Assessing a n Novel Synthetic FZD4 Agonist to Rescue Blood Brain Barrier Ddysfunction
Bibliographic record
Abstract
The Blood Brain Barrier (BBB) is a selective structure controlling the passage of molecules between the blood and the brain. It is characterized by the formation of tight junctions between endothelial cells (ECs). The Wnt/β-catenin signalling pathway controls angiogenesis and barrier integrity, both crucial for vascular development and homeostasis of the BBB. FZD4 is required for angiogenesis and barrier functions in brain vasculature, forming a receptor complex with WNT7/GPR124/RECK/LRP5/6 to evoke Wnt-mediated signalling in brain vasculature. Our lab has engineered novel synthetic antibody-based Frizzled/LRP Agonists mimicking Wnt ligands. This thesis investigated activation of the FZD4 receptor complexes using F4L6 and its efficiency to promote CNS barrier function and promote recovery in stroke animal models. A GPR124 siRNA knockdown in ECs was established showing F4L6 acts independently of GPR124. Weassessed F4L6 in an endothelin-1 induced ischemic stroke model and showed decreased leakageat day 10 post-stroke and significant behavioural rescue.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".