496, "font": "CMR10", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}], "raw_observation": {"block_id": 2, "page": 10, "raw_label": "text", "text": "On the other hand, the EF intensities inside the cytoplasm of chondrocytes immersed in the native tissue were lower compared with the EFs in the extracellular matrix of the cartilage. In fact, the EFs tend to be similar within the chondrocytes regardless the location within the tissue. Experimental studies have demonstrated that electrical stimulation in cartilage explants stimulates the tissue growth and modifies the longitudinal position of the chondrocytes that are located near the ossification front $ [17] $. In a previous study, we evidenced that the EFs influence the columnar organization of chondrocytes located in the middle of a chondroepiphysis explant. Moreover, it was possible to identify that the EFs accelerate the hypertrophic process of chondrocytes located in the columnar zone of the chondroepiphysis $ [21] $. Although some studies have showed positive results in the application of EFs to cartilage explants, other works have evidenced that the electrical stimulation generates abnormal cartilage growth when the fields are not adequately applied $ [19] $. In this context, the appropriate intensity of the EFs applied is a relevant factor to consider, since the variation of voltages and frequencies can alter cartilage growth and keep the tissue in a quiescent state $ [11] $.", "bbox": [106, 145, 606, 720], "page_width": 1225, "page_height": 1582}, "marker_signature": {"type": "none", "raw_marker": null, "number": null, "kind": "generic_text", "normalized_text": "On the other hand, the EF intensities inside the cytoplasm of chondrocytes immersed in the native tissue were lower compared with the EFs in the extracellular matrix of the cartilage. In fact, the EFs tend to be similar within the chondrocytes regardless the location within the tissue. Experimental studies have demonstrated that electrical stimulation in cartilage explants stimulates the tissue growth and modifies the longitudinal position of the chondrocytes that are located near the ossification front $ [17] $. In a previous study, we evidenced that the EFs influence the columnar organization of chondrocytes located in the middle of a chondroepiphysis explant. Moreover, it was possible to identify that the EFs accelerate the hypertrophic process of chondrocytes located in the columnar zone of the chondroepiphysis $ [21] $. Although some studies have showed positive results in the application of EFs to cartilage explants, other works have evidenced that the electrical stimulation generates abnormal cartilage growth when the fields are not adequately applied $ [19] $. In this context, the appropriate intensity of the EFs applied is a relevant factor to consider, since the variation of voltages and frequencies can alter cartilage growth and keep the tissue in a quiescent state $ [11] $."}, "layout_signature": {"width": 500, "width_bucket": 500, "height": 575, "left": 106, "top": 145, "right": 606, "bottom": 720, "x_center": 356.0, "x_center_bucket": 350, "y_center": 432.5, "x_ratio": 0.2906, "y_ratio": 0.2734, "width_ratio": 0.4082, "height_ratio": 0.3635, "line_count": 1}, "span_signature": {"font_size": 9.96, "font_size_median": 9.96, "font_size_bucket": 10.0, "font_family_norm": "CMR10", "bold": false, "italic": true, "span_count": 286}, "_in_visual_container": null, "_container_bbox": null, "_container_text": null, "_text_source": null, "_ocr_raw_status": null, "_ocr_raw_error_type": null, "render_default": true, "index_default": true, "zone": "body_zone", "style_family": "body_like", "style_family_authority": "body_family_anchor", "reading_band_id": "band_064", "display_cluster_candidate_id": "", "layout_region": "reference_candidate", "boundary_before": "weak", "boundary_after": "none", "bridge_eligible": false, "insert_score": {"score": 0.15, "decision": "body", "evidence": ["narrow_width"]}, "role_verification_status": "ACCEPT", "role_source": "non_structural_normalized_role", "role_evidence": ["pre-gate normalized non-structural role preserved"]} +{"paper_id": "24YKLTHQ", "page": 10, "block_id": 3, "raw_label": "text", "raw_order": 2, "bbox": [107, 744, 607, 1272], "text": "Finally, the electrical stimulation on chondrogenic scaffolds evidenced that the distribution of EFs tends to be higher in an extracellular environment compared with the EFs perceived by the cytoplasm of chondrocytes. A study simulated the EF distribution in bioresorbable collagen type I scaffolds; however, the computational model considered just one frequency of 1 kHz and a voltage of 0.7 Vrms [44]. Moreover, that model did not consider the chondrocytes inside the scaffold. The computational model presented in this study provides a better understanding in how the EFs can distribute not only inside the three-dimensional construct but also inside the cytoplasm of chondrocytes. From an experimental point of view, the EFs have also been applied to tree-dimensional constructs. For instance, two studies evidenced opposite outcomes regarding cell proliferation and molecular synthesis in chondrocytes cultured in agarose systems and then electrically stimulated [20, 45]. Accordingly, this computational approach could be a promising tool that could estimate the EFs responsible to stimulate the chondrocytes and enhance their dynamics.", "page_width": 1225, "page_height": 1582, "role": "body_paragraph", "role_confidence": 0.6, "evidence": ["default body_paragraph for text label"], "seed_role": "body_paragraph", "seed_confidence": 0.6, "seed_evidence": ["default body_paragraph for text label"], "span_metadata": [{"size": 9.962599754333496, "font": "CMR10", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 9.962599754333496, "font": "CMR10", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 9.962599754333496, "font": "CMR10", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 9.962599754333496, "font": "CMR10", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 9.962599754333496, "font": "CMR10", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 9.962599754333496, "font": "CMR10", 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0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 9.962599754333496, "font": "CMR10", "flags": 4, "color": 0, "dir": [1.0, 0.0], "wmode": 0}], "raw_observation": {"block_id": 3, "page": 10, "raw_label": "text", "text": "Finally, the electrical stimulation on chondrogenic scaffolds evidenced that the distribution of EFs tends to be higher in an extracellular environment compared with the EFs perceived by the cytoplasm of chondrocytes. A study simulated the EF distribution in bioresorbable collagen type I scaffolds; however, the computational model considered just one frequency of 1 kHz and a voltage of 0.7 Vrms [44]. Moreover, that model did not consider the chondrocytes inside the scaffold. The computational model presented in this study provides a better understanding in how the EFs can distribute not only inside the three-dimensional construct but also inside the cytoplasm of chondrocytes. From an experimental point of view, the EFs have also been applied to tree-dimensional constructs. For instance, two studies evidenced opposite outcomes regarding cell proliferation and molecular synthesis in chondrocytes cultured in agarose systems and then electrically stimulated [20, 45]. Accordingly, this computational approach could be a promising tool that could estimate the EFs responsible to stimulate the chondrocytes and enhance their dynamics.", "bbox": [107, 744, 607, 1272], "page_width": 1225, "page_height": 1582}, "marker_signature": {"type": "none", "raw_marker": null, "number": null, "kind": "generic_text", "normalized_text": "Finally, the electrical stimulation on chondrogenic scaffolds evidenced that the distribution of EFs tends to be higher in an extracellular environment compared with the EFs perceived by the cytoplasm of chondrocytes. A study simulated the EF distribution in bioresorbable collagen type I scaffolds; however, the computational model considered just one frequency of 1 kHz and a voltage of 0.7 Vrms [44]. Moreover, that model did not consider the chondrocytes inside the scaffold. The computational model presented in this study provides a better understanding in how the EFs can distribute not only inside the three-dimensional construct but also inside the cytoplasm of chondrocytes. From an experimental point of view, the EFs have also been applied to tree-dimensional constructs. For instance, two studies evidenced opposite outcomes regarding cell proliferation and molecular synthesis in chondrocytes cultured in agarose systems and then electrically stimulated [20, 45]. Accordingly, this computational approach could be a promising tool that could estimate the EFs responsible to stimulate the chondrocytes and enhance their dynamics."}, "layout_signature": {"width": 500, "width_bucket": 500, "height": 528, "left": 107, "top": 744, "right": 607, "bottom": 1272, "x_center": 357.0, "x_center_bucket": 350, "y_center": 1008.0, "x_ratio": 0.2914, "y_ratio": 0.6372, "width_ratio": 0.4082, "height_ratio": 0.3338, "line_count": 1}, "span_signature": {"font_size": 9.96, "font_size_median": 9.96, "font_size_bucket": 10.0, "font_family_norm": "CMR10", "bold": false, "italic": true, "span_count": 293}, "_in_visual_container": null, "_container_bbox": null, "_container_text": null, "_text_source": null, "_ocr_raw_status": null, "_ocr_raw_error_type": null, "render_default": true, "index_default": true, "zone": "body_zone", "style_family": "body_like", "style_family_authority": "body_family_anchor", "reading_band_id": "band_064", "display_cluster_candidate_id": "", "layout_region": "reference_candidate", "boundary_before": "weak", "boundary_after": "none", "bridge_eligible": false, "insert_score": {"score": 0.15, "decision": "body", "evidence": ["narrow_width"]}, "role_verification_status": "ACCEPT", "role_source": "non_structural_normalized_role", "role_evidence": ["pre-gate normalized non-structural role preserved"]} +{"paper_id": "24YKLTHQ", "page": 10, "block_id": 4, "raw_label": "paragraph_title", "raw_order": 3, "bbox": [109, 1306, 277, 1328], "text": "5. Conclusions", "page_width": 1225, "page_height": 1582, "role": "section_heading", "role_confidence": 0.85, "evidence": ["paragraph_title label with numbering: 5. Conclusions"], "seed_role": "section_heading", "seed_confidence": 0.85, "seed_evidence": ["paragraph_title label with numbering: 5. Conclusions"], "span_metadata": [{"size": 9.962599754333496, "font": "CMBX10", "flags": 20, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 9.962599754333496, "font": "CMBX10", "flags": 20, "color": 0, "dir": [1.0, 0.0], "wmode": 0}], "raw_observation": {"block_id": 4, "page": 10, "raw_label": "paragraph_title", "text": "5. Conclusions", "bbox": [109, 1306, 277, 1328], "page_width": 1225, "page_height": 1582}, "marker_signature": {"type": "heading_numbered", "raw_marker": "5", "number": "5", "kind": "heading", "normalized_text": "5. Conclusions"}, "layout_signature": {"width": 168, "width_bucket": 175, "height": 22, "left": 109, "top": 1306, "right": 277, "bottom": 1328, "x_center": 193.0, "x_center_bucket": 200, "y_center": 1317.0, "x_ratio": 0.1576, "y_ratio": 0.8325, "width_ratio": 0.1371, "height_ratio": 0.0139, "line_count": 1}, "span_signature": {"font_size": 9.96, "font_size_median": 9.96, "font_size_bucket": 10.0, "font_family_norm": "CMBX10", "bold": true, "italic": true, "span_count": 2}, "_in_visual_container": null, "_container_bbox": null, "_container_text": null, "_text_source": null, "_ocr_raw_status": null, "_ocr_raw_error_type": null, "render_default": true, "index_default": true, "zone": "body_zone", "style_family": "heading_like", "style_family_authority": "heading_typography", "reading_band_id": "band_065", "display_cluster_candidate_id": "", "layout_region": "reference_candidate", "boundary_before": "weak", "boundary_after": "none", "bridge_eligible": false, "insert_score": {"score": 0.15, "decision": "body", "evidence": ["narrow_width"]}, "role_verification_status": "ACCEPT", "role_source": "accepted_heading", "role_evidence": ["heading verified by heading artifact"]} +{"paper_id": "24YKLTHQ", "page": 10, "block_id": 5, "raw_label": "text", "raw_order": 4, "bbox": [106, 1351, 605, 1447], "text": "Overall, electrical stimulation has proven to influence the cell dynamics in chondrocytes within a monolayer culture, a cartilage explant and a chondrogenic three-dimensional construct. This control is achieved by combining the appropriate input parameters, such as frequency and voltage. A suitable combination of these factors can provide the desired results, such as the increase in cell population, morphological changes of chondrocytes and stimulation of characteristic cartilage tissue molecules. Given the results obtained in relation to the frequency dependence of the effects of EFs in chondrocytes, a new field of research may be opened to study how a biophysical stimulus could improve the therapeutic outcomes of chondrocytes, cartilage explants and 3D constructs used to regenerate injured tissues. In addition, this computational approach is a novel and potential tool that can be used to create special bioreactors to generate distinct electrical intensities according to the necessity of a particular cartilage treatment. This study may contribute to tissue engineering because biophysical stimuli are the basis for the next generation of cartilage regeneration technology. 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Becerra, J. Andrades, E. Guerado, P. Zamora-Navas, J. Lopez-Puertas, and A. Reddi, \"Articular cartilage: structure and regeneration\", Tissue Eng Part B Rev, vol. 16, no. 6, pp. 617-627, 2010. https://doi.org/10.1089/ten.teb.2010.0191", "page_width": 1225, "page_height": 1582, "role": "reference_item", "role_confidence": 0.85, "evidence": ["reference content label: [4] J. Becerra, J. Andrades, E. Guerado, P. Zamora-Navas, J."], "seed_role": "reference_item", "seed_confidence": 0.85, "seed_evidence": ["reference content label: [4] J. Becerra, J. Andrades, E. Guerado, P. 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Mackie, L. Tatarzuch, and M. Mirams, \"The skeleton: a multi-functional complex organ: the growth plate chondrocyte and endochondral ossification\", J Endocrinol,", "bbox": [620, 1351, 1115, 1445], "page_width": 1225, "page_height": 1582}, "marker_signature": {"type": "reference_numeric_bracket", "raw_marker": "[5]", "number": 5, "kind": "reference", "normalized_text": "[5] E. Mackie, L. Tatarzuch, and M. 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Star, \"Capacitively coupled electrical stimulation of bovine growth plate chondrocytes grown in pellet form\", J Orthop Res, vol. 6, no. 2, pp. 265-271, 1988. https://doi.org/10.1002/jor.1100060214"}, "layout_signature": {"width": 493, "width_bucket": 500, "height": 119, "left": 112, "top": 606, "right": 605, "bottom": 725, "x_center": 358.5, "x_center_bucket": 350, "y_center": 665.5, "x_ratio": 0.2927, "y_ratio": 0.4207, "width_ratio": 0.4024, "height_ratio": 0.0752, "line_count": 1}, "span_signature": {"font_size": 9.96, "font_size_median": 9.96, "font_size_bucket": 10.0, "font_family_norm": "CMR10", "bold": false, "italic": true, "span_count": 37}, "_in_visual_container": null, "_container_bbox": null, "_container_text": null, "_text_source": null, "_ocr_raw_status": null, "_ocr_raw_error_type": null, "render_default": true, "index_default": true, "zone": "reference_zone", "style_family": "reference_like", "style_family_authority": "reference_marker", "reading_band_id": "band_060", "display_cluster_candidate_id": "", "layout_region": "reference_candidate", "boundary_before": "weak", "boundary_after": "none", "bridge_eligible": false, "insert_score": {"score": 0.15, "decision": "body", "evidence": ["narrow_width"]}, "role_verification_status": "ACCEPT", "role_source": "reference_zone_item", "role_evidence": ["reference item matched zone"]} +{"paper_id": "24YKLTHQ", "page": 11, "block_id": 7, "raw_label": "reference_content", "raw_order": 6, "bbox": [112, 746, 604, 888], "text": "[10] C. T. Brighton, L. Jensen, S. R. Pollack, B. S. Tolin, and C. C. Clark, “Proliferative and synthetic response of bovine growth plate chondrocytes to various capacitively coupled electrical fields”, J. Orthop. Res., https://doi.org/10.1002/jor.1100070519", "page_width": 1225, "page_height": 1582, "role": "reference_item", "role_confidence": 0.85, "evidence": ["reference content label: [10] C. T. Brighton, L. Jensen, S. R. Pollack, B. S. Tolin, "], "seed_role": "reference_item", "seed_confidence": 0.85, "seed_evidence": ["reference content label: [10] C. T. Brighton, L. Jensen, S. R. Pollack, B. S. 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T. Brighton, L. Jensen, S. R. Pollack, B. S. Tolin, and C. C. Clark, “Proliferative and synthetic response of bovine growth plate chondrocytes to various capacitively coupled electrical fields”, J. Orthop. Res., https://doi.org/10.1002/jor.1100070519", "bbox": [112, 746, 604, 888], "page_width": 1225, "page_height": 1582}, "marker_signature": {"type": "reference_numeric_bracket", "raw_marker": "[10]", "number": 10, "kind": "reference", "normalized_text": "[10] C. T. Brighton, L. Jensen, S. R. Pollack, B. S. Tolin, and C. C. Clark, “Proliferative and synthetic response of bovine growth plate chondrocytes to various capacitively coupled electrical fields”, J. Orthop. 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Brighton, G. Pfeffer, and S. Pollack, “In vivo growth plate stimulation in various capacitively coupled electrical fields”, J. Orthop. Res., vol. 1, no. 1, pp. 42-49, 1983. https://doi.org/10.1002/jor.1100010106", "page_width": 1225, "page_height": 1582, "role": "reference_item", "role_confidence": 0.85, "evidence": ["reference content label: [11] C. Brighton, G. Pfeffer, and S. Pollack, “In vivo growt"], "seed_role": "reference_item", "seed_confidence": 0.85, "seed_evidence": ["reference content label: [11] C. Brighton, G. Pfeffer, and S. 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Brighton, G. Pfeffer, and S. Pollack, “In vivo growth plate stimulation in various capacitively coupled electrical fields”, J. Orthop. Res., vol. 1, no. 1, pp. 42-49, 1983. https://doi.org/10.1002/jor.1100010106", "bbox": [113, 908, 603, 1026], "page_width": 1225, "page_height": 1582}, "marker_signature": {"type": "reference_numeric_bracket", "raw_marker": "[11]", "number": 11, "kind": "reference", "normalized_text": "[11] C. Brighton, G. Pfeffer, and S. Pollack, “In vivo growth plate stimulation in various capacitively coupled electrical fields”, J. Orthop. 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Brighton and P. Townsend, “Increased cAMP production after short-term capacitively coupled stimulation in bovine growth plate chondrocytes”, J Orthop Res, vol. 6, no. 4, pp. 552-558, 1988. https://doi.org/10.1002/jor.1100060412", "page_width": 1225, "page_height": 1582, "role": "reference_item", "role_confidence": 0.85, "evidence": ["reference content label: [12] C. Brighton and P. Townsend, “Increased cAMP production"], "seed_role": "reference_item", "seed_confidence": 0.85, "seed_evidence": ["reference content label: [12] C. Brighton and P. 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Brighton and P. Townsend, “Increased cAMP production after short-term capacitively coupled stimulation in bovine growth plate chondrocytes”, J Orthop Res, vol. 6, no. 4, pp. 552-558, 1988. https://doi.org/10.1002/jor.1100060412", "bbox": [113, 1049, 606, 1166], "page_width": 1225, "page_height": 1582}, "marker_signature": {"type": "reference_numeric_bracket", "raw_marker": "[12]", "number": 12, "kind": "reference", "normalized_text": "[12] C. Brighton and P. 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Brighton, A. Unger, and J. Stambough, “In vitro growth of bovine articular cartilage chondrocytes in various capacitively coupled electrical fields”, J Orthop Res, vol. 2, no. 1, pp. 15-22, 1984. https://doi.org/10.1002/jor.1100020104", "page_width": 1225, "page_height": 1582, "role": "reference_item", "role_confidence": 0.85, "evidence": ["reference content label: [13] C. Brighton, A. Unger, and J. Stambough, “In vitro grow"], "seed_role": "reference_item", "seed_confidence": 0.85, "seed_evidence": ["reference content label: [13] C. Brighton, A. Unger, and J. 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T. Brighton, G. B. Pfeffer, and S. R. Pollack, “In vivo growth plate stimulation in various capacitively coupled electrical fields”, J. Orthop. Res., vol. 1, no. 1, pp. 42-49, 1983. https://doi.org/10.1002/jor.1100010106", "bbox": [621, 287, 1114, 403], "page_width": 1225, "page_height": 1582}, "marker_signature": {"type": "reference_numeric_bracket", "raw_marker": "[16]", "number": 16, "kind": "reference", "normalized_text": "[16] C. T. Brighton, G. B. Pfeffer, and S. R. Pollack, “In vivo growth plate stimulation in various capacitively coupled electrical fields”, J. Orthop. 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Forgon, V. Vámhidy, and L. Kellényi, “Bone growth accelerated by stimulation of the epiphyseal plate with electric current”, Arch. Orthop. Trauma. Surg., vol. 104, no. 2, pp. 121-124, 1985. https://doi.org/10.1007/BF00454252", "page_width": 1225, "page_height": 1582, "role": "reference_item", "role_confidence": 0.85, "evidence": ["reference content label: [17] M. Forgon, V. Vámhidy, and L. Kellényi, “Bone growth ac"], "seed_role": "reference_item", "seed_confidence": 0.85, "seed_evidence": ["reference content label: [17] M. Forgon, V. Vámhidy, and L. 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J. Vaca-González, J. Escobar, J. Guevara, Y. Hata, G. Gallego Ferrer, and D. A. Garzón-Alvarado, \"Capacitively coupled electrical stimulation of rat chondroepiphysis explants: A histomorphometric analysis\", Bioelectrochemistry, vol. 126, pp. 1-11, 2019. https://doi.org/10.1016/j.bioelechem.2018.11.004", "bbox": [622, 924, 1114, 1089], "page_width": 1225, "page_height": 1582}, "marker_signature": {"type": "reference_numeric_bracket", "raw_marker": "[21]", "number": 21, "kind": "reference", "normalized_text": "[21] J. J. Vaca-González, J. Escobar, J. Guevara, Y. Hata, G. Gallego Ferrer, and D. A. 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J. Vaca-González, J. Guevara, J. Vega, and D. A. Garzón-Alvarado, \"An in vitro chondrocyte electrical stimulation framework: a methodology to calculate electric fields and modulate proliferation, cell death and glycosaminoglycan synthesis\", Cell. Mol. Bioeng., vol. 9, no. 1, pp. 116-126, 2016. https://doi.org/10.1007/s12195-015-0419-2", "page_width": 1225, "page_height": 1582, "role": "reference_item", "role_confidence": 0.85, "evidence": ["reference content label: [22] J. J. Vaca-González, J. Guevara, J. Vega, and D. A. Gar"], "seed_role": "reference_item", "seed_confidence": 0.85, "seed_evidence": ["reference content label: [22] J. J. Vaca-González, J. Guevara, J. Vega, and D. A. 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J. Vaca-González, J. Guevara, J. Vega, and D. A. Garzón-Alvarado, \"An in vitro chondrocyte electrical stimulation framework: a methodology to calculate electric fields and modulate proliferation, cell death and glycosaminoglycan synthesis\", Cell. Mol. Bioeng., vol. 9, no. 1, pp. 116-126, 2016. https://doi.org/10.1007/s12195-015-0419-2", "bbox": [621, 1114, 1115, 1280], "page_width": 1225, "page_height": 1582}, "marker_signature": {"type": "reference_numeric_bracket", "raw_marker": "[22]", "number": 22, "kind": "reference", "normalized_text": "[22] J. J. Vaca-González, J. Guevara, J. Vega, and D. A. Garzón-Alvarado, \"An in vitro chondrocyte electrical stimulation framework: a methodology to calculate electric fields and modulate proliferation, cell death and glycosaminoglycan synthesis\", Cell. Mol. 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Hung\nCellular Engineering Laboratory,\nDepartment of Biomedical Engineering,\nColumbia University,\nNew York, NY 10027\ne-mail: cth6@columbia.edu\nUsing a custom galvanotaxis chamber and time-lapse digital video microscopy, we report the novel observation that cultured chondrocytes exhibit cathodal migration when subjected to applied direct current (DC) electric fields as low as 0.8 V/cm. The response was dose-dependent for field strengths greater than 4 V/cm. Cell migration appeared to be an active process with extension of cytoplasmic processes in the direction of movement. In some cells, field application for greater than an hour induced elongation of initially round cells accompanied by perpendicular alignment of the long axis with respect to the applied field. Antagonists of the inositol phospholipid pathway, U-73122 and neomycin, were able to inhibit cathodal migration. Cell migration toward the cathode did not require the presence of serum during field application. 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Hung\nCellular Engineering Laboratory,\nDepartment of Biomedical Engineering,\nColumbia University,\nNew York, NY 10027\ne-mail: cth6@columbia.edu\nUsing a custom galvanotaxis chamber and time-lapse digital video microscopy, we report the novel observation that cultured chondrocytes exhibit cathodal migration when subjected to applied direct current (DC) electric fields as low as 0.8 V/cm. The response was dose-dependent for field strengths greater than 4 V/cm. Cell migration appeared to be an active process with extension of cytoplasmic processes in the direction of movement. In some cells, field application for greater than an hour induced elongation of initially round cells accompanied by perpendicular alignment of the long axis with respect to the applied field. Antagonists of the inositol phospholipid pathway, U-73122 and neomycin, were able to inhibit cathodal migration. Cell migration toward the cathode did not require the presence of serum during field application. 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Hung\nCellular Engineering Laboratory,\nDepartment of Biomedical Engineering,\nColumbia University,\nNew York, NY 10027\ne-mail: cth6@columbia.edu\nUsing a custom galvanotaxis chamber and time-lapse digital video microscopy, we report the novel observation that cultured chondrocytes exhibit cathodal migration when subjected to applied direct current (DC) electric fields as low as 0.8 V/cm. The response was dose-dependent for field strengths greater than 4 V/cm. Cell migration appeared to be an active process with extension of cytoplasmic processes in the direction of movement. In some cells, field application for greater than an hour induced elongation of initially round cells accompanied by perpendicular alignment of the long axis with respect to the applied field. Antagonists of the inositol phospholipid pathway, U-73122 and neomycin, were able to inhibit cathodal migration. Cell migration toward the cathode did not require the presence of serum during field application. 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Hung\nCellular Engineering Laboratory,\nDepartment of Biomedical Engineering,\nColumbia University,\nNew York, NY 10027\ne-mail: cth6@columbia.edu\nUsing a custom galvanotaxis chamber and time-lapse digital video microscopy, we report the novel observation that cultured chondrocytes exhibit cathodal migration when subjected to applied direct current (DC) electric fields as low as 0.8 V/cm. The response was dose-dependent for field strengths greater than 4 V/cm. Cell migration appeared to be an active process with extension of cytoplasmic processes in the direction of movement. In some cells, field application for greater than an hour induced elongation of initially round cells accompanied by perpendicular alignment of the long axis with respect to the applied field. Antagonists of the inositol phospholipid pathway, U-73122 and neomycin, were able to inhibit cathodal migration. Cell migration toward the cathode did not require the presence of serum during field application. 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very limited capacity to heal after injury [1]. There exists evidence in the literature suggesting that cell migration and invasion may play an important role in cartilage repair [1–3]. More specifically, repopulation of articular cartilage lesions in vivo implies that chondrocytes and/or precursor chondrocytes are capable of migration in situ [1]. Consistent with this concept, Reindel and co-workers have observed chondrocyte migration to the interface region of articular cartilage held in apposition in vitro [4]. Related to migration, chondrocyte adhesion has also been implicated in the successful repair of cartilage [5]. It is therefore conceivable that strategies designed to direct chondrocyte movement can be developed to enhance cartilage healing and repair as well as facilitate efforts for cartilage tissue engineering. The development and optimization such strategies will entail elucidation of the basic mechanisms underlying chondrocyte migration.", "page_width": 1224, "page_height": 1584, "role": "body_paragraph", "role_confidence": 0.6, "evidence": ["default body_paragraph for text label"], "seed_role": "body_paragraph", "seed_confidence": 0.6, "seed_evidence": ["default body_paragraph for text label"], "span_metadata": [{"size": 8.979999542236328, "font": "Times-Roman", "flags": 4, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 8.979999542236328, "font": "Times-Roman", "flags": 4, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 8.979999542236328, "font": "Times-Roman", "flags": 4, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 8.979999542236328, "font": "Times-Roman", "flags": 4, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 8.979999542236328, "font": "Universal-GreekwithMathP", "flags": 4, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 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There exists evidence in the literature suggesting that cell migration and invasion may play an important role in cartilage repair [1–3]. More specifically, repopulation of articular cartilage lesions in vivo implies that chondrocytes and/or precursor chondrocytes are capable of migration in situ [1]. Consistent with this concept, Reindel and co-workers have observed chondrocyte migration to the interface region of articular cartilage held in apposition in vitro [4]. Related to migration, chondrocyte adhesion has also been implicated in the successful repair of cartilage [5]. It is therefore conceivable that strategies designed to direct chondrocyte movement can be developed to enhance cartilage healing and repair as well as facilitate efforts for cartilage tissue engineering. The development and optimization such strategies will entail elucidation of the basic mechanisms underlying chondrocyte migration.", "bbox": [115, 738, 603, 1068], "page_width": 1224, "page_height": 1584}, "marker_signature": {"type": "none", "raw_marker": null, "number": null, "kind": "generic_text", "normalized_text": "Adult articular cartilage exhibits a very limited capacity to heal after injury [1]. There exists evidence in the literature suggesting that cell migration and invasion may play an important role in cartilage repair [1–3]. More specifically, repopulation of articular cartilage lesions in vivo implies that chondrocytes and/or precursor chondrocytes are capable of migration in situ [1]. Consistent with this concept, Reindel and co-workers have observed chondrocyte migration to the interface region of articular cartilage held in apposition in vitro [4]. Related to migration, chondrocyte adhesion has also been implicated in the successful repair of cartilage [5]. It is therefore conceivable that strategies designed to direct chondrocyte movement can be developed to enhance cartilage healing and repair as well as facilitate efforts for cartilage tissue engineering. The development and optimization such strategies will entail elucidation of the basic mechanisms underlying chondrocyte migration."}, "layout_signature": {"width": 488, "width_bucket": 500, "height": 330, "left": 115, "top": 738, "right": 603, "bottom": 1068, "x_center": 359.0, "x_center_bucket": 350, "y_center": 903.0, "x_ratio": 0.2933, "y_ratio": 0.5701, "width_ratio": 0.3987, "height_ratio": 0.2083, "line_count": 1}, "span_signature": {"font_size": 8.98, "font_size_median": 8.98, "font_size_bucket": 9.0, "font_family_norm": "Times-Roman", "bold": false, "italic": true, "span_count": 257}, "_in_visual_container": null, "_container_bbox": null, "_container_text": null, "_text_source": null, "_ocr_raw_status": null, "_ocr_raw_error_type": null, "render_default": true, "index_default": true, "zone": "body_zone", "style_family": "body_like", "style_family_authority": "body_zone_with_anchor", "reading_band_id": "band_039", "display_cluster_candidate_id": "", "layout_region": "reference_candidate", "boundary_before": "weak", "boundary_after": "none", "bridge_eligible": false, "insert_score": {"score": 0.15, "decision": "body", "evidence": ["narrow_width"]}, "role_verification_status": "ACCEPT", "role_source": "non_structural_normalized_role", "role_evidence": ["pre-gate normalized non-structural role preserved"]} +{"paper_id": "28JLIHLS", "page": 1, "block_id": 8, "raw_label": "text", "raw_order": 9, "bbox": [115, 1069, 604, 1377], "text": "Chemical and mechanical stimuli are known to cause directed movement in a number of different cell types (e.g. [3,6,7]). Less prominently studied, DC electric fields are known to induce a similar response. Galvanotaxis and galvanotropism (migration and shape change) in response to applied direct current (DC) electric fields, respectively, have been demonstrated in a number of cell types. For instance, field strengths of 1–10 V/cm have been reported to induce migration in keratinocytes, corneal epithelial cells, bone cells, and fibroblasts (e.g., [8–12]). The generation of the electric field necessary for a galvanotactic response is not isolated to externally applied fields under artificial conditions. It has been shown, for instance, that there exist electric field gradients in both healing wounds and developing embryos [13]. When any tissue is traumatized, injury potentials are created and steady electric fields exist locally for days after the insult. These potentials, which result largely from ion flux through leaky cell membranes, are basically direct current (DC)-like and decay with time. These electric fields are believed to be on the order of 1–2 V/cm at the cut surface of wounds [10]. Thus, the phenomenon of galvanotaxis may prove very useful in the understanding of embryonic development, wound healing, and in tissue engineering applications. To our knowledge, galvanotaxis in chondrocytes has not been previously demonstrated.", "page_width": 1224, "page_height": 1584, "role": "body_paragraph", "role_confidence": 0.6, "evidence": ["default body_paragraph for text label"], "seed_role": "body_paragraph", "seed_confidence": 0.6, "seed_evidence": ["default body_paragraph for text label"], "span_metadata": [{"size": 8.979999542236328, "font": "Times-Roman", "flags": 4, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 8.979999542236328, "font": "Times-Roman", "flags": 4, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 8.979999542236328, "font": "Times-Roman", "flags": 4, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 8.979999542236328, "font": "Times-Roman", "flags": 4, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 8.979999542236328, "font": "Times-Roman", "flags": 4, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 8.979999542236328, "font": "Times-Roman", "flags": 4, 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Less prominently studied, DC electric fields are known to induce a similar response. Galvanotaxis and galvanotropism (migration and shape change) in response to applied direct current (DC) electric fields, respectively, have been demonstrated in a number of cell types. For instance, field strengths of 1–10 V/cm have been reported to induce migration in keratinocytes, corneal epithelial cells, bone cells, and fibroblasts (e.g., [8–12]). The generation of the electric field necessary for a galvanotactic response is not isolated to externally applied fields under artificial conditions. It has been shown, for instance, that there exist electric field gradients in both healing wounds and developing embryos [13]. When any tissue is traumatized, injury potentials are created and steady electric fields exist locally for days after the insult. These potentials, which result largely from ion flux through leaky cell membranes, are basically direct current (DC)-like and decay with time. These electric fields are believed to be on the order of 1–2 V/cm at the cut surface of wounds [10]. Thus, the phenomenon of galvanotaxis may prove very useful in the understanding of embryonic development, wound healing, and in tissue engineering applications. To our knowledge, galvanotaxis in chondrocytes has not been previously demonstrated.", "bbox": [115, 1069, 604, 1377], "page_width": 1224, "page_height": 1584}, "marker_signature": {"type": "none", "raw_marker": null, "number": null, "kind": "generic_text", "normalized_text": "Chemical and mechanical stimuli are known to cause directed movement in a number of different cell types (e.g. [3,6,7]). Less prominently studied, DC electric fields are known to induce a similar response. Galvanotaxis and galvanotropism (migration and shape change) in response to applied direct current (DC) electric fields, respectively, have been demonstrated in a number of cell types. For instance, field strengths of 1–10 V/cm have been reported to induce migration in keratinocytes, corneal epithelial cells, bone cells, and fibroblasts (e.g., [8–12]). The generation of the electric field necessary for a galvanotactic response is not isolated to externally applied fields under artificial conditions. It has been shown, for instance, that there exist electric field gradients in both healing wounds and developing embryos [13]. When any tissue is traumatized, injury potentials are created and steady electric fields exist locally for days after the insult. These potentials, which result largely from ion flux through leaky cell membranes, are basically direct current (DC)-like and decay with time. These electric fields are believed to be on the order of 1–2 V/cm at the cut surface of wounds [10]. Thus, the phenomenon of galvanotaxis may prove very useful in the understanding of embryonic development, wound healing, and in tissue engineering applications. 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In their chemotaxis studies, chondrocyte movement was directed by a cytokine gradient of bone morphogenic protein (BMP). In a more recent study, cultured chondrocytes have been shown to migrate in response to gradients of extracellular matrix molecules using Boyden chambers [14]. In the present study, our objective was to examine basic science aspects of directed chondrocyte migration to applied electric field gradients using a novel galvanotaxis chamber and time-lapse digital video microscopy. Characterization of the response in addition to studies aimed at exploring mechanisms of migration were performed. 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demonstrate directed chondrocyte migration. In their chemotaxis studies, chondrocyte movement was directed by a cytokine gradient of bone morphogenic protein (BMP). In a more recent study, cultured chondrocytes have been shown to migrate in response to gradients of extracellular matrix molecules using Boyden chambers [14]. In the present study, our objective was to examine basic science aspects of directed chondrocyte migration to applied electric field gradients using a novel galvanotaxis chamber and time-lapse digital video microscopy. Characterization of the response in addition to studies aimed at exploring mechanisms of migration were performed. Indeed, electric fields may provide a valuable tool to guide cell movement.", "bbox": [617, 868, 1108, 1130], "page_width": 1224, "page_height": 1584}, "marker_signature": {"type": "none", "raw_marker": null, "number": null, "kind": "generic_text", "normalized_text": "Frenkel and co-workers [3] were the first to demonstrate directed chondrocyte migration. In their chemotaxis studies, chondrocyte movement was directed by a cytokine gradient of bone morphogenic protein (BMP). In a more recent study, cultured chondrocytes have been shown to migrate in response to gradients of extracellular matrix molecules using Boyden chambers [14]. In the present study, our objective was to examine basic science aspects of directed chondrocyte migration to applied electric field gradients using a novel galvanotaxis chamber and time-lapse digital video microscopy. Characterization of the response in addition to studies aimed at exploring mechanisms of migration were performed. Indeed, electric fields may provide a valuable tool to guide cell movement."}, "layout_signature": {"width": 491, "width_bucket": 500, "height": 262, "left": 617, "top": 868, "right": 1108, "bottom": 1130, "x_center": 862.5, "x_center_bucket": 850, "y_center": 999.0, "x_ratio": 0.7047, "y_ratio": 0.6307, "width_ratio": 0.4011, "height_ratio": 0.1654, "line_count": 1}, "span_signature": {"font_size": 8.98, "font_size_median": 8.98, "font_size_bucket": 9.0, "font_family_norm": "Times-Roman", "bold": false, "italic": true, "span_count": 162}, "_in_visual_container": null, "_container_bbox": null, "_container_text": null, "_text_source": null, "_ocr_raw_status": null, "_ocr_raw_error_type": null, "render_default": true, "index_default": true, "zone": "body_zone", "style_family": "body_like", "style_family_authority": "body_zone_with_anchor", "reading_band_id": "band_040", "display_cluster_candidate_id": "", "layout_region": "reference_candidate", "boundary_before": "weak", "boundary_after": "none", "bridge_eligible": false, "insert_score": {"score": 0.15, "decision": "body", "evidence": ["narrow_width"]}, "role_verification_status": "ACCEPT", "role_source": "non_structural_normalized_role", "role_evidence": ["pre-gate normalized non-structural role preserved"]} +{"paper_id": "28JLIHLS", "page": 1, "block_id": 11, "raw_label": "paragraph_title", "raw_order": 12, "bbox": [620, 1150, 829, 1172], "text": "Methods and Materials", "page_width": 1224, "page_height": 1584, "role": "section_heading", "role_confidence": 0.5, "evidence": ["unnumbered paragraph_title on page 1 outside title zone: Methods and Materials"], "seed_role": "section_heading", "seed_confidence": 0.5, "seed_evidence": ["unnumbered paragraph_title on page 1 outside title zone: Methods and Materials"], "span_metadata": [{"size": 9.977999687194824, "font": "Times-Bold", "flags": 20, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 9.977999687194824, "font": "Times-Bold", "flags": 20, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 9.977999687194824, "font": "Times-Bold", "flags": 20, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 9.977999687194824, "font": "Times-Bold", "flags": 20, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 9.977999687194824, "font": "Times-Bold", "flags": 20, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}], "raw_observation": {"block_id": 11, "page": 1, "raw_label": "paragraph_title", "text": "Methods and Materials", "bbox": [620, 1150, 829, 1172], "page_width": 1224, "page_height": 1584}, "marker_signature": {"type": "none", "raw_marker": null, "number": null, "kind": "generic_text", "normalized_text": "Methods and Materials"}, "layout_signature": {"width": 209, "width_bucket": 200, "height": 22, "left": 620, "top": 1150, "right": 829, "bottom": 1172, "x_center": 724.5, "x_center_bucket": 725, "y_center": 1161.0, "x_ratio": 0.5919, "y_ratio": 0.733, "width_ratio": 0.1708, "height_ratio": 0.0139, "line_count": 1}, "span_signature": {"font_size": 9.98, "font_size_median": 9.98, "font_size_bucket": 10.0, "font_family_norm": "Times-Bold", "bold": true, "italic": true, "span_count": 5}, "_in_visual_container": null, "_container_bbox": null, "_container_text": null, "_text_source": null, "_ocr_raw_status": null, "_ocr_raw_error_type": null, "render_default": true, "index_default": true, "zone": "body_zone", "style_family": "heading_like", "style_family_authority": "heading_typography", "reading_band_id": "band_040", "display_cluster_candidate_id": "", "layout_region": "reference_candidate", "boundary_before": "weak", "boundary_after": "none", "bridge_eligible": false, "insert_score": {"score": 0.15, "decision": "body", "evidence": ["narrow_width"]}, "role_verification_status": "ACCEPT", "role_source": "accepted_heading", "role_evidence": ["heading verified by heading artifact"]} +{"paper_id": "28JLIHLS", "page": 1, "block_id": 12, "raw_label": "text", "raw_order": 13, "bbox": [617, 1184, 1107, 1467], "text": "Cell Culture. Primary bovine chondrocytes were isolated from articular cartilage harvested from the carpo-metacarpal joint of freshly killed 4–6 month old bovine calves obtained from a local abattoir and rinsed in Dulbecco's Modified Essential Medium (DMEM) supplemented with 10 percent FBS, amino acids (0.5×minimal essential amino acids, 1×nonessential amino acids), buffering agents (10 mM Hepes, 10 mM sodium bicarbonate, 10 mM TES, 10 mM BES), and antibiotics (100 U/ml penicillin, 100 mg/ml streptomycin). The cartilage chunks were digested with 50 mg of bovine testicular hyaluronidase type I-S (Sigma Chemical Company, St. Louis, MO) in 100 ml of DMEM for 30 minutes at 37°C. After removal of the hyaluronidase solution, the cartilage specimens were digested at 37°C overnight with 50 mg of clostridial collagenase type II (Sigma) in 100 ml of DMEM.", "page_width": 1224, "page_height": 1584, "role": "body_paragraph", "role_confidence": 0.6, "evidence": ["default body_paragraph for text label"], "seed_role": "body_paragraph", "seed_confidence": 0.6, "seed_evidence": ["default body_paragraph for text label"], "span_metadata": [{"size": 8.979999542236328, "font": "Times-Bold", "flags": 20, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 8.979999542236328, "font": "Times-Bold", "flags": 20, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 8.979999542236328, "font": "Times-Bold", "flags": 20, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 8.979999542236328, "font": "Times-Roman", "flags": 4, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 8.979999542236328, "font": "Times-Roman", "flags": 4, "color": 2301728, "dir": [1.0, 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Primary bovine chondrocytes were isolated from articular cartilage harvested from the carpo-metacarpal joint of freshly killed 4–6 month old bovine calves obtained from a local abattoir and rinsed in Dulbecco's Modified Essential Medium (DMEM) supplemented with 10 percent FBS, amino acids (0.5×minimal essential amino acids, 1×nonessential amino acids), buffering agents (10 mM Hepes, 10 mM sodium bicarbonate, 10 mM TES, 10 mM BES), and antibiotics (100 U/ml penicillin, 100 mg/ml streptomycin). The cartilage chunks were digested with 50 mg of bovine testicular hyaluronidase type I-S (Sigma Chemical Company, St. Louis, MO) in 100 ml of DMEM for 30 minutes at 37°C. After removal of the hyaluronidase solution, the cartilage specimens were digested at 37°C overnight with 50 mg of clostridial collagenase type II (Sigma) in 100 ml of DMEM.", "bbox": [617, 1184, 1107, 1467], "page_width": 1224, "page_height": 1584}, "marker_signature": {"type": "none", "raw_marker": null, "number": null, "kind": "generic_text", "normalized_text": "Cell Culture. Primary bovine chondrocytes were isolated from articular cartilage harvested from the carpo-metacarpal joint of freshly killed 4–6 month old bovine calves obtained from a local abattoir and rinsed in Dulbecco's Modified Essential Medium (DMEM) supplemented with 10 percent FBS, amino acids (0.5×minimal essential amino acids, 1×nonessential amino acids), buffering agents (10 mM Hepes, 10 mM sodium bicarbonate, 10 mM TES, 10 mM BES), and antibiotics (100 U/ml penicillin, 100 mg/ml streptomycin). The cartilage chunks were digested with 50 mg of bovine testicular hyaluronidase type I-S (Sigma Chemical Company, St. Louis, MO) in 100 ml of DMEM for 30 minutes at 37°C. After removal of the hyaluronidase solution, the cartilage specimens were digested at 37°C overnight with 50 mg of clostridial collagenase type II (Sigma) in 100 ml of DMEM."}, "layout_signature": {"width": 490, "width_bucket": 500, "height": 283, "left": 617, "top": 1184, "right": 1107, "bottom": 1467, "x_center": 862.0, "x_center_bucket": 850, "y_center": 1325.5, "x_ratio": 0.7042, "y_ratio": 0.8368, "width_ratio": 0.4003, "height_ratio": 0.1787, "line_count": 1}, "span_signature": {"font_size": 8.98, "font_size_median": 8.98, "font_size_bucket": 9.0, "font_family_norm": "Times-Bold", "bold": true, "italic": true, "span_count": 237}, "_in_visual_container": null, "_container_bbox": null, "_container_text": null, "_text_source": null, "_ocr_raw_status": null, "_ocr_raw_error_type": null, "render_default": true, "index_default": true, "zone": "body_zone", "style_family": "body_like", "style_family_authority": "body_zone_with_anchor", "reading_band_id": "band_040", "display_cluster_candidate_id": "", "layout_region": "reference_candidate", "boundary_before": "weak", "boundary_after": "none", "bridge_eligible": false, "insert_score": {"score": 0.15, "decision": "body", "evidence": ["narrow_width"]}, "role_verification_status": "ACCEPT", "role_source": "non_structural_normalized_role", "role_evidence": ["pre-gate normalized non-structural role preserved"]} +{"paper_id": "28JLIHLS", "page": 1, "block_id": 13, "raw_label": "footnote", "raw_order": null, "bbox": [116, 1399, 603, 1467], "text": "Contributed by the Bioengineering Division for publication in the JOURNAL OF BIOMECHANICAL ENGINEERING. Manuscript received by the Bioengineering Division, October 21, 1999; revised manuscript received February 6, 2000. Associate Technical Editor: R. Vanderby, Jr.", "page_width": 1224, "page_height": 1584, "role": "footnote", "role_confidence": 0.7, "evidence": ["footnote label: Contributed by the Bioengineering Division for publication i"], "seed_role": "footnote", "seed_confidence": 0.7, "seed_evidence": ["footnote label: Contributed by the Bioengineering Division for publication i"], "span_metadata": [{"size": 6.985000133514404, "font": "Times-Roman", "flags": 4, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 6.985000133514404, "font": "Times-Roman", "flags": 4, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 6.985000133514404, "font": "Times-Roman", "flags": 4, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 6.985000133514404, "font": "Times-Roman", "flags": 4, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 6.985000133514404, "font": "Times-Roman", "flags": 4, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 6.985000133514404, "font": "Times-Roman", "flags": 4, "color": 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(a) Exploded view of the parallel-plate chamber that permits real-time visualization of migrating cells cultured on a glass slide; (b) Schematic of the galvanotaxis circuit configuration. Current from a power supply is transmitted via Ag–AgCl electrodes bathed in saline reservoirs and linked to the chamber via 2 percent agarose bridges.", "bbox": [116, 653, 603, 785], "page_width": 1224, "page_height": 1584}, "marker_signature": {"type": "figure_number", "raw_marker": "Fig. 1", "number": 1, "kind": "figure", "normalized_text": "Fig. 1 Schematic diagram of the galvanotaxis chamber and system. (a) Exploded view of the parallel-plate chamber that permits real-time visualization of migrating cells cultured on a glass slide; (b) Schematic of the galvanotaxis circuit configuration. Current from a power supply is transmitted via Ag–AgCl electrodes bathed in saline reservoirs and linked to the chamber via 2 percent agarose bridges."}, "layout_signature": {"width": 487, "width_bucket": 475, "height": 132, "left": 116, "top": 653, "right": 603, "bottom": 785, "x_center": 359.5, "x_center_bucket": 350, "y_center": 719.0, "x_ratio": 0.2937, "y_ratio": 0.4539, "width_ratio": 0.3979, "height_ratio": 0.0833, "line_count": 1}, "span_signature": {"font_size": 7.98, "font_size_median": 7.98, "font_size_bucket": 8.0, "font_family_norm": "Helvetica-Bold", "bold": true, "italic": true, "span_count": 102}, "_in_visual_container": null, "_container_bbox": null, "_container_text": null, "_text_source": null, "_ocr_raw_status": null, "_ocr_raw_error_type": null, "render_default": true, "index_default": true, "zone": "display_zone", "style_family": "legend_like", "style_family_authority": "figure_marker", "reading_band_id": "band_039", "display_cluster_candidate_id": "", "layout_region": "reference_candidate", "boundary_before": "weak", "boundary_after": "none", "bridge_eligible": false, "insert_score": {"score": 0.15, "decision": "body", "evidence": ["narrow_width"]}, "role_verification_status": "ACCEPT", "role_source": "accepted_figure_caption_artifact", "role_evidence": ["figure caption matched accepted figure artifact"]} +{"paper_id": "28JLIHLS", "page": 2, "block_id": 3, "raw_label": "text", "raw_order": 1, "bbox": [114, 840, 604, 1043], "text": "The cell suspension was sedimented in a benchtop clinical centrifuge at 4°C for 5 minutes. For electric field studies, cells were released from high density monolayer cultures using a trypsin/EDTA solution and plated at 50,000 cells/cm² on to sterile glass slides (Fisher Scientific) using removable Flexiperm silicone vessels (Heraeus). After attachment for 45 minutes in a 5 percent CO₂ incubator at 37°C, the slide was gently rinsed with medium and then positioned in a custom galvanotaxis chamber, which was assembled under a sterile laminar flow hood. First passage cells were used in all studies described below.", "page_width": 1224, "page_height": 1584, "role": "body_paragraph", "role_confidence": 0.6, "evidence": ["default body_paragraph for text label"], "seed_role": "body_paragraph", "seed_confidence": 0.6, "seed_evidence": ["default body_paragraph for text label"], "span_metadata": [{"size": 8.979999542236328, "font": "Times-Roman", "flags": 4, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 8.979999542236328, "font": "Times-Roman", "flags": 4, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 8.979999542236328, "font": "Times-Roman", "flags": 4, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 8.979999542236328, "font": "Times-Roman", "flags": 4, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 8.979999542236328, "font": "Times-Roman", "flags": 4, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 8.979999542236328, "font": "Times-Roman", "flags": 4, "color": 2301728, "dir": 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"text", "text": "The cell suspension was sedimented in a benchtop clinical centrifuge at 4°C for 5 minutes. For electric field studies, cells were released from high density monolayer cultures using a trypsin/EDTA solution and plated at 50,000 cells/cm² on to sterile glass slides (Fisher Scientific) using removable Flexiperm silicone vessels (Heraeus). After attachment for 45 minutes in a 5 percent CO₂ incubator at 37°C, the slide was gently rinsed with medium and then positioned in a custom galvanotaxis chamber, which was assembled under a sterile laminar flow hood. First passage cells were used in all studies described below.", "bbox": [114, 840, 604, 1043], "page_width": 1224, "page_height": 1584}, "marker_signature": {"type": "none", "raw_marker": null, "number": null, "kind": "generic_text", "normalized_text": "The cell suspension was sedimented in a benchtop clinical centrifuge at 4°C for 5 minutes. For electric field studies, cells were released from high density monolayer cultures using a trypsin/EDTA solution and plated at 50,000 cells/cm² on to sterile glass slides (Fisher Scientific) using removable Flexiperm silicone vessels (Heraeus). After attachment for 45 minutes in a 5 percent CO₂ incubator at 37°C, the slide was gently rinsed with medium and then positioned in a custom galvanotaxis chamber, which was assembled under a sterile laminar flow hood. First passage cells were used in all studies described below."}, "layout_signature": {"width": 490, "width_bucket": 500, "height": 203, "left": 114, "top": 840, "right": 604, "bottom": 1043, "x_center": 359.0, "x_center_bucket": 350, "y_center": 941.5, "x_ratio": 0.2933, "y_ratio": 0.5944, "width_ratio": 0.4003, "height_ratio": 0.1282, "line_count": 1}, "span_signature": {"font_size": 8.95, "font_size_median": 8.98, "font_size_bucket": 9.0, "font_family_norm": "Times-Roman", "bold": false, "italic": true, "span_count": 172}, "_in_visual_container": null, "_container_bbox": null, "_container_text": null, "_text_source": null, "_ocr_raw_status": null, "_ocr_raw_error_type": null, "render_default": true, "index_default": true, "zone": "body_zone", "style_family": "body_like", "style_family_authority": "body_zone_with_anchor", "reading_band_id": "band_039", "display_cluster_candidate_id": "", "layout_region": "reference_candidate", "boundary_before": "weak", "boundary_after": "none", "bridge_eligible": false, "insert_score": {"score": 0.15, "decision": "body", "evidence": ["narrow_width"]}, "role_verification_status": "ACCEPT", "role_source": "non_structural_normalized_role", "role_evidence": ["pre-gate normalized non-structural role preserved"]} +{"paper_id": "28JLIHLS", "page": 2, "block_id": 4, "raw_label": "text", "raw_order": 2, "bbox": [114, 1053, 603, 1314], "text": "Galvanotaxis Chamber. A modified parallel-plate flow chamber was used to introduce prescribed electric fields to chondrocytes cultured on glass slides [15], see Fig. 1. One plate of the chamber consisted of a Plexiglas block with a glass window while the glass slide substrate represented the second plate. The plates were separated by a uniform thickness rectangular silastic spacer (McMaster-Carr, New Brunswick, NJ), held together with screws and a Plexiglas lid (having a hole to accommodate the microscope objective), thereby creating a sealed rectangular channel with dimensions of $ 5 \\times 10^{-2} $ m, $ 1.3 \\times 10^{-2} $ m, $ 2.50 \\times 10^{-4} $ m (length, width, and height or gap distance). 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A modified parallel-plate flow chamber was used to introduce prescribed electric fields to chondrocytes cultured on glass slides [15], see Fig. 1. One plate of the chamber consisted of a Plexiglas block with a glass window while the glass slide substrate represented the second plate. The plates were separated by a uniform thickness rectangular silastic spacer (McMaster-Carr, New Brunswick, NJ), held together with screws and a Plexiglas lid (having a hole to accommodate the microscope objective), thereby creating a sealed rectangular channel with dimensions of $ 5 \\times 10^{-2} $ m, $ 1.3 \\times 10^{-2} $ m, $ 2.50 \\times 10^{-4} $ m (length, width, and height or gap distance). The well-defined chamber geometry permitted the electric field strength or current density to be calculated.", "bbox": [114, 1053, 603, 1314], "page_width": 1224, "page_height": 1584}, "marker_signature": {"type": "none", "raw_marker": null, "number": null, "kind": "generic_text", "normalized_text": "Galvanotaxis Chamber. A modified parallel-plate flow chamber was used to introduce prescribed electric fields to chondrocytes cultured on glass slides [15], see Fig. 1. One plate of the chamber consisted of a Plexiglas block with a glass window while the glass slide substrate represented the second plate. The plates were separated by a uniform thickness rectangular silastic spacer (McMaster-Carr, New Brunswick, NJ), held together with screws and a Plexiglas lid (having a hole to accommodate the microscope objective), thereby creating a sealed rectangular channel with dimensions of $ 5 \\times 10^{-2} $ m, $ 1.3 \\times 10^{-2} $ m, $ 2.50 \\times 10^{-4} $ m (length, width, and height or gap distance). The well-defined chamber geometry permitted the electric field strength or current density to be calculated."}, "layout_signature": {"width": 489, "width_bucket": 500, "height": 261, "left": 114, "top": 1053, "right": 603, "bottom": 1314, "x_center": 358.5, "x_center_bucket": 350, "y_center": 1183.5, "x_ratio": 0.2929, "y_ratio": 0.7472, "width_ratio": 0.3995, "height_ratio": 0.1648, "line_count": 1}, "span_signature": {"font_size": 8.88, "font_size_median": 8.98, "font_size_bucket": 9.0, "font_family_norm": "Times-Bold", "bold": true, "italic": true, "span_count": 160}, "_in_visual_container": null, "_container_bbox": null, "_container_text": null, "_text_source": null, "_ocr_raw_status": null, "_ocr_raw_error_type": null, "render_default": true, "index_default": true, "zone": "body_zone", "style_family": "body_like", "style_family_authority": "body_family_anchor", "reading_band_id": "band_039", "display_cluster_candidate_id": "", "layout_region": "reference_candidate", "boundary_before": "weak", "boundary_after": "none", "bridge_eligible": false, "insert_score": {"score": 0.15, "decision": "body", "evidence": ["narrow_width"]}, "role_verification_status": "ACCEPT", "role_source": "non_structural_normalized_role", "role_evidence": ["pre-gate normalized non-structural role preserved"]} +{"paper_id": "28JLIHLS", "page": 2, "block_id": 5, "raw_label": "text", "raw_order": 3, "bbox": [114, 1325, 603, 1468], "text": "Electric Field Studies. Silver–silver chloride electrodes were fashioned out of gauge 23 (0.025 $ ^{\\circ} $) silver wire soaked for 1 hour in a hypochlorite solution (Clorox), as previously described [16] and interfaced with luer ports on each side of the galvanotaxis channel via a pair of 35 cm long, 2 percent agarose–saline bridges. A Biorad power supply (PowerPac 300) was used to apply currents up to 5 mA through the chamber. The 2 percent agarose–saline bridges and saline reservoirs prevented contamination of the cells from electrolysis products generated during current application. These methods are described in greater detail in Hung et al. [6]. The resistance of the chamber was $ \\sim $8 k $ \\Omega $, which is consistent with theoretical calculations derived from the conductivity of the medium and chamber geometry. Multimeters positioned in series and in parallel with the chamber permitted the applied current and the field strength, respectively, to be monitored and adjusted during experiments.", "page_width": 1224, "page_height": 1584, "role": "body_paragraph", "role_confidence": 0.6, "evidence": ["default body_paragraph for text label"], "seed_role": "body_paragraph", "seed_confidence": 0.6, "seed_evidence": ["default body_paragraph for text label"], "span_metadata": [{"size": 8.979999542236328, "font": "Times-Bold", "flags": 20, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 8.979999542236328, "font": "Times-Roman", "flags": 4, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 8.979999542236328, "font": "Times-Roman", "flags": 4, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 8.979999542236328, "font": "Times-Roman", "flags": 4, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 8.979999542236328, "font": "Times-Roman", "flags": 4, "color": 2301728, 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Silver–silver chloride electrodes were fashioned out of gauge 23 (0.025 $ ^{\\circ} $) silver wire soaked for 1 hour in a hypochlorite solution (Clorox), as previously described [16] and interfaced with luer ports on each side of the galvanotaxis channel via a pair of 35 cm long, 2 percent agarose–saline bridges. A Biorad power supply (PowerPac 300) was used to apply currents up to 5 mA through the chamber. The 2 percent agarose–saline bridges and saline reservoirs prevented contamination of the cells from electrolysis products generated during current application. These methods are described in greater detail in Hung et al. [6]. The resistance of the chamber was $ \\sim $8 k $ \\Omega $, which is consistent with theoretical calculations derived from the conductivity of the medium and chamber geometry. 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These methods are described in greater detail in Hung et al. [6]. The resistance of the chamber was $ \\sim $8 k $ \\Omega $, which is consistent with theoretical calculations derived from the conductivity of the medium and chamber geometry. 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Experiments were performed at room temperature (~25°C) or at 37°C. For the latter, a heat gun in conjunction with a partially enclosing Styrofoam barrier was used to maintain the stage and chamber at 37°C. Currents were applied for 2 hours, generating a constant field strength of 0, 0.17, 0.8, 2, 4 and 6 V/cm (corresponding to J=0, 0.003, 0.012, 0.03, 0.07 and 0.1 A/cm² respectively).", "bbox": [619, 256, 1107, 445], "page_width": 1224, "page_height": 1584}, "marker_signature": {"type": "none", "raw_marker": null, "number": null, "kind": "generic_text", "normalized_text": "After securing the Plexiglas lid side of the chamber on the microscope stage, the cells were permitted to equilibrate for an additional 30 minutes before studies were initiated. Experiments were performed at room temperature (~25°C) or at 37°C. For the latter, a heat gun in conjunction with a partially enclosing Styrofoam barrier was used to maintain the stage and chamber at 37°C. Currents were applied for 2 hours, generating a constant field strength of 0, 0.17, 0.8, 2, 4 and 6 V/cm (corresponding to J=0, 0.003, 0.012, 0.03, 0.07 and 0.1 A/cm² respectively)."}, "layout_signature": {"width": 488, "width_bucket": 500, "height": 189, "left": 619, "top": 256, "right": 1107, "bottom": 445, "x_center": 863.0, "x_center_bucket": 875, "y_center": 350.5, "x_ratio": 0.7051, "y_ratio": 0.2213, "width_ratio": 0.3987, "height_ratio": 0.1193, "line_count": 1}, "span_signature": {"font_size": 8.97, "font_size_median": 8.98, "font_size_bucket": 9.0, "font_family_norm": "Times-Roman", "bold": false, "italic": true, "span_count": 183}, "_in_visual_container": null, "_container_bbox": null, "_container_text": null, "_text_source": null, "_ocr_raw_status": null, "_ocr_raw_error_type": null, "render_default": true, "index_default": true, "zone": "body_zone", "style_family": "body_like", "style_family_authority": "body_zone_with_anchor", "reading_band_id": "band_039", "display_cluster_candidate_id": "", "layout_region": "reference_candidate", "boundary_before": "weak", "boundary_after": "none", "bridge_eligible": false, "insert_score": {"score": 0.15, "decision": "body", "evidence": ["narrow_width"]}, "role_verification_status": "ACCEPT", "role_source": "non_structural_normalized_role", "role_evidence": ["pre-gate normalized non-structural role preserved"]} +{"paper_id": "28JLIHLS", "page": 2, "block_id": 8, "raw_label": "text", "raw_order": 6, "bbox": [617, 457, 1107, 806], "text": "Inhibitor Studies. The phospholipase-C specific inhibitor, U-73122 (20 $ \\mu $M, Sigma Chemical) was adopted in some studies to investigate the role of the inositol phospholipid pathway in mediating chondrocyte electric-field induced migration. The drug was solubilized in DMSO (<0.2 percent by volume) and added to the conducting solution. The effect of neomycin (1 mM, Sigma Chemical), a less specific inhibitor of the inositol phospholipid pathway, was also explored [17–19]. Neomycin, an aminoglycoside antibiotic, has been demonstrated to affect nerve growth, orientation and branching under applied electric fields [18]. Cells were incubated for 30 minutes in the incubator with fully supplemented tissue culture medium and then for 15 minutes with medium containing inhibitor or vehicle. The slide was then positioned in the chamber filled with medium containing inhibitor or vehicle. 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"color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 8.979999542236328, "font": "Times-Roman", "flags": 4, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}], "raw_observation": {"block_id": 8, "page": 2, "raw_label": "text", "text": "Inhibitor Studies. The phospholipase-C specific inhibitor, U-73122 (20 $ \\mu $M, Sigma Chemical) was adopted in some studies to investigate the role of the inositol phospholipid pathway in mediating chondrocyte electric-field induced migration. The drug was solubilized in DMSO (<0.2 percent by volume) and added to the conducting solution. The effect of neomycin (1 mM, Sigma Chemical), a less specific inhibitor of the inositol phospholipid pathway, was also explored [17–19]. Neomycin, an aminoglycoside antibiotic, has been demonstrated to affect nerve growth, orientation and branching under applied electric fields [18]. Cells were incubated for 30 minutes in the incubator with fully supplemented tissue culture medium and then for 15 minutes with medium containing inhibitor or vehicle. The slide was then positioned in the chamber filled with medium containing inhibitor or vehicle. The assembled chamber was permitted to equilibrate on the heated microscope stage for an additional 30 minutes before experiments were initiated.", "bbox": [617, 457, 1107, 806], "page_width": 1224, "page_height": 1584}, "marker_signature": {"type": "none", "raw_marker": null, "number": null, "kind": "generic_text", "normalized_text": "Inhibitor Studies. The phospholipase-C specific inhibitor, U-73122 (20 $ \\mu $M, Sigma Chemical) was adopted in some studies to investigate the role of the inositol phospholipid pathway in mediating chondrocyte electric-field induced migration. The drug was solubilized in DMSO (<0.2 percent by volume) and added to the conducting solution. The effect of neomycin (1 mM, Sigma Chemical), a less specific inhibitor of the inositol phospholipid pathway, was also explored [17–19]. Neomycin, an aminoglycoside antibiotic, has been demonstrated to affect nerve growth, orientation and branching under applied electric fields [18]. Cells were incubated for 30 minutes in the incubator with fully supplemented tissue culture medium and then for 15 minutes with medium containing inhibitor or vehicle. The slide was then positioned in the chamber filled with medium containing inhibitor or vehicle. The assembled chamber was permitted to equilibrate on the heated microscope stage for an additional 30 minutes before experiments were initiated."}, "layout_signature": {"width": 490, "width_bucket": 500, "height": 349, "left": 617, "top": 457, "right": 1107, "bottom": 806, "x_center": 862.0, "x_center_bucket": 850, "y_center": 631.5, "x_ratio": 0.7042, "y_ratio": 0.3987, "width_ratio": 0.4003, "height_ratio": 0.2203, "line_count": 1}, "span_signature": {"font_size": 8.98, "font_size_median": 8.98, "font_size_bucket": 9.0, "font_family_norm": "Times-Bold", "bold": true, "italic": true, "span_count": 269}, "_in_visual_container": null, "_container_bbox": null, "_container_text": null, "_text_source": null, "_ocr_raw_status": null, "_ocr_raw_error_type": null, "render_default": true, "index_default": true, "zone": "body_zone", "style_family": "body_like", "style_family_authority": "body_zone_with_anchor", "reading_band_id": "band_039", "display_cluster_candidate_id": "", "layout_region": "reference_candidate", "boundary_before": "weak", "boundary_after": "none", "bridge_eligible": false, "insert_score": {"score": 0.15, "decision": "body", "evidence": ["narrow_width"]}, "role_verification_status": "ACCEPT", "role_source": "non_structural_normalized_role", "role_evidence": ["pre-gate normalized non-structural role preserved"]} +{"paper_id": "28JLIHLS", "page": 2, "block_id": 9, "raw_label": "text", "raw_order": 7, "bbox": [617, 816, 1107, 1045], "text": "Digital Video Microscopy. Cell migration was recorded using an Olympus IX-70 inverted microscope equipped with a MicroMax 5-MHz interline transfer chip digital camera (Princeton Instruments, NJ) linked to a computer running Metamorph software (Universal Imaging, Westchester, PA). The glass window in the back of the Plexiglas chamber permitted cell imaging using Hoffman contrast optics and a 10×objective (1 pixel=0.68 microns). Approximately 40–60 cells were observed in a given field of view. The displacement of the centroid for each cell was recorded every 10 minutes for the two-hour experiments.", "page_width": 1224, "page_height": 1584, "role": "body_paragraph", "role_confidence": 0.6, "evidence": ["default body_paragraph for text label"], "seed_role": "body_paragraph", "seed_confidence": 0.6, "seed_evidence": ["default body_paragraph for text label"], "span_metadata": [{"size": 8.979999542236328, "font": "Times-Bold", "flags": 20, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 8.979999542236328, "font": "Times-Bold", "flags": 20, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 8.979999542236328, "font": "Times-Bold", "flags": 20, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 8.979999542236328, "font": "Times-Bold", "flags": 20, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 8.979999542236328, "font": "Times-Bold", "flags": 20, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 8.979999542236328, "font": 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Cell migration was recorded using an Olympus IX-70 inverted microscope equipped with a MicroMax 5-MHz interline transfer chip digital camera (Princeton Instruments, NJ) linked to a computer running Metamorph software (Universal Imaging, Westchester, PA). The glass window in the back of the Plexiglas chamber permitted cell imaging using Hoffman contrast optics and a 10×objective (1 pixel=0.68 microns). Approximately 40–60 cells were observed in a given field of view. The displacement of the centroid for each cell was recorded every 10 minutes for the two-hour experiments.", "bbox": [617, 816, 1107, 1045], "page_width": 1224, "page_height": 1584}, "marker_signature": {"type": "none", "raw_marker": null, "number": null, "kind": "generic_text", "normalized_text": "Digital Video Microscopy. Cell migration was recorded using an Olympus IX-70 inverted microscope equipped with a MicroMax 5-MHz interline transfer chip digital camera (Princeton Instruments, NJ) linked to a computer running Metamorph software (Universal Imaging, Westchester, PA). The glass window in the back of the Plexiglas chamber permitted cell imaging using Hoffman contrast optics and a 10×objective (1 pixel=0.68 microns). Approximately 40–60 cells were observed in a given field of view. The displacement of the centroid for each cell was recorded every 10 minutes for the two-hour experiments."}, "layout_signature": {"width": 490, "width_bucket": 500, "height": 229, "left": 617, "top": 816, "right": 1107, "bottom": 1045, "x_center": 862.0, "x_center_bucket": 850, "y_center": 930.5, "x_ratio": 0.7042, "y_ratio": 0.5874, "width_ratio": 0.4003, "height_ratio": 0.1446, "line_count": 1}, "span_signature": {"font_size": 8.98, "font_size_median": 8.98, "font_size_bucket": 9.0, "font_family_norm": "Times-Bold", "bold": true, "italic": true, "span_count": 169}, "_in_visual_container": null, "_container_bbox": null, "_container_text": null, "_text_source": null, "_ocr_raw_status": null, "_ocr_raw_error_type": null, "render_default": true, "index_default": true, "zone": "body_zone", "style_family": "body_like", "style_family_authority": "body_zone_with_anchor", "reading_band_id": "band_039", "display_cluster_candidate_id": "", "layout_region": "reference_candidate", "boundary_before": "weak", "boundary_after": "none", "bridge_eligible": false, "insert_score": {"score": 0.15, "decision": "body", "evidence": ["narrow_width"]}, "role_verification_status": "ACCEPT", "role_source": "non_structural_normalized_role", "role_evidence": ["pre-gate normalized non-structural role preserved"]} +{"paper_id": "28JLIHLS", "page": 2, "block_id": 10, "raw_label": "text", "raw_order": 8, "bbox": [615, 1054, 1107, 1467], "text": "Data Analysis. The speed of migration for each cell was obtained by measuring the net centroid displacement from origin to end point at 2 hours. The migration direction was quantified in terms of sine( $ \\varphi $) where the value was -1 (corresponding to $ \\varphi = -90 $deg) in the direction of the cathode. The directed velocity (i.e., the component of the speed directed toward the negative pole) was obtained by multiplying the cell speed by sine( $ \\varphi $). Thus, a negative directed velocity indicates cathodal migration. Centroids were manually digitized and processed using MetaMorph linked to an Excel spreadsheet. Statistics were performed using Systat 5. Mean data was analyzed using one way analysis of variance and Fishers least significant difference test with $ \\alpha = 0.05 $. Standard deviations for n = number of cells are provided in the text and figures. Polar plots of net cell displacement, where +90 deg is the anode and -90 deg is the cathode, are depicted in some figures. A cell which remained stationary over the duration of an experiment would have a zero net displacement and be designated by a sphere symbol at the center of the polar plot (0 $ \\mu $m, 0 deg). Each data set represents cells pooled from at least three separate experimental runs.", "page_width": 1224, "page_height": 1584, "role": "body_paragraph", "role_confidence": 0.6, "evidence": ["default body_paragraph for text label"], "seed_role": "body_paragraph", "seed_confidence": 0.6, "seed_evidence": ["default body_paragraph for text label"], "span_metadata": [{"size": 8.979999542236328, "font": "Times-Bold", "flags": 20, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 8.979999542236328, "font": "Times-Bold", "flags": 20, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 8.979999542236328, "font": "Times-Bold", "flags": 20, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 8.979999542236328, "font": "Times-Roman", "flags": 4, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 8.979999542236328, "font": "Times-Roman", "flags": 4, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 8.979999542236328, "font": "Times-Roman", "flags": 4, 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8.979999542236328, "font": "Times-Roman", "flags": 4, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 8.979999542236328, "font": "Times-Roman", "flags": 4, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 8.979999542236328, "font": "Times-Roman", "flags": 4, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}], "raw_observation": {"block_id": 10, "page": 2, "raw_label": "text", "text": "Data Analysis. The speed of migration for each cell was obtained by measuring the net centroid displacement from origin to end point at 2 hours. The migration direction was quantified in terms of sine( $ \\varphi $) where the value was -1 (corresponding to $ \\varphi = -90 $deg) in the direction of the cathode. The directed velocity (i.e., the component of the speed directed toward the negative pole) was obtained by multiplying the cell speed by sine( $ \\varphi $). Thus, a negative directed velocity indicates cathodal migration. Centroids were manually digitized and processed using MetaMorph linked to an Excel spreadsheet. Statistics were performed using Systat 5. Mean data was analyzed using one way analysis of variance and Fishers least significant difference test with $ \\alpha = 0.05 $. Standard deviations for n = number of cells are provided in the text and figures. Polar plots of net cell displacement, where +90 deg is the anode and -90 deg is the cathode, are depicted in some figures. A cell which remained stationary over the duration of an experiment would have a zero net displacement and be designated by a sphere symbol at the center of the polar plot (0 $ \\mu $m, 0 deg). Each data set represents cells pooled from at least three separate experimental runs.", "bbox": [615, 1054, 1107, 1467], "page_width": 1224, "page_height": 1584}, "marker_signature": {"type": "none", "raw_marker": null, "number": null, "kind": "generic_text", "normalized_text": "Data Analysis. The speed of migration for each cell was obtained by measuring the net centroid displacement from origin to end point at 2 hours. The migration direction was quantified in terms of sine( $ \\varphi $) where the value was -1 (corresponding to $ \\varphi = -90 $deg) in the direction of the cathode. The directed velocity (i.e., the component of the speed directed toward the negative pole) was obtained by multiplying the cell speed by sine( $ \\varphi $). Thus, a negative directed velocity indicates cathodal migration. Centroids were manually digitized and processed using MetaMorph linked to an Excel spreadsheet. Statistics were performed using Systat 5. Mean data was analyzed using one way analysis of variance and Fishers least significant difference test with $ \\alpha = 0.05 $. Standard deviations for n = number of cells are provided in the text and figures. Polar plots of net cell displacement, where +90 deg is the anode and -90 deg is the cathode, are depicted in some figures. A cell which remained stationary over the duration of an experiment would have a zero net displacement and be designated by a sphere symbol at the center of the polar plot (0 $ \\mu $m, 0 deg). 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The cell exhibits migration toward the cathode, extension of cytoplasmic processes, in serum supplemented DMEM at room temperature (~25°C). Cell migration at physiologic temperatures (~37°C) was nearly doubled.", "bbox": [114, 255, 604, 383], "page_width": 1224, "page_height": 1584}, "marker_signature": {"type": "figure_number", "raw_marker": "Fig. 2", "number": 2, "kind": "figure", "normalized_text": "Fig. 2 A series of Hoffman contrast images (10×, digitally magnified 400 percent) of a chondrocyte at t=0, 30 and 60 minutes after a DC electric field was turned on (field strength of 6 V/cm). The cell exhibits migration toward the cathode, extension of cytoplasmic processes, in serum supplemented DMEM at room temperature (~25°C). Cell migration at physiologic temperatures (~37°C) was nearly doubled."}, "layout_signature": {"width": 490, "width_bucket": 500, "height": 128, "left": 114, "top": 255, "right": 604, "bottom": 383, "x_center": 359.0, "x_center_bucket": 350, "y_center": 319.0, "x_ratio": 0.2933, "y_ratio": 0.2014, "width_ratio": 0.4003, "height_ratio": 0.0808, "line_count": 1}, "span_signature": {"font_size": 7.98, "font_size_median": 7.98, "font_size_bucket": 8.0, "font_family_norm": "Helvetica-Bold", "bold": true, "italic": true, "span_count": 119}, "_in_visual_container": null, "_container_bbox": null, "_container_text": null, "_text_source": null, "_ocr_raw_status": null, "_ocr_raw_error_type": null, "render_default": true, "index_default": true, "zone": "display_zone", "style_family": "legend_like", "style_family_authority": "figure_marker", "reading_band_id": "band_039", "display_cluster_candidate_id": "", "layout_region": "reference_candidate", "boundary_before": "weak", "boundary_after": "none", "bridge_eligible": false, "insert_score": {"score": 0.15, "decision": "body", "evidence": ["narrow_width"]}, "role_verification_status": "ACCEPT", "role_source": "accepted_figure_caption_artifact", "role_evidence": ["figure caption matched accepted figure artifact"]} +{"paper_id": "28JLIHLS", "page": 3, "block_id": 2, "raw_label": "paragraph_title", "raw_order": 1, "bbox": [116, 422, 187, 444], "text": "Results", "page_width": 1224, "page_height": 1584, "role": "section_heading", "role_confidence": 0.9, "evidence": ["explicit scholarly heading: Results"], "seed_role": "section_heading", "seed_confidence": 0.9, "seed_evidence": ["explicit scholarly heading: Results"], "span_metadata": [{"size": 9.977999687194824, "font": "Times-Bold", "flags": 20, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}], "raw_observation": {"block_id": 2, "page": 3, "raw_label": "paragraph_title", "text": "Results", "bbox": [116, 422, 187, 444], "page_width": 1224, "page_height": 1584}, "marker_signature": {"type": "canonical_section_name", "raw_marker": "Results", "number": null, "kind": "heading", "normalized_text": "Results"}, "layout_signature": {"width": 71, "width_bucket": 75, "height": 22, "left": 116, "top": 422, "right": 187, "bottom": 444, "x_center": 151.5, "x_center_bucket": 150, "y_center": 433.0, "x_ratio": 0.1238, "y_ratio": 0.2734, "width_ratio": 0.058, "height_ratio": 0.0139, "line_count": 1}, "span_signature": {"font_size": 9.98, "font_size_median": 9.98, "font_size_bucket": 10.0, "font_family_norm": "Times-Bold", "bold": true, "italic": true, "span_count": 1}, "_in_visual_container": null, "_container_bbox": null, "_container_text": null, "_text_source": null, "_ocr_raw_status": null, "_ocr_raw_error_type": null, "render_default": true, "index_default": true, "zone": "body_zone", "style_family": "heading_like", "style_family_authority": "heading_marker", "reading_band_id": "band_039", "display_cluster_candidate_id": "", "layout_region": "reference_candidate", "boundary_before": "weak", "boundary_after": "none", "bridge_eligible": false, "insert_score": {"score": 0.15, "decision": "body", "evidence": ["narrow_width"]}, "role_verification_status": "ACCEPT", "role_source": "accepted_heading", "role_evidence": ["heading verified by heading artifact"]} +{"paper_id": "28JLIHLS", "page": 3, "block_id": 3, "raw_label": "text", "raw_order": 2, "bbox": [113, 456, 604, 881], "text": "Cathodal Migration and Perpendicular Alignment. Many cultured chondrocytes exposed to a DC electric field migrated in the direction of the cathode, establishing pseudopodia and lamellipodia at their leading edge and often exhibiting ruffled borders at their trailing edge, see Fig. 2. In contrast, chondrocytes subjected to identical experimental conditions in the absence of field application exhibited randomly directed migration, see Fig. 4 (0 V/cm). Cells subjected to electric fields were viable as assessed via trypan blue exclusion as well as the fact that they remained attached. Poorly attached cells became immediately detached from the glass substrate upon field application and floated away in the direction of the anode. After one hour of field application, some cells began to display elongation (with narrowing) perpendicular to the applied field, see Fig. 3. With increasing duration of field application, more cells displayed perpendicular alignment. No detectable changes in pH or temperature of the medium were detected in the experiments. Alternating the negative and positive leads of the power supply yielded the same cathodal migration observation. In addition, no variability between studies performed with cells obtained from different isolations was observed. Similarly, there was little day-to-day variability in the response to applied fields.", "page_width": 1224, "page_height": 1584, "role": "body_paragraph", "role_confidence": 0.6, "evidence": ["default body_paragraph for text label"], "seed_role": "body_paragraph", "seed_confidence": 0.6, "seed_evidence": ["default body_paragraph for text label"], "span_metadata": [{"size": 8.979999542236328, "font": "Times-Bold", "flags": 20, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 8.979999542236328, "font": "Times-Bold", "flags": 20, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 8.979999542236328, "font": "Times-Bold", "flags": 20, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 8.979999542236328, "font": "Times-Bold", "flags": 20, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 8.979999542236328, "font": "Times-Bold", "flags": 20, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 8.979999542236328, "font": "Times-Bold", "flags": 20, 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"Cathodal Migration and Perpendicular Alignment. Many cultured chondrocytes exposed to a DC electric field migrated in the direction of the cathode, establishing pseudopodia and lamellipodia at their leading edge and often exhibiting ruffled borders at their trailing edge, see Fig. 2. In contrast, chondrocytes subjected to identical experimental conditions in the absence of field application exhibited randomly directed migration, see Fig. 4 (0 V/cm). Cells subjected to electric fields were viable as assessed via trypan blue exclusion as well as the fact that they remained attached. Poorly attached cells became immediately detached from the glass substrate upon field application and floated away in the direction of the anode. After one hour of field application, some cells began to display elongation (with narrowing) perpendicular to the applied field, see Fig. 3. With increasing duration of field application, more cells displayed perpendicular alignment. No detectable changes in pH or temperature of the medium were detected in the experiments. Alternating the negative and positive leads of the power supply yielded the same cathodal migration observation. In addition, no variability between studies performed with cells obtained from different isolations was observed. Similarly, there was little day-to-day variability in the response to applied fields.", "bbox": [113, 456, 604, 881], "page_width": 1224, "page_height": 1584}, "marker_signature": {"type": "none", "raw_marker": null, "number": null, "kind": "generic_text", "normalized_text": "Cathodal Migration and Perpendicular Alignment. Many cultured chondrocytes exposed to a DC electric field migrated in the direction of the cathode, establishing pseudopodia and lamellipodia at their leading edge and often exhibiting ruffled borders at their trailing edge, see Fig. 2. In contrast, chondrocytes subjected to identical experimental conditions in the absence of field application exhibited randomly directed migration, see Fig. 4 (0 V/cm). Cells subjected to electric fields were viable as assessed via trypan blue exclusion as well as the fact that they remained attached. Poorly attached cells became immediately detached from the glass substrate upon field application and floated away in the direction of the anode. After one hour of field application, some cells began to display elongation (with narrowing) perpendicular to the applied field, see Fig. 3. With increasing duration of field application, more cells displayed perpendicular alignment. No detectable changes in pH or temperature of the medium were detected in the experiments. Alternating the negative and positive leads of the power supply yielded the same cathodal migration observation. In addition, no variability between studies performed with cells obtained from different isolations was observed. 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Field strength (V/km)Number of cellsSine ( $ \\varphi $)Speed ( $ \\mu $m/h)Directed velocity ( $ \\mu $m/h)
01080.26 $ \\pm $ 0.995.50 $ \\pm $ 4.650.95 $ \\pm $ 5.3
0.171220.071 $ \\pm $ 0.967.04 $ \\pm $ 5.060.49 $ \\pm $ 5.72
0.8173-0.078 $ \\pm $ 0.988.17 $ \\pm $ 6.92-1.81 $ \\pm $ 8.10 $ * $
2187-0.22 $ \\pm $ 0.947.19 $ \\pm $ 4.52-1.72 $ \\pm $ 6.66
4182-0.59 $ \\pm $ 0.99 $ \\# $8.79 $ \\pm $ 5.77 $ * $-3.66 $ \\pm $ 7.34 $ \\# $
6184-0.94 $ \\pm $ 0.83 $ \\# $13.74 $ \\pm $ 8.80 $ \\# $-10.85 $ \\pm $ 9.74 $ \\# $
10 $ \\ast\\ast $53-0.95 $ \\pm $ 0.9823.54 $ \\pm $ 11.03-17.59 $ \\pm $ 15.35
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Field strength (V/km)Number of cellsSine ( $ \\varphi $)Speed ( $ \\mu $m/h)Directed velocity ( $ \\mu $m/h)
01080.26 $ \\pm $ 0.995.50 $ \\pm $ 4.650.95 $ \\pm $ 5.3
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0.8173-0.078 $ \\pm $ 0.988.17 $ \\pm $ 6.92-1.81 $ \\pm $ 8.10 $ * $
2187-0.22 $ \\pm $ 0.947.19 $ \\pm $ 4.52-1.72 $ \\pm $ 6.66
4182-0.59 $ \\pm $ 0.99 $ \\# $8.79 $ \\pm $ 5.77 $ * $-3.66 $ \\pm $ 7.34 $ \\# $
6184-0.94 $ \\pm $ 0.83 $ \\# $13.74 $ \\pm $ 8.80 $ \\# $-10.85 $ \\pm $ 9.74 $ \\# $
10 $ \\ast\\ast $53-0.95 $ \\pm $ 0.9823.54 $ \\pm $ 11.03-17.59 $ \\pm $ 15.35
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Field strength (V/km)Number of cellsSine ( $ \\varphi $)Speed ( $ \\mu $m/h)Directed velocity ( $ \\mu $m/h)
01080.26 $ \\pm $ 0.995.50 $ \\pm $ 4.650.95 $ \\pm $ 5.3
0.171220.071 $ \\pm $ 0.967.04 $ \\pm $ 5.060.49 $ \\pm $ 5.72
0.8173-0.078 $ \\pm $ 0.988.17 $ \\pm $ 6.92-1.81 $ \\pm $ 8.10 $ * $
2187-0.22 $ \\pm $ 0.947.19 $ \\pm $ 4.52-1.72 $ \\pm $ 6.66
4182-0.59 $ \\pm $ 0.99 $ \\# $8.79 $ \\pm $ 5.77 $ * $-3.66 $ \\pm $ 7.34 $ \\# $
6184-0.94 $ \\pm $ 0.83 $ \\# $13.74 $ \\pm $ 8.80 $ \\# $-10.85 $ \\pm $ 9.74 $ \\# $
10 $ \\ast\\ast $53-0.95 $ \\pm $ 0.9823.54 $ \\pm $ 11.03-17.59 $ \\pm $ 15.35
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See Table 1 for representative sine( $ \\varphi $), speed and directed velocity data. Data from one slide of cells performed at 10 V/cm is also provided. Net displacement graphs for 0, 2, 4 and 6 V/cm are presented in polar plots depicted in Fig. 4. In a subset of cells, examination of the cell migration distance during each 10 minute interval over the two hour experiment revealed a relatively uniform migration speed. 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See Table 1 for representative sine( $ \\varphi $), speed and directed velocity data. Data from one slide of cells performed at 10 V/cm is also provided. Net displacement graphs for 0, 2, 4 and 6 V/cm are presented in polar plots depicted in Fig. 4. In a subset of cells, examination of the cell migration distance during each 10 minute interval over the two hour experiment revealed a relatively uniform migration speed. This finding indicates that there is no apparent latency time before initiation of field-induced migration as was reported for fibroblasts [10].", "bbox": [617, 372, 1106, 560], "page_width": 1224, "page_height": 1584}, "marker_signature": {"type": "none", "raw_marker": null, "number": null, "kind": "generic_text", "normalized_text": "no-field control for fields >0.8 V/cm and was dose-dependent for field strengths >4 V/cm. See Table 1 for representative sine( $ \\varphi $), speed and directed velocity data. Data from one slide of cells performed at 10 V/cm is also provided. Net displacement graphs for 0, 2, 4 and 6 V/cm are presented in polar plots depicted in Fig. 4. In a subset of cells, examination of the cell migration distance during each 10 minute interval over the two hour experiment revealed a relatively uniform migration speed. This finding indicates that there is no apparent latency time before initiation of field-induced migration as was reported for fibroblasts [10]."}, "layout_signature": {"width": 489, "width_bucket": 500, "height": 188, "left": 617, "top": 372, "right": 1106, "bottom": 560, "x_center": 861.5, "x_center_bucket": 850, "y_center": 466.0, "x_ratio": 0.7038, "y_ratio": 0.2942, "width_ratio": 0.3995, "height_ratio": 0.1187, "line_count": 1}, "span_signature": {"font_size": 8.98, "font_size_median": 8.98, "font_size_bucket": 9.0, "font_family_norm": "Times-Roman", "bold": false, "italic": true, "span_count": 148}, "_in_visual_container": null, "_container_bbox": null, "_container_text": null, "_text_source": null, "_ocr_raw_status": null, "_ocr_raw_error_type": null, "render_default": true, "index_default": true, "zone": "body_zone", "style_family": "body_like", "style_family_authority": "body_zone_with_anchor", "reading_band_id": "band_040", "display_cluster_candidate_id": "", "layout_region": "reference_candidate", "boundary_before": "weak", "boundary_after": "none", "bridge_eligible": false, "insert_score": {"score": 0.15, "decision": "body", "evidence": ["narrow_width"]}, "role_verification_status": "ACCEPT", "role_source": "non_structural_normalized_role", "role_evidence": ["pre-gate normalized non-structural role preserved"]} +{"paper_id": "28JLIHLS", "page": 3, "block_id": 14, "raw_label": "text", "raw_order": 6, "bbox": [617, 566, 1108, 791], "text": "Inhibitor Studies. Treatment with U-73122 significantly decreased chondrocyte cathodal migration to electric field of 6 V/cm, see Fig. 5(a). The directed velocity for the vehicle, DMSO, field group was $ -12.42 \\pm 15.50 $ $ \\mu $m/h (109 cells) and $ -0.004 \\pm 5.11 $ $ \\mu $m/h (147 cells) for the no-field control, respectively (p < 0.0001). In contrast, cells treated with U-73122 subjected to an applied electric field exhibited a significant directed velocity of $ -1.81 \\pm 7.23 $ $ \\mu $m/h (306 cells) versus $ 0.60 \\pm 5.48 $ $ \\mu $m/h (n = 200) for the no-field, U-73122 control cells, p < 0.0001. No differences existed between the DMSO and U-73122 no-field controls (p = 0.52). 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Treatment with U-73122 significantly decreased chondrocyte cathodal migration to electric field of 6 V/cm, see Fig. 5(a). The directed velocity for the vehicle, DMSO, field group was $ -12.42 \\pm 15.50 $ $ \\mu $m/h (109 cells) and $ -0.004 \\pm 5.11 $ $ \\mu $m/h (147 cells) for the no-field control, respectively (p < 0.0001). In contrast, cells treated with U-73122 subjected to an applied electric field exhibited a significant directed velocity of $ -1.81 \\pm 7.23 $ $ \\mu $m/h (306 cells) versus $ 0.60 \\pm 5.48 $ $ \\mu $m/h (n = 200) for the no-field, U-73122 control cells, p < 0.0001. No differences existed between the DMSO and U-73122 no-field controls (p = 0.52). DMSO and control medium applied field groups", "bbox": [617, 566, 1108, 791], "page_width": 1224, "page_height": 1584}, "marker_signature": {"type": "none", "raw_marker": null, "number": null, "kind": "generic_text", "normalized_text": "Inhibitor Studies. Treatment with U-73122 significantly decreased chondrocyte cathodal migration to electric field of 6 V/cm, see Fig. 5(a). The directed velocity for the vehicle, DMSO, field group was $ -12.42 \\pm 15.50 $ $ \\mu $m/h (109 cells) and $ -0.004 \\pm 5.11 $ $ \\mu $m/h (147 cells) for the no-field control, respectively (p < 0.0001). In contrast, cells treated with U-73122 subjected to an applied electric field exhibited a significant directed velocity of $ -1.81 \\pm 7.23 $ $ \\mu $m/h (306 cells) versus $ 0.60 \\pm 5.48 $ $ \\mu $m/h (n = 200) for the no-field, U-73122 control cells, p < 0.0001. No differences existed between the DMSO and U-73122 no-field controls (p = 0.52). DMSO and control medium applied field groups"}, "layout_signature": {"width": 491, "width_bucket": 500, "height": 225, "left": 617, "top": 566, "right": 1108, "bottom": 791, "x_center": 862.5, "x_center_bucket": 850, "y_center": 678.5, "x_ratio": 0.7047, "y_ratio": 0.4283, "width_ratio": 0.4011, "height_ratio": 0.142, "line_count": 1}, "span_signature": {"font_size": 8.98, "font_size_median": 8.98, "font_size_bucket": 9.0, "font_family_norm": "Times-Bold", "bold": true, "italic": true, "span_count": 160}, "_in_visual_container": null, "_container_bbox": null, "_container_text": null, "_text_source": null, "_ocr_raw_status": null, "_ocr_raw_error_type": null, "render_default": true, "index_default": true, "zone": "body_zone", "style_family": "body_like", "style_family_authority": "body_zone_with_anchor", "reading_band_id": "band_040", "display_cluster_candidate_id": "", "layout_region": "reference_candidate", "boundary_before": "weak", "boundary_after": "none", "bridge_eligible": false, "insert_score": {"score": 0.15, "decision": "body", "evidence": ["narrow_width"]}, "role_verification_status": "ACCEPT", "role_source": "non_structural_normalized_role", "role_evidence": ["pre-gate normalized non-structural role preserved"]} +{"paper_id": "28JLIHLS", "page": 3, "block_id": 15, "raw_label": "image", "raw_order": null, "bbox": [637, 824, 1088, 1304], "text": "", "page_width": 1224, "page_height": 1584, "role": "figure_asset", "role_confidence": 0.85, "evidence": ["media label: image"], "seed_role": "media_asset", "seed_confidence": 0.85, "seed_evidence": ["media label: image"], "span_metadata": null, "raw_observation": {"block_id": 15, "page": 3, "raw_label": "image", "text": "", "bbox": [637, 824, 1088, 1304], "page_width": 1224, "page_height": 1584}, "marker_signature": {"type": "empty", "raw_marker": null, "number": null, "kind": null, "normalized_text": ""}, "layout_signature": {"width": 451, "width_bucket": 450, "height": 480, "left": 637, "top": 824, "right": 1088, "bottom": 1304, "x_center": 862.5, "x_center_bucket": 850, "y_center": 1064.0, "x_ratio": 0.7047, "y_ratio": 0.6717, "width_ratio": 0.3685, "height_ratio": 0.303, "line_count": 1}, "span_signature": {"font_size": null, "font_size_median": null, "font_size_bucket": null, "font_family_norm": null, "bold": false, "italic": false, "span_count": 0}, "_in_visual_container": null, "_container_bbox": null, "_container_text": null, "_text_source": null, "_ocr_raw_status": null, "_ocr_raw_error_type": null, "render_default": true, "index_default": true, "zone": "body_zone", "style_family": "unknown_like", "style_family_authority": "fallback", "reading_band_id": "band_040", "display_cluster_candidate_id": "", "layout_region": "reference_candidate", "boundary_before": "weak", "boundary_after": "none", "bridge_eligible": false, "insert_score": {"score": 0.15, "decision": "body", "evidence": ["narrow_width"]}, "role_verification_status": "ACCEPT", "role_source": "non_structural_normalized_role", "role_evidence": ["pre-gate normalized non-structural role preserved"], "asset_family_hint": "figure_like", "asset_family_confidence": 0.7, "asset_family_evidence": ["raw_label:image"]} +{"paper_id": "28JLIHLS", "page": 3, "block_id": 16, "raw_label": "figure_title", "raw_order": null, "bbox": [617, 1319, 1107, 1468], "text": "Fig. 4 Net displacement graphs of chondrocytes after one hour for applied field strengths of 0, 2, 4 and 6 V/cm. The conducting solution was serum supplemented DMEM and studies were performed at ~37°C. The radial axes are in microns, n = number of cells, + and - indicate the anode and cathode, respectively. Each open circle represents a single cell. A cell, which does not move during the hour, remains in the center of the polar plot, i.e., (0 μm, 0 deg).", "page_width": 1224, "page_height": 1584, "role": "figure_caption", "role_confidence": 0.92, "evidence": ["figure_title label: Fig. 4 Net displacement graphs of chondrocytes after one hou"], "seed_role": "figure_caption", "seed_confidence": 0.92, "seed_evidence": ["figure_title label: Fig. 4 Net displacement graphs of chondrocytes after one hou"], "span_metadata": [{"size": 7.98199987411499, "font": "Helvetica-Bold", "flags": 16, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 7.98199987411499, "font": "Helvetica-Bold", "flags": 16, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 7.98199987411499, "font": "Helvetica-Bold", "flags": 16, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 7.98199987411499, "font": "Helvetica-Bold", "flags": 16, "color": 0, "dir": [1.0, 0.0], "wmode": 0}, {"size": 7.98199987411499, "font": "Helvetica-Bold", "flags": 16, "color": 0, "dir": 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The conducting solution was serum supplemented DMEM and studies were performed at ~37°C. The radial axes are in microns, n = number of cells, + and - indicate the anode and cathode, respectively. Each open circle represents a single cell. A cell, which does not move during the hour, remains in the center of the polar plot, i.e., (0 μm, 0 deg).", "bbox": [617, 1319, 1107, 1468], "page_width": 1224, "page_height": 1584}, "marker_signature": {"type": "figure_number", "raw_marker": "Fig. 4", "number": 4, "kind": "figure", "normalized_text": "Fig. 4 Net displacement graphs of chondrocytes after one hour for applied field strengths of 0, 2, 4 and 6 V/cm. The conducting solution was serum supplemented DMEM and studies were performed at ~37°C. The radial axes are in microns, n = number of cells, + and - indicate the anode and cathode, respectively. Each open circle represents a single cell. 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"flags": 16, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 7.98199987411499, "font": "Helvetica-Bold", "flags": 16, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 7.98199987411499, "font": "Helvetica-Bold", "flags": 16, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 7.98199987411499, "font": "Helvetica-Bold", "flags": 16, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 7.98199987411499, "font": "Helvetica-Bold", "flags": 16, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}], "raw_observation": {"block_id": 3, "page": 4, "raw_label": "figure_title", "text": "Fig. 5 Effect of inositol phospholipid pathway inhibitors on chondrocyte motility. (a) Directed velocity of chondrocytes after exposure to U-73122 or vehicle (DMSO). * indicates p < 0.0001 relative to the vehicle no-field group and ** indicates p < 0.0001 relative to both the applied-field vehicle group and U-73122 no-field group. (b) Directed velocity of chondrocytes after exposure to neomycin and control media (i.e., serum supplemented DMEM). * indicates p < 0.0001 relative to the neomycin no-field group and ** indicates p < 0.0001 with respect to the applied-field control medium group and p = 0.03 with respect to the neomycin no-field group. The number in the parentheses indicates the number of cells studied.", "bbox": [115, 710, 606, 933], "page_width": 1224, "page_height": 1584}, "marker_signature": {"type": "figure_number", "raw_marker": "Fig. 5", "number": 5, "kind": "figure", "normalized_text": "Fig. 5 Effect of inositol phospholipid pathway inhibitors on chondrocyte motility. (a) Directed velocity of chondrocytes after exposure to U-73122 or vehicle (DMSO). * indicates p < 0.0001 relative to the vehicle no-field group and ** indicates p < 0.0001 relative to both the applied-field vehicle group and U-73122 no-field group. (b) Directed velocity of chondrocytes after exposure to neomycin and control media (i.e., serum supplemented DMEM). * indicates p < 0.0001 relative to the neomycin no-field group and ** indicates p < 0.0001 with respect to the applied-field control medium group and p = 0.03 with respect to the neomycin no-field group. The number in the parentheses indicates the number of cells studied."}, "layout_signature": {"width": 491, "width_bucket": 500, "height": 223, "left": 115, "top": 710, "right": 606, "bottom": 933, "x_center": 360.5, "x_center_bucket": 350, "y_center": 821.5, "x_ratio": 0.2945, "y_ratio": 0.5186, "width_ratio": 0.4011, "height_ratio": 0.1408, "line_count": 1}, "span_signature": {"font_size": 7.99, "font_size_median": 7.98, "font_size_bucket": 8.0, "font_family_norm": "Helvetica-Bold", "bold": true, "italic": true, "span_count": 174}, "_in_visual_container": null, "_container_bbox": null, "_container_text": null, "_text_source": null, "_ocr_raw_status": null, "_ocr_raw_error_type": null, "render_default": true, "index_default": true, "zone": "display_zone", "style_family": "legend_like", "style_family_authority": "figure_marker", "reading_band_id": "band_039", "display_cluster_candidate_id": "", "layout_region": "reference_candidate", "boundary_before": "weak", "boundary_after": "none", "bridge_eligible": false, "insert_score": {"score": 0.15, "decision": "body", "evidence": ["narrow_width"]}, "role_verification_status": "ACCEPT", "role_source": "accepted_figure_caption_artifact", "role_evidence": ["figure caption matched accepted figure artifact"]} +{"paper_id": "28JLIHLS", "page": 4, "block_id": 4, "raw_label": "text", "raw_order": 1, "bbox": [114, 975, 604, 1197], "text": "were also not different (p = 0.13). Under the influence of an applied field neomycin appears to promote anodal migration, see Fig. 5(b). The directed velocity for the neomycin applied field group, $ 1.29 \\pm 6.61 $ (n = 165 cells) derived from a sine( $ \\varphi $) of 0.50 ± 0.99, was significantly different than that for the no-field group, $ -0.28 \\pm 3.37 $ $ \\mu $m/h (181 cells) derived from a sine( $ \\varphi $) of $ -0.008 \\pm 0.99 $, p < 0.0001. In contrast, control applied field cells exhibited a directed velocity of $ -8.53 \\pm 8.51 $ $ \\mu $m/h (104 cells) and $ 1.34 \\pm 5.84 $ $ \\mu $m/h (n = 118) for the no-field group (p < 0.0001). No differences existed between the neomycin and control medium no-field groups (p = 0.13).", "page_width": 1224, "page_height": 1584, "role": "body_paragraph", "role_confidence": 0.6, "evidence": ["default body_paragraph for text label"], "seed_role": "body_paragraph", "seed_confidence": 0.6, "seed_evidence": ["default body_paragraph for text label"], "span_metadata": [{"size": 8.979999542236328, "font": "Times-Roman", "flags": 4, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 8.979999542236328, "font": "Times-Roman", "flags": 4, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 8.979999542236328, "font": "Times-Roman", "flags": 4, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 8.979999542236328, "font": "Times-Roman", "flags": 4, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 8.979999542236328, "font": "Times-Roman", "flags": 4, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 8.979999542236328, "font": "Times-Roman", "flags": 4, 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Under the influence of an applied field neomycin appears to promote anodal migration, see Fig. 5(b). The directed velocity for the neomycin applied field group, $ 1.29 \\pm 6.61 $ (n = 165 cells) derived from a sine( $ \\varphi $) of 0.50 ± 0.99, was significantly different than that for the no-field group, $ -0.28 \\pm 3.37 $ $ \\mu $m/h (181 cells) derived from a sine( $ \\varphi $) of $ -0.008 \\pm 0.99 $, p < 0.0001. In contrast, control applied field cells exhibited a directed velocity of $ -8.53 \\pm 8.51 $ $ \\mu $m/h (104 cells) and $ 1.34 \\pm 5.84 $ $ \\mu $m/h (n = 118) for the no-field group (p < 0.0001). No differences existed between the neomycin and control medium no-field groups (p = 0.13).", "bbox": [114, 975, 604, 1197], "page_width": 1224, "page_height": 1584}, "marker_signature": {"type": "none", "raw_marker": null, "number": null, "kind": "generic_text", "normalized_text": "were also not different (p = 0.13). Under the influence of an applied field neomycin appears to promote anodal migration, see Fig. 5(b). The directed velocity for the neomycin applied field group, $ 1.29 \\pm 6.61 $ (n = 165 cells) derived from a sine( $ \\varphi $) of 0.50 ± 0.99, was significantly different than that for the no-field group, $ -0.28 \\pm 3.37 $ $ \\mu $m/h (181 cells) derived from a sine( $ \\varphi $) of $ -0.008 \\pm 0.99 $, p < 0.0001. In contrast, control applied field cells exhibited a directed velocity of $ -8.53 \\pm 8.51 $ $ \\mu $m/h (104 cells) and $ 1.34 \\pm 5.84 $ $ \\mu $m/h (n = 118) for the no-field group (p < 0.0001). No differences existed between the neomycin and control medium no-field groups (p = 0.13)."}, "layout_signature": {"width": 490, "width_bucket": 500, "height": 222, "left": 114, "top": 975, "right": 604, "bottom": 1197, "x_center": 359.0, "x_center_bucket": 350, "y_center": 1086.0, "x_ratio": 0.2933, "y_ratio": 0.6856, "width_ratio": 0.4003, "height_ratio": 0.1402, "line_count": 1}, "span_signature": {"font_size": 8.98, "font_size_median": 8.98, "font_size_bucket": 9.0, "font_family_norm": "Times-Roman", "bold": false, "italic": true, "span_count": 182}, "_in_visual_container": null, "_container_bbox": null, "_container_text": null, "_text_source": null, "_ocr_raw_status": null, "_ocr_raw_error_type": null, "render_default": true, "index_default": true, "zone": "body_zone", "style_family": "body_like", "style_family_authority": "body_zone_with_anchor", "reading_band_id": "band_039", "display_cluster_candidate_id": "", "layout_region": "reference_candidate", "boundary_before": "weak", "boundary_after": "none", "bridge_eligible": false, "insert_score": {"score": 0.15, "decision": "body", "evidence": ["narrow_width"]}, "role_verification_status": "ACCEPT", "role_source": "non_structural_normalized_role", "role_evidence": ["pre-gate normalized non-structural role preserved"]} +{"paper_id": "28JLIHLS", "page": 4, "block_id": 5, "raw_label": "text", "raw_order": 2, "bbox": [114, 1205, 604, 1467], "text": "Serum-Free Studies. Cathodally directed migration was also observed in serum-free studies, see Fig. 6. The directed velocity for 6 V/cm applied in the absence of serum was $ -3.63 \\pm 6.82 $ $ \\mu $m/h (n=176 cells) versus $ 0.46 \\pm 5.19 $ $ \\mu $m/h (n=125 cells) for the no-field group (p<0.0001). In contrast, the directed velocity for the control serum groups was $ -10.85 \\pm 9.74 $ $ \\mu $m/h (n=184 cells) and $ 0.95 \\pm 5.30 $ $ \\mu $m/h (n=108 cells) for the applied field and no-field control groups, respectively (p<0.0001). Clearly, the presence of serum enhanced the directed velocity nearly three-fold. Interestingly, the migration speed (or motility) of cells in the serum-free studies was nearly identical for both, despite the presence or absence of the applied field. The disparity in directed velocity stems from the fact that the sine( $ \\varphi $) value was", "page_width": 1224, "page_height": 1584, "role": "body_paragraph", "role_confidence": 0.6, "evidence": ["default body_paragraph for text label"], "seed_role": "body_paragraph", "seed_confidence": 0.6, "seed_evidence": ["default body_paragraph for text label"], "span_metadata": [{"size": 8.979999542236328, "font": "Times-Bold", "flags": 20, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 8.979999542236328, "font": "Times-Bold", "flags": 20, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 8.979999542236328, "font": "Times-Bold", "flags": 20, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 8.979999542236328, "font": "Times-Roman", "flags": 4, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 8.979999542236328, "font": "Times-Roman", "flags": 4, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 8.979999542236328, "font": "Times-Roman", "flags": 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Cathodally directed migration was also observed in serum-free studies, see Fig. 6. The directed velocity for 6 V/cm applied in the absence of serum was $ -3.63 \\pm 6.82 $ $ \\mu $m/h (n=176 cells) versus $ 0.46 \\pm 5.19 $ $ \\mu $m/h (n=125 cells) for the no-field group (p<0.0001). In contrast, the directed velocity for the control serum groups was $ -10.85 \\pm 9.74 $ $ \\mu $m/h (n=184 cells) and $ 0.95 \\pm 5.30 $ $ \\mu $m/h (n=108 cells) for the applied field and no-field control groups, respectively (p<0.0001). Clearly, the presence of serum enhanced the directed velocity nearly three-fold. Interestingly, the migration speed (or motility) of cells in the serum-free studies was nearly identical for both, despite the presence or absence of the applied field. The disparity in directed velocity stems from the fact that the sine( $ \\varphi $) value was", "bbox": [114, 1205, 604, 1467], "page_width": 1224, "page_height": 1584}, "marker_signature": {"type": "none", "raw_marker": null, "number": null, "kind": "generic_text", "normalized_text": "Serum-Free Studies. Cathodally directed migration was also observed in serum-free studies, see Fig. 6. The directed velocity for 6 V/cm applied in the absence of serum was $ -3.63 \\pm 6.82 $ $ \\mu $m/h (n=176 cells) versus $ 0.46 \\pm 5.19 $ $ \\mu $m/h (n=125 cells) for the no-field group (p<0.0001). In contrast, the directed velocity for the control serum groups was $ -10.85 \\pm 9.74 $ $ \\mu $m/h (n=184 cells) and $ 0.95 \\pm 5.30 $ $ \\mu $m/h (n=108 cells) for the applied field and no-field control groups, respectively (p<0.0001). Clearly, the presence of serum enhanced the directed velocity nearly three-fold. Interestingly, the migration speed (or motility) of cells in the serum-free studies was nearly identical for both, despite the presence or absence of the applied field. The disparity in directed velocity stems from the fact that the sine( $ \\varphi $) value was"}, "layout_signature": {"width": 490, "width_bucket": 500, "height": 262, "left": 114, "top": 1205, "right": 604, "bottom": 1467, "x_center": 359.0, "x_center_bucket": 350, "y_center": 1336.0, "x_ratio": 0.2933, "y_ratio": 0.8434, "width_ratio": 0.4003, "height_ratio": 0.1654, "line_count": 1}, "span_signature": {"font_size": 8.98, "font_size_median": 8.98, "font_size_bucket": 9.0, "font_family_norm": "Times-Bold", "bold": true, "italic": true, "span_count": 217}, "_in_visual_container": null, "_container_bbox": null, "_container_text": null, "_text_source": null, "_ocr_raw_status": null, "_ocr_raw_error_type": null, "render_default": true, "index_default": true, "zone": "body_zone", "style_family": "body_like", "style_family_authority": "body_family_anchor", "reading_band_id": "band_039", "display_cluster_candidate_id": "", "layout_region": "reference_candidate", "boundary_before": "weak", "boundary_after": "none", "bridge_eligible": false, "insert_score": {"score": 0.15, "decision": "body", "evidence": ["narrow_width"]}, "role_verification_status": "ACCEPT", "role_source": "non_structural_normalized_role", "role_evidence": ["pre-gate normalized non-structural role preserved"]} +{"paper_id": "28JLIHLS", "page": 4, "block_id": 6, "raw_label": "image", "raw_order": null, "bbox": [622, 68, 1104, 331], "text": "", "page_width": 1224, "page_height": 1584, "role": "figure_asset", "role_confidence": 0.85, "evidence": ["media label: image"], "seed_role": "media_asset", "seed_confidence": 0.85, "seed_evidence": ["media label: image"], "span_metadata": null, "raw_observation": {"block_id": 6, "page": 4, "raw_label": "image", "text": "", "bbox": [622, 68, 1104, 331], "page_width": 1224, "page_height": 1584}, "marker_signature": {"type": "empty", "raw_marker": null, "number": null, "kind": null, "normalized_text": ""}, "layout_signature": {"width": 482, "width_bucket": 475, "height": 263, "left": 622, "top": 68, "right": 1104, "bottom": 331, "x_center": 863.0, "x_center_bucket": 875, "y_center": 199.5, "x_ratio": 0.7051, "y_ratio": 0.1259, "width_ratio": 0.3938, "height_ratio": 0.166, "line_count": 1}, "span_signature": {"font_size": null, "font_size_median": null, "font_size_bucket": null, "font_family_norm": null, "bold": false, "italic": false, "span_count": 0}, "_in_visual_container": null, "_container_bbox": null, "_container_text": null, "_text_source": null, "_ocr_raw_status": null, "_ocr_raw_error_type": null, "render_default": true, "index_default": true, "zone": "body_zone", "style_family": "unknown_like", "style_family_authority": "fallback", "reading_band_id": "band_039", "display_cluster_candidate_id": "", "layout_region": "reference_candidate", "boundary_before": "weak", "boundary_after": "none", "bridge_eligible": false, "insert_score": {"score": 0.15, "decision": "body", "evidence": ["narrow_width"]}, "role_verification_status": "ACCEPT", "role_source": "non_structural_normalized_role", "role_evidence": ["pre-gate normalized non-structural role preserved"], "asset_family_hint": "figure_like", "asset_family_confidence": 0.7, "asset_family_evidence": ["raw_label:image"]} +{"paper_id": "28JLIHLS", "page": 4, "block_id": 7, "raw_label": "figure_title", "raw_order": null, "bbox": [616, 346, 1106, 479], "text": "Fig. 6 Net displacement graph of chondrocytes in studies performed using 6 V/cm for one hour in serum-free DMEM at $ \\sim37^{\\circ} $C. 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(a) Directed cathodal migration was observed in the applied-field group. (b) No-field applied cells exhibited random migration. The radial axes of the polar plots are in microns, n = number of cells, + and - indicate the anode and cathode, respectively. Each open circle represents a single cell.", "bbox": [616, 346, 1106, 479], "page_width": 1224, "page_height": 1584}, "marker_signature": {"type": "figure_number", "raw_marker": "Fig. 6", "number": 6, "kind": "figure", "normalized_text": "Fig. 6 Net displacement graph of chondrocytes in studies performed using 6 V/cm for one hour in serum-free DMEM at $ \\sim37^{\\circ} $C. (a) Directed cathodal migration was observed in the applied-field group. (b) No-field applied cells exhibited random migration. The radial axes of the polar plots are in microns, n = number of cells, + and - indicate the anode and cathode, respectively. 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0.437±0.99 (p<0.0001)."}, "layout_signature": {"width": 487, "width_bucket": 475, "height": 61, "left": 618, "top": 516, "right": 1105, "bottom": 577, "x_center": 861.5, "x_center_bucket": 850, "y_center": 546.5, "x_ratio": 0.7038, "y_ratio": 0.345, "width_ratio": 0.3979, "height_ratio": 0.0385, "line_count": 1}, "span_signature": {"font_size": 8.98, "font_size_median": 8.98, "font_size_bucket": 9.0, "font_family_norm": "MathematicalPi-One", "bold": false, "italic": true, "span_count": 41}, "_in_visual_container": null, "_container_bbox": null, "_container_text": null, "_text_source": null, "_ocr_raw_status": null, "_ocr_raw_error_type": null, "render_default": true, "index_default": true, "zone": "body_zone", "style_family": "body_like", "style_family_authority": "body_zone_with_anchor", "reading_band_id": "band_039", "display_cluster_candidate_id": "", "layout_region": "reference_candidate", "boundary_before": "weak", "boundary_after": "none", "bridge_eligible": false, "insert_score": {"score": 0.15, "decision": "body", "evidence": ["narrow_width"]}, "role_verification_status": "ACCEPT", "role_source": "non_structural_normalized_role", "role_evidence": ["pre-gate normalized non-structural role preserved"]} +{"paper_id": "28JLIHLS", "page": 4, "block_id": 9, "raw_label": "text", "raw_order": 4, "bbox": [614, 591, 1110, 834], "text": "Temperature Studies. Significant cathodic migration was observed at room temperature and at $ \\sim37^{\\circ} $C (p<0.0001 for both), with cells moving nearly twofold faster at physiologic temperatures, see Fig. 7. The directed velocity for cells at room temperature was $ -5.70\\pm5.70 $ $ \\mu $m/h (n=158 cells) and $ -0.25\\pm2.86 $ $ \\mu $m/h (n=87 cells) for the 6 V/cm applied field group and 0 V/cm group, respectively (p<0.0001). The directed velocity for cells at physiologic temperature was $ -11.57\\pm10.91 $ $ \\mu $m/h (n=91 cells) and $ 1.02\\pm5.94 $ $ \\mu $m/h (n=83 cells) for the 6 V/cm applied field group and 0 V/cm group, respectively (p<0.0001). 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Significant cathodic migration was observed at room temperature and at $ \\sim37^{\\circ} $C (p<0.0001 for both), with cells moving nearly twofold faster at physiologic temperatures, see Fig. 7. The directed velocity for cells at room temperature was $ -5.70\\pm5.70 $ $ \\mu $m/h (n=158 cells) and $ -0.25\\pm2.86 $ $ \\mu $m/h (n=87 cells) for the 6 V/cm applied field group and 0 V/cm group, respectively (p<0.0001). The directed velocity for cells at physiologic temperature was $ -11.57\\pm10.91 $ $ \\mu $m/h (n=91 cells) and $ 1.02\\pm5.94 $ $ \\mu $m/h (n=83 cells) for the 6 V/cm applied field group and 0 V/cm group, respectively (p<0.0001). The directed velocity of the no-field groups at both temperatures was similar (p=0.23).", "bbox": [614, 591, 1110, 834], "page_width": 1224, "page_height": 1584}, "marker_signature": {"type": "none", "raw_marker": null, "number": null, "kind": "generic_text", "normalized_text": "Temperature Studies. Significant cathodic migration was observed at room temperature and at $ \\sim37^{\\circ} $C (p<0.0001 for both), with cells moving nearly twofold faster at physiologic temperatures, see Fig. 7. The directed velocity for cells at room temperature was $ -5.70\\pm5.70 $ $ \\mu $m/h (n=158 cells) and $ -0.25\\pm2.86 $ $ \\mu $m/h (n=87 cells) for the 6 V/cm applied field group and 0 V/cm group, respectively (p<0.0001). The directed velocity for cells at physiologic temperature was $ -11.57\\pm10.91 $ $ \\mu $m/h (n=91 cells) and $ 1.02\\pm5.94 $ $ \\mu $m/h (n=83 cells) for the 6 V/cm applied field group and 0 V/cm group, respectively (p<0.0001). The directed velocity of the no-field groups at both temperatures was similar (p=0.23)."}, "layout_signature": {"width": 496, "width_bucket": 500, "height": 243, "left": 614, "top": 591, "right": 1110, "bottom": 834, "x_center": 862.0, "x_center_bucket": 850, "y_center": 712.5, "x_ratio": 0.7042, "y_ratio": 0.4498, "width_ratio": 0.4052, "height_ratio": 0.1534, "line_count": 1}, "span_signature": {"font_size": 8.98, "font_size_median": 8.98, "font_size_bucket": 9.0, "font_family_norm": "Times-Bold", "bold": true, "italic": true, "span_count": 197}, "_in_visual_container": null, "_container_bbox": null, "_container_text": null, "_text_source": null, "_ocr_raw_status": null, "_ocr_raw_error_type": null, "render_default": true, "index_default": true, "zone": "body_zone", "style_family": "body_like", "style_family_authority": "body_zone_with_anchor", "reading_band_id": "band_039", "display_cluster_candidate_id": "", "layout_region": "reference_candidate", "boundary_before": "weak", "boundary_after": "none", "bridge_eligible": false, "insert_score": {"score": 0.15, "decision": "body", "evidence": ["narrow_width"]}, "role_verification_status": "ACCEPT", "role_source": "non_structural_normalized_role", "role_evidence": ["pre-gate normalized non-structural role preserved"]} +{"paper_id": "28JLIHLS", "page": 4, "block_id": 10, "raw_label": "paragraph_title", "raw_order": 5, "bbox": [620, 844, 718, 867], "text": "Discussion", "page_width": 1224, "page_height": 1584, "role": "section_heading", "role_confidence": 0.9, "evidence": ["explicit scholarly heading: Discussion"], "seed_role": "section_heading", "seed_confidence": 0.9, "seed_evidence": ["explicit scholarly heading: Discussion"], "span_metadata": [{"size": 9.977999687194824, "font": "Times-Bold", "flags": 20, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}], "raw_observation": {"block_id": 10, "page": 4, "raw_label": "paragraph_title", "text": "Discussion", "bbox": [620, 844, 718, 867], "page_width": 1224, "page_height": 1584}, "marker_signature": {"type": "canonical_section_name", "raw_marker": "Discussion", "number": null, "kind": "heading", "normalized_text": "Discussion"}, "layout_signature": {"width": 98, "width_bucket": 100, "height": 23, "left": 620, "top": 844, "right": 718, "bottom": 867, "x_center": 669.0, "x_center_bucket": 675, "y_center": 855.5, "x_ratio": 0.5466, "y_ratio": 0.5401, "width_ratio": 0.0801, "height_ratio": 0.0145, "line_count": 1}, "span_signature": {"font_size": 9.98, "font_size_median": 9.98, "font_size_bucket": 10.0, "font_family_norm": "Times-Bold", "bold": true, "italic": true, "span_count": 1}, "_in_visual_container": null, "_container_bbox": null, "_container_text": null, "_text_source": null, "_ocr_raw_status": null, "_ocr_raw_error_type": null, "render_default": true, "index_default": true, "zone": "body_zone", "style_family": "heading_like", "style_family_authority": "heading_marker", "reading_band_id": "band_040", "display_cluster_candidate_id": "", "layout_region": "reference_candidate", "boundary_before": "weak", "boundary_after": "none", "bridge_eligible": false, "insert_score": {"score": 0.15, "decision": "body", "evidence": ["narrow_width"]}, "role_verification_status": "ACCEPT", "role_source": "accepted_heading", "role_evidence": ["heading verified by heading artifact"]} +{"paper_id": "28JLIHLS", "page": 4, "block_id": 11, "raw_label": "text", "raw_order": 6, "bbox": [617, 873, 1107, 997], "text": "In the present investigation, we report for the first time that cultured chondrocytes exhibit cathodal migration under field strengths demonstrated previously to elicit galvanotaxis in other cell types. 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Cells responded with cathodal migration to field strengths as low as 0.8 V/cm and displayed dose-dependent cathodal migration for field strengths greater than 4 V/cm. The", "bbox": [617, 873, 1107, 997], "page_width": 1224, "page_height": 1584}, "marker_signature": {"type": "none", "raw_marker": null, "number": null, "kind": "generic_text", "normalized_text": "In the present investigation, we report for the first time that cultured chondrocytes exhibit cathodal migration under field strengths demonstrated previously to elicit galvanotaxis in other cell types. Cells responded with cathodal migration to field strengths as low as 0.8 V/cm and displayed dose-dependent cathodal migration for field strengths greater than 4 V/cm. 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Cell migration at ~37°C was enhanced twofold over similar studies conducted at room temperature. * indicates $ p<0.0001 $ relative to ~37°C no-field group and ** indicates $ p<0.0001 $ with respect to both the ~37°C applied-field group and the ~25°C no-field group. The number in the parentheses indicates the number of cells studied.", "page_width": 1224, "page_height": 1584, "role": "figure_caption", "role_confidence": 0.92, "evidence": ["figure_title label: Fig. 7 Effect of temperature on chondrocyte motility. Cell m"], "seed_role": "figure_caption", "seed_confidence": 0.92, "seed_evidence": ["figure_title label: Fig. 7 Effect of temperature on chondrocyte motility. 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Cell migration at ~37°C was enhanced twofold over similar studies conducted at room temperature. * indicates $ p<0.0001 $ relative to ~37°C no-field group and ** indicates $ p<0.0001 $ with respect to both the ~37°C applied-field group and the ~25°C no-field group. The number in the parentheses indicates the number of cells studied.", "bbox": [618, 1335, 1108, 1467], "page_width": 1224, "page_height": 1584}, "marker_signature": {"type": "figure_number", "raw_marker": "Fig. 7", "number": 7, "kind": "figure", "normalized_text": "Fig. 7 Effect of temperature on chondrocyte motility. Cell migration at ~37°C was enhanced twofold over similar studies conducted at room temperature. * indicates $ p<0.0001 $ relative to ~37°C no-field group and ** indicates $ p<0.0001 $ with respect to both the ~37°C applied-field group and the ~25°C no-field group. 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presence of serum during field application. Cell migration appears to be an active process with extension of cytoplasmic processes in the direction of movement. As reported for other cell types, some chondrocytes exhibited perpendicular alignment when subjected to an applied DC electric field for greater than an hour. Antagonists of the inositol phospholipid pathway inhibited directed migration. Results from this study may be applicable to cartilage healing/repair and tissue engineering. Several potential parameters have been identified which can be manipulated to optimize chondrocyte migration.", "bbox": [114, 69, 604, 300], "page_width": 1224, "page_height": 1584}, "marker_signature": {"type": "none", "raw_marker": null, "number": null, "kind": "generic_text", "normalized_text": "observations were not found to be dependent on the presence of serum during field application. Cell migration appears to be an active process with extension of cytoplasmic processes in the direction of movement. As reported for other cell types, some chondrocytes exhibited perpendicular alignment when subjected to an applied DC electric field for greater than an hour. Antagonists of the inositol phospholipid pathway inhibited directed migration. Results from this study may be applicable to cartilage healing/repair and tissue engineering. Several potential parameters have been identified which can be manipulated to optimize chondrocyte migration."}, "layout_signature": {"width": 490, "width_bucket": 500, "height": 231, "left": 114, "top": 69, "right": 604, "bottom": 300, "x_center": 359.0, "x_center_bucket": 350, "y_center": 184.5, "x_ratio": 0.2933, "y_ratio": 0.1165, "width_ratio": 0.4003, "height_ratio": 0.1458, "line_count": 1}, "span_signature": {"font_size": 8.98, "font_size_median": 8.98, "font_size_bucket": 9.0, "font_family_norm": "Times-Roman", "bold": false, "italic": true, "span_count": 145}, "_in_visual_container": null, "_container_bbox": null, "_container_text": null, "_text_source": null, "_ocr_raw_status": null, "_ocr_raw_error_type": null, "render_default": true, "index_default": true, "zone": "body_zone", "style_family": "body_like", "style_family_authority": "body_zone_with_anchor", "insert_score": {"score": 0.15, "decision": "body", "evidence": ["narrow_width"]}, "role_verification_status": "ACCEPT", "role_source": "non_structural_normalized_role", "role_evidence": ["pre-gate normalized non-structural role preserved"]} +{"paper_id": "28JLIHLS", "page": 5, "block_id": 1, "raw_label": "text", "raw_order": 2, "bbox": [115, 301, 604, 761], "text": "An understanding of the mechanisms of galvanotropism and galvanotaxis may depend on the relative role of forces generated by electro-osmosis and electrophoresis [18,20]. The relatively few cells that became detached from the substrate floated toward the anode, a consequence of electrophoresis and the negative cell surface potential. Under the conditions of the present investigation, electro-osmotic fluid flow is directed from the anode to cathode due to the negative surface potential of the cells and the glass chamber walls [16,21–23]. Electro-osmosis may be responsible for redistribution of cell surface receptors toward the cathodal face of the cell, leading perhaps to cathodal directed migration or perpendicular alignment (e.g., [24–26]). Alternatively, lateral mobility of cell proteins and receptors may be related to the fact that current goes around the cell (rather than through) due to the high impedance of the cell membrane (e.g., [24,27–29]). Current densities of similar magnitudes to those reported here were used by Garcia et al. [30] to investigate the role of fluid flow convection in the nutrient transport of cartilage. Redistribution of integrins (e.g., fibronectin [38]), cell surface receptors that mediate cell–extracellular matrix and cell–cell interactions [31,32], may have implications on tissue remodeling, repair and regeneration [2,3,14,33,34].", "page_width": 1224, "page_height": 1584, "role": "body_paragraph", "role_confidence": 0.6, "evidence": ["default body_paragraph for text label"], "seed_role": "body_paragraph", "seed_confidence": 0.6, "seed_evidence": ["default body_paragraph for text label"], "span_metadata": [{"size": 8.979999542236328, "font": "Times-Roman", "flags": 4, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 8.979999542236328, "font": "Times-Roman", "flags": 4, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 8.979999542236328, "font": "Times-Roman", "flags": 4, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 8.979999542236328, "font": "Times-Roman", "flags": 4, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 8.979999542236328, 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The relatively few cells that became detached from the substrate floated toward the anode, a consequence of electrophoresis and the negative cell surface potential. Under the conditions of the present investigation, electro-osmotic fluid flow is directed from the anode to cathode due to the negative surface potential of the cells and the glass chamber walls [16,21–23]. Electro-osmosis may be responsible for redistribution of cell surface receptors toward the cathodal face of the cell, leading perhaps to cathodal directed migration or perpendicular alignment (e.g., [24–26]). Alternatively, lateral mobility of cell proteins and receptors may be related to the fact that current goes around the cell (rather than through) due to the high impedance of the cell membrane (e.g., [24,27–29]). Current densities of similar magnitudes to those reported here were used by Garcia et al. [30] to investigate the role of fluid flow convection in the nutrient transport of cartilage. Redistribution of integrins (e.g., fibronectin [38]), cell surface receptors that mediate cell–extracellular matrix and cell–cell interactions [31,32], may have implications on tissue remodeling, repair and regeneration [2,3,14,33,34].", "bbox": [115, 301, 604, 761], "page_width": 1224, "page_height": 1584}, "marker_signature": {"type": "none", "raw_marker": null, "number": null, "kind": "generic_text", "normalized_text": "An understanding of the mechanisms of galvanotropism and galvanotaxis may depend on the relative role of forces generated by electro-osmosis and electrophoresis [18,20]. The relatively few cells that became detached from the substrate floated toward the anode, a consequence of electrophoresis and the negative cell surface potential. Under the conditions of the present investigation, electro-osmotic fluid flow is directed from the anode to cathode due to the negative surface potential of the cells and the glass chamber walls [16,21–23]. Electro-osmosis may be responsible for redistribution of cell surface receptors toward the cathodal face of the cell, leading perhaps to cathodal directed migration or perpendicular alignment (e.g., [24–26]). Alternatively, lateral mobility of cell proteins and receptors may be related to the fact that current goes around the cell (rather than through) due to the high impedance of the cell membrane (e.g., [24,27–29]). Current densities of similar magnitudes to those reported here were used by Garcia et al. [30] to investigate the role of fluid flow convection in the nutrient transport of cartilage. Redistribution of integrins (e.g., fibronectin [38]), cell surface receptors that mediate cell–extracellular matrix and cell–cell interactions [31,32], may have implications on tissue remodeling, repair and regeneration [2,3,14,33,34]."}, "layout_signature": {"width": 489, "width_bucket": 500, "height": 460, "left": 115, "top": 301, "right": 604, "bottom": 761, "x_center": 359.5, "x_center_bucket": 350, "y_center": 531.0, "x_ratio": 0.2937, "y_ratio": 0.3352, "width_ratio": 0.3995, "height_ratio": 0.2904, "line_count": 1}, "span_signature": {"font_size": 8.98, "font_size_median": 8.98, "font_size_bucket": 9.0, "font_family_norm": "Times-Roman", "bold": false, "italic": true, "span_count": 304}, "_in_visual_container": null, "_container_bbox": null, "_container_text": null, "_text_source": null, "_ocr_raw_status": null, "_ocr_raw_error_type": null, "render_default": true, "index_default": true, "zone": "body_zone", "style_family": "body_like", "style_family_authority": "body_zone_with_anchor", "reading_band_id": "band_039", "display_cluster_candidate_id": "", "layout_region": "reference_candidate", "boundary_before": "weak", "boundary_after": "none", "bridge_eligible": false, "insert_score": {"score": 0.15, "decision": "body", "evidence": ["narrow_width"]}, "role_verification_status": "ACCEPT", "role_source": "non_structural_normalized_role", "role_evidence": ["pre-gate normalized non-structural role preserved"]} +{"paper_id": "28JLIHLS", "page": 5, "block_id": 2, "raw_label": "text", "raw_order": 3, "bbox": [114, 761, 604, 1176], "text": "Our observation that chondrocytes align perpendicular to the direction of the applied electric field is reminiscent of studies where cells align perpendicularly with respect to applied mechanical load to their 2D plating substrate [6,7,35,36]. Interestingly, the orientation behavior of cells are different when strained in three-dimensional matrices [37] and to fluid shear in two dimensions [6,38,39], aligning their principal axis with the direction of principal matrix strain and fluid flow respectively. The applied electric field in the present study may therefore impose a force on the cell having similar attributes to those developed under certain types of mechanical loading. The alignment of chondrocytes to fluid flow [39] has been observed using significantly greater fluid rates than those generated by electro-osmosis in the present study, which are estimated to be $ \\sim1-15 $ $ \\mu $m/s (in the direction of the cathode). Cells have been suggested, as in the case of substrate stretching studies, to minimize the strain or stress gradient by aligning their long axis perpendicular to the principal direction of stretch. In a similar manner, the cell elongation and perpendicular alignment observed in the current study may be indicative of a mechanism to minimize the electric field gradient across the cell [40].", "page_width": 1224, "page_height": 1584, "role": "body_paragraph", "role_confidence": 0.6, "evidence": ["default body_paragraph for text label"], "seed_role": "body_paragraph", "seed_confidence": 0.6, "seed_evidence": ["default body_paragraph for text label"], "span_metadata": [{"size": 8.979999542236328, "font": "Times-Roman", "flags": 4, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 8.979999542236328, "font": "Times-Roman", "flags": 4, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 8.979999542236328, "font": "Times-Roman", "flags": 4, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 8.979999542236328, "font": "Times-Roman", "flags": 4, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 8.979999542236328, "font": "Times-Roman", "flags": 4, "color": 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0.0], "wmode": 0}, {"size": 8.979999542236328, "font": "Times-Roman", "flags": 4, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}], "raw_observation": {"block_id": 2, "page": 5, "raw_label": "text", "text": "Our observation that chondrocytes align perpendicular to the direction of the applied electric field is reminiscent of studies where cells align perpendicularly with respect to applied mechanical load to their 2D plating substrate [6,7,35,36]. Interestingly, the orientation behavior of cells are different when strained in three-dimensional matrices [37] and to fluid shear in two dimensions [6,38,39], aligning their principal axis with the direction of principal matrix strain and fluid flow respectively. The applied electric field in the present study may therefore impose a force on the cell having similar attributes to those developed under certain types of mechanical loading. The alignment of chondrocytes to fluid flow [39] has been observed using significantly greater fluid rates than those generated by electro-osmosis in the present study, which are estimated to be $ \\sim1-15 $ $ \\mu $m/s (in the direction of the cathode). Cells have been suggested, as in the case of substrate stretching studies, to minimize the strain or stress gradient by aligning their long axis perpendicular to the principal direction of stretch. In a similar manner, the cell elongation and perpendicular alignment observed in the current study may be indicative of a mechanism to minimize the electric field gradient across the cell [40].", "bbox": [114, 761, 604, 1176], "page_width": 1224, "page_height": 1584}, "marker_signature": {"type": "none", "raw_marker": null, "number": null, "kind": "generic_text", "normalized_text": "Our observation that chondrocytes align perpendicular to the direction of the applied electric field is reminiscent of studies where cells align perpendicularly with respect to applied mechanical load to their 2D plating substrate [6,7,35,36]. Interestingly, the orientation behavior of cells are different when strained in three-dimensional matrices [37] and to fluid shear in two dimensions [6,38,39], aligning their principal axis with the direction of principal matrix strain and fluid flow respectively. The applied electric field in the present study may therefore impose a force on the cell having similar attributes to those developed under certain types of mechanical loading. The alignment of chondrocytes to fluid flow [39] has been observed using significantly greater fluid rates than those generated by electro-osmosis in the present study, which are estimated to be $ \\sim1-15 $ $ \\mu $m/s (in the direction of the cathode). Cells have been suggested, as in the case of substrate stretching studies, to minimize the strain or stress gradient by aligning their long axis perpendicular to the principal direction of stretch. In a similar manner, the cell elongation and perpendicular alignment observed in the current study may be indicative of a mechanism to minimize the electric field gradient across the cell [40]."}, "layout_signature": {"width": 490, "width_bucket": 500, "height": 415, "left": 114, "top": 761, "right": 604, "bottom": 1176, "x_center": 359.0, "x_center_bucket": 350, "y_center": 968.5, "x_ratio": 0.2933, "y_ratio": 0.6114, "width_ratio": 0.4003, "height_ratio": 0.262, "line_count": 1}, "span_signature": {"font_size": 8.98, "font_size_median": 8.98, "font_size_bucket": 9.0, "font_family_norm": "Times-Roman", "bold": false, "italic": true, "span_count": 268}, "_in_visual_container": null, "_container_bbox": null, "_container_text": null, "_text_source": null, "_ocr_raw_status": null, "_ocr_raw_error_type": null, "render_default": true, "index_default": true, "zone": "body_zone", "style_family": "body_like", "style_family_authority": "body_zone_with_anchor", "reading_band_id": "band_039", "display_cluster_candidate_id": "", "layout_region": "reference_candidate", "boundary_before": "weak", "boundary_after": "none", "bridge_eligible": false, "insert_score": {"score": 0.15, "decision": "body", "evidence": ["narrow_width"]}, "role_verification_status": "ACCEPT", "role_source": "non_structural_normalized_role", "role_evidence": ["pre-gate normalized non-structural role preserved"]} +{"paper_id": "28JLIHLS", "page": 5, "block_id": 3, "raw_label": "text", "raw_order": 4, "bbox": [114, 1175, 604, 1468], "text": "Calcium and related biochemical messengers have been implicated as mediators of galvanotaxis and in chemotaxis (e.g., [26,41–43]). Germane to the present study, Frenkel and co-workers [3] have demonstrated that nitric oxide inhibits chondrocyte adhesion to fibronectin thereby decreasing chemotaxis to BMP [3]. Our findings that U-73122 and neomycin were able to inhibit chondrocyte galvanotaxis are consistent with a role by inositol phospholipid metabolism. It should be noted that neomycin is highly positively charged and, in addition to inhibiting the inositol phospholipid pathway, decreases membrane surface potential [18,44]. It is well established that cell surface potential can be manipulated with surface treatments and cations [45,46]. As discussed above, a change of the cell surface potential will vary the electro-osmotic force acting on the cell as well as the nature of receptor redistribution on the cell surface. 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"28JLIHLS", "page": 5, "block_id": 5, "raw_label": "text", "raw_order": 6, "bbox": [617, 130, 1107, 659], "text": "Cells subjected to 0 V/cm in the absence of serum also exhibited significant cathodal migration relative to no-field controls, albeit significantly slower than in the presence of serum. This finding indicates that cathodal directedness is not serum-dependent whereas migration speed can be modulated by serum. The insensitivity of cathodal directed migration to serum argues strongly against the role of gradients of serum products in establishing the chondrocyte galvanotaxis response (i.e., chemotaxis). The mechanism by which serum enhances chondrocyte directed cathodal speed remains to be investigated. Our findings are similar to those of Fang and co-workers [43], who reported that directional migration of human keratinocytes depends on growth factors, where in the absence of growth factors, the cell migration rate decreased but directionality was maintained. In view of reports in the literature that agonists heighten the response of certain cell types undergoing mechanical stimulation [47–49], we cannot dismiss the possibility that chemical stimuli may act synergistically with the electric field to increase directed velocity. Moreover, the activation of integrin and growth factor receptors, such as epidermal growth factor, may be required for the response [29,32,50]. Interestingly, serum appears to be required for cathodal migration in certain cell types. For example, the removal of serum eliminated the galvanotaxis response in corneal epithelial cells that was restored when epidermal growth factor or other selected growth factors/cytokines were added to serum-free medium [51].", "page_width": 1224, "page_height": 1584, "role": "body_paragraph", "role_confidence": 0.6, "evidence": ["default body_paragraph for text label"], "seed_role": "body_paragraph", "seed_confidence": 0.6, "seed_evidence": ["default body_paragraph for text label"], "span_metadata": [{"size": 8.979999542236328, "font": "Times-Roman", "flags": 4, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 8.979999542236328, "font": "Times-Roman", "flags": 4, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 8.979999542236328, "font": "Times-Roman", "flags": 4, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 8.979999542236328, "font": "Times-Roman", "flags": 4, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 8.979999542236328, "font": 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"flags": 4, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 8.979999542236328, "font": "Universal-GreekwithMathP", "flags": 4, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 8.979999542236328, "font": "Times-Roman", "flags": 4, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 8.979999542236328, "font": "Universal-GreekwithMathP", "flags": 4, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 8.979999542236328, "font": "Times-Roman", "flags": 4, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}], "raw_observation": {"block_id": 5, "page": 5, "raw_label": "text", "text": "Cells subjected to 0 V/cm in the absence of serum also exhibited significant cathodal migration relative to no-field controls, albeit significantly slower than in the presence of serum. This finding indicates that cathodal directedness is not serum-dependent whereas migration speed can be modulated by serum. The insensitivity of cathodal directed migration to serum argues strongly against the role of gradients of serum products in establishing the chondrocyte galvanotaxis response (i.e., chemotaxis). The mechanism by which serum enhances chondrocyte directed cathodal speed remains to be investigated. Our findings are similar to those of Fang and co-workers [43], who reported that directional migration of human keratinocytes depends on growth factors, where in the absence of growth factors, the cell migration rate decreased but directionality was maintained. In view of reports in the literature that agonists heighten the response of certain cell types undergoing mechanical stimulation [47–49], we cannot dismiss the possibility that chemical stimuli may act synergistically with the electric field to increase directed velocity. Moreover, the activation of integrin and growth factor receptors, such as epidermal growth factor, may be required for the response [29,32,50]. Interestingly, serum appears to be required for cathodal migration in certain cell types. For example, the removal of serum eliminated the galvanotaxis response in corneal epithelial cells that was restored when epidermal growth factor or other selected growth factors/cytokines were added to serum-free medium [51].", "bbox": [617, 130, 1107, 659], "page_width": 1224, "page_height": 1584}, "marker_signature": {"type": "none", "raw_marker": null, "number": null, "kind": "generic_text", "normalized_text": "Cells subjected to 0 V/cm in the absence of serum also exhibited significant cathodal migration relative to no-field controls, albeit significantly slower than in the presence of serum. This finding indicates that cathodal directedness is not serum-dependent whereas migration speed can be modulated by serum. The insensitivity of cathodal directed migration to serum argues strongly against the role of gradients of serum products in establishing the chondrocyte galvanotaxis response (i.e., chemotaxis). The mechanism by which serum enhances chondrocyte directed cathodal speed remains to be investigated. Our findings are similar to those of Fang and co-workers [43], who reported that directional migration of human keratinocytes depends on growth factors, where in the absence of growth factors, the cell migration rate decreased but directionality was maintained. In view of reports in the literature that agonists heighten the response of certain cell types undergoing mechanical stimulation [47–49], we cannot dismiss the possibility that chemical stimuli may act synergistically with the electric field to increase directed velocity. Moreover, the activation of integrin and growth factor receptors, such as epidermal growth factor, may be required for the response [29,32,50]. Interestingly, serum appears to be required for cathodal migration in certain cell types. For example, the removal of serum eliminated the galvanotaxis response in corneal epithelial cells that was restored when epidermal growth factor or other selected growth factors/cytokines were added to serum-free medium [51]."}, "layout_signature": {"width": 490, "width_bucket": 500, "height": 529, "left": 617, "top": 130, "right": 1107, "bottom": 659, "x_center": 862.0, "x_center_bucket": 850, "y_center": 394.5, "x_ratio": 0.7042, "y_ratio": 0.2491, "width_ratio": 0.4003, "height_ratio": 0.334, "line_count": 1}, "span_signature": {"font_size": 8.98, "font_size_median": 8.98, "font_size_bucket": 9.0, "font_family_norm": "Times-Roman", "bold": false, "italic": true, "span_count": 404}, "_in_visual_container": null, "_container_bbox": null, "_container_text": null, "_text_source": null, "_ocr_raw_status": null, "_ocr_raw_error_type": null, "render_default": true, "index_default": true, "zone": "body_zone", "style_family": "body_like", "style_family_authority": "body_zone_with_anchor", "reading_band_id": "band_039", "display_cluster_candidate_id": "", "layout_region": "reference_candidate", "boundary_before": "weak", "boundary_after": "none", "bridge_eligible": false, "insert_score": {"score": 0.15, "decision": "body", "evidence": ["narrow_width"]}, "role_verification_status": "ACCEPT", "role_source": "non_structural_normalized_role", "role_evidence": ["pre-gate normalized non-structural role preserved"]} +{"paper_id": "28JLIHLS", "page": 5, "block_id": 6, "raw_label": "text", "raw_order": 7, "bbox": [617, 658, 1107, 981], "text": "Since the migration behavior of chondrocytes at room and physiologic temperatures were similar, it does not appear that the temperature elevation causes a nonspecific increase in cell motility. On the contrary, temperature appears to potentiate the specific mechanisms that govern directed cell migration. The role of cell attachment (e.g., $ [52–55] $) and its sensitivity on temperature $ [56] $ may also contribute to the observations of electric field-induced migration. The effect of Joule heating, a quantity that is proportional to the magnitude of the applied current, was investigated by further increasing the chamber resistance by decreasing the spacer thickness between the parallel plates. The channel area reduction permitted the application of a minimized current to generate the desired field strength in the chamber. No effect of Joule heating was observed in our studies, which may be attributed to the high resistance associated with the chamber and rapid heat dissipation between the two large parallel glass surfaces containing the cells.", "page_width": 1224, "page_height": 1584, "role": "body_paragraph", "role_confidence": 0.6, "evidence": ["default body_paragraph for text label"], "seed_role": "body_paragraph", "seed_confidence": 0.6, "seed_evidence": ["default body_paragraph for text label"], "span_metadata": [{"size": 8.979999542236328, "font": "Times-Roman", "flags": 4, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 8.979999542236328, "font": "Times-Roman", "flags": 4, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 8.979999542236328, "font": "Times-Roman", "flags": 4, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 8.979999542236328, "font": "Times-Roman", "flags": 4, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 8.979999542236328, "font": 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On the contrary, temperature appears to potentiate the specific mechanisms that govern directed cell migration. The role of cell attachment (e.g., $ [52–55] $) and its sensitivity on temperature $ [56] $ may also contribute to the observations of electric field-induced migration. The effect of Joule heating, a quantity that is proportional to the magnitude of the applied current, was investigated by further increasing the chamber resistance by decreasing the spacer thickness between the parallel plates. The channel area reduction permitted the application of a minimized current to generate the desired field strength in the chamber. No effect of Joule heating was observed in our studies, which may be attributed to the high resistance associated with the chamber and rapid heat dissipation between the two large parallel glass surfaces containing the cells.", "bbox": [617, 658, 1107, 981], "page_width": 1224, "page_height": 1584}, "marker_signature": {"type": "none", "raw_marker": null, "number": null, "kind": "generic_text", "normalized_text": "Since the migration behavior of chondrocytes at room and physiologic temperatures were similar, it does not appear that the temperature elevation causes a nonspecific increase in cell motility. On the contrary, temperature appears to potentiate the specific mechanisms that govern directed cell migration. The role of cell attachment (e.g., $ [52–55] $) and its sensitivity on temperature $ [56] $ may also contribute to the observations of electric field-induced migration. The effect of Joule heating, a quantity that is proportional to the magnitude of the applied current, was investigated by further increasing the chamber resistance by decreasing the spacer thickness between the parallel plates. The channel area reduction permitted the application of a minimized current to generate the desired field strength in the chamber. No effect of Joule heating was observed in our studies, which may be attributed to the high resistance associated with the chamber and rapid heat dissipation between the two large parallel glass surfaces containing the cells."}, "layout_signature": {"width": 490, "width_bucket": 500, "height": 323, "left": 617, "top": 658, "right": 1107, "bottom": 981, "x_center": 862.0, "x_center_bucket": 850, "y_center": 819.5, "x_ratio": 0.7042, "y_ratio": 0.5174, "width_ratio": 0.4003, "height_ratio": 0.2039, "line_count": 1}, "span_signature": {"font_size": 8.98, "font_size_median": 8.98, "font_size_bucket": 9.0, "font_family_norm": "Times-Roman", "bold": false, "italic": true, "span_count": 251}, "_in_visual_container": null, "_container_bbox": null, "_container_text": null, "_text_source": null, "_ocr_raw_status": null, "_ocr_raw_error_type": null, "render_default": true, "index_default": true, "zone": "body_zone", "style_family": "body_like", "style_family_authority": "body_zone_with_anchor", "reading_band_id": "band_039", "display_cluster_candidate_id": "", "layout_region": "reference_candidate", "boundary_before": "weak", "boundary_after": "none", "bridge_eligible": false, "insert_score": {"score": 0.15, "decision": "body", "evidence": ["narrow_width"]}, "role_verification_status": "ACCEPT", "role_source": "non_structural_normalized_role", "role_evidence": ["pre-gate normalized non-structural role preserved"]} +{"paper_id": "28JLIHLS", "page": 5, "block_id": 7, "raw_label": "text", "raw_order": 8, "bbox": [616, 980, 1107, 1468], "text": "As cartilage experiences deformation during joint loading, chondrocytes may see electric fields associated with streaming potentials estimated to be up to 15 V/cm, with current densities of up to 0.1 A/cm² [57]. Coincidentally, these field strengths are on the same order that we observed chondrocyte directed migration in the present study. Guided primarily by the galvanotaxis literature (e.g., [8–12]), the intent of this investigation was not to reproduce the electrokinetic environment of the chondrocyte but rather to develop a research tool that permits reproducible study and characterization of chondrocyte migration. With this caveat, it is interesting to note that electric fields are clinically used for tissue healing in the field of orthopaedics (e.g., [58–61]). Studies have indicated that direct current application via implantable electrodes stimulates mitosis and recruitment of osteogenic cells [62]. If current levels are optimal, such responses are enhanced with respect to the natural healing process. In vitro support of these migration effects include the observation that osteoblasts and osteoclasts migrate to different poles under an applied electric field [8,63]. In view of the fact that electric fields have already been adopted as a clinical modality in orthopaedics, it is reasonable to suggest that the phenomena of electric field-induced chondrocyte migration may be developed to provide enhanced cartilage healing in vivo. Furthermore, applications in vitro, such as the active seeding of scaffolds, are conceivable as well.", "page_width": 1224, "page_height": 1584, "role": "body_paragraph", "role_confidence": 0.6, "evidence": ["default body_paragraph for text label"], "seed_role": "body_paragraph", "seed_confidence": 0.6, "seed_evidence": ["default body_paragraph for text label"], "span_metadata": [{"size": 8.979999542236328, "font": "Times-Roman", "flags": 4, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 8.979999542236328, "font": "Times-Roman", "flags": 4, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 8.979999542236328, "font": "Times-Roman", "flags": 4, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 8.979999542236328, "font": "Times-Roman", "flags": 4, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 8.979999542236328, "font": "Times-Roman", "flags": 4, "color": 2301728, "dir": [1.0, 0.0], "wmode": 0}, {"size": 8.979999542236328, "font": "Times-Roman", 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Coincidentally, these field strengths are on the same order that we observed chondrocyte directed migration in the present study. Guided primarily by the galvanotaxis literature (e.g., [8–12]), the intent of this investigation was not to reproduce the electrokinetic environment of the chondrocyte but rather to develop a research tool that permits reproducible study and characterization of chondrocyte migration. With this caveat, it is interesting to note that electric fields are clinically used for tissue healing in the field of orthopaedics (e.g., [58–61]). Studies have indicated that direct current application via implantable electrodes stimulates mitosis and recruitment of osteogenic cells [62]. If current levels are optimal, such responses are enhanced with respect to the natural healing process. In vitro support of these migration effects include the observation that osteoblasts and osteoclasts migrate to different poles under an applied electric field [8,63]. In view of the fact that electric fields have already been adopted as a clinical modality in orthopaedics, it is reasonable to suggest that the phenomena of electric field-induced chondrocyte migration may be developed to provide enhanced cartilage healing in vivo. Furthermore, applications in vitro, such as the active seeding of scaffolds, are conceivable as well.", "bbox": [616, 980, 1107, 1468], "page_width": 1224, "page_height": 1584}, "marker_signature": {"type": "none", "raw_marker": null, "number": null, "kind": "generic_text", "normalized_text": "As cartilage experiences deformation during joint loading, chondrocytes may see electric fields associated with streaming potentials estimated to be up to 15 V/cm, with current densities of up to 0.1 A/cm² [57]. Coincidentally, these field strengths are on the same order that we observed chondrocyte directed migration in the present study. Guided primarily by the galvanotaxis literature (e.g., [8–12]), the intent of this investigation was not to reproduce the electrokinetic environment of the chondrocyte but rather to develop a research tool that permits reproducible study and characterization of chondrocyte migration. With this caveat, it is interesting to note that electric fields are clinically used for tissue healing in the field of orthopaedics (e.g., [58–61]). Studies have indicated that direct current application via implantable electrodes stimulates mitosis and recruitment of osteogenic cells [62]. If current levels are optimal, such responses are enhanced with respect to the natural healing process. In vitro support of these migration effects include the observation that osteoblasts and osteoclasts migrate to different poles under an applied electric field [8,63]. In view of the fact that electric fields have already been adopted as a clinical modality in orthopaedics, it is reasonable to suggest that the phenomena of electric field-induced chondrocyte migration may be developed to provide enhanced cartilage healing in vivo. 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Using bright field or fluorescence microscopy (not used in this study), the galvanotaxis chamber permits real-time observation and tracking of cell migration cultured on a substrate and in a chemical environment defined by the investigator. Future studies will elucidate the role of integrins and the cell cytoskeleton involved in chondrocyte cathodal directed migration [3,68]. Understanding of the mechanisms underlying chondrocyte galvanotaxis and electric field-induced reorientation may lead to the development of strategies to direct chondrocyte movement for cartilage repair and tissue engineering applications.", "bbox": [115, 69, 604, 313], "page_width": 1224, "page_height": 1584}, "marker_signature": {"type": "none", "raw_marker": null, "number": null, "kind": "generic_text", "normalized_text": "The galvanotaxis system adopted in the present study offers a method to investigate cell migration in individual cells as well as cell populations (e.g., [62–67]). Using bright field or fluorescence microscopy (not used in this study), the galvanotaxis chamber permits real-time observation and tracking of cell migration cultured on a substrate and in a chemical environment defined by the investigator. Future studies will elucidate the role of integrins and the cell cytoskeleton involved in chondrocyte cathodal directed migration [3,68]. 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"role_verification_status": "ACCEPT", "role_source": "non_structural_normalized_role", "role_evidence": ["pre-gate normalized non-structural role preserved"]} diff --git a/tests/test_ocr_figure_vnext_real_papers.py b/tests/test_ocr_figure_vnext_real_papers.py index 92cb4dda..5866f62f 100644 --- a/tests/test_ocr_figure_vnext_real_papers.py +++ b/tests/test_ocr_figure_vnext_real_papers.py @@ -34,3 +34,25 @@ def test_real_paper_special_fallbacks_reports_diff_shape(): assert "vnext_matched_count" in diff assert "legacy_consumed_block_ids" in diff assert "vnext_consumed_block_ids" in diff + + +def test_real_paper_sidecar_reports_diff_shape(): + blocks_path = Path("tests/fixtures/ocr_vnext_real_papers/28JLIHLS/blocks.structured.jsonl") + diff = compare_blocks_file(blocks_path) + + assert diff["paper"] == "28JLIHLS" + assert "legacy_matched_count" in diff + assert "vnext_matched_count" in diff + assert "legacy_consumed_block_ids" in diff + assert "vnext_consumed_block_ids" in diff + + +def test_real_paper_dense_composite_reports_diff_shape(): + blocks_path = Path("tests/fixtures/ocr_vnext_real_papers/24YKLTHQ/blocks.structured.jsonl") + diff = compare_blocks_file(blocks_path) + + assert diff["paper"] == "24YKLTHQ" + assert "legacy_matched_count" in diff + assert "vnext_matched_count" in diff + assert "legacy_consumed_block_ids" in diff + assert "vnext_consumed_block_ids" in diff