An essential process for cilia formation during epithelialization is the movement of the centrosome to dock with the cell′s nascent apical membrane. Our study examined centrosome positioning during the development of Danio rerio′s left-right organizer (Kupffer′s Vesicle, KV). We found that when KV mesenchymal-like cells transition into epithelial cells that are organizing into a rosette-like structure, KV cells move their centrosomes from random intracellular positions to the forming apical membrane in a Rab11 and Rab35 dependent manner. During this process, centrosomes construct cilia intracellularly that associated with Myo-Va while the centrosomes repositioned towards the rosette center. Once the centrosomes with associated cilia reach the rosette center, the intracellular cilia recruit Arl13b until they extend into the forming lumen. This process begins when the lumen reaches an area of approximately 300 μm2. Using optogenetic and depletion strategies, we identified that the small GTPases, Rab11 and Rab35, regulate not only cilia formation, but lumenogenesis, whereas Rab8 was primarily involved in regulating cilia length. These studies substantiate both conserved and unique roles for Rab11, Rab35, and Rab8 function in cilia formation during lumenogenesis.
An essential process during Danio rerio’s left-right organizer (Kupffer’s Vesicle, KV) formation is the formation of a motile cilium by developing KV cells which extends into the KV lumen. Beating of motile cilia within the KV lumen directs fluid flow to establish the embryo’s left-right axis. However, the timepoint at which KV cells start to form cilia and how cilia formation is coordinated with KV lumen formation have not been examined. We identified that nascent KV cells form cilia at their centrosomes at random intracellular positions that then move towards a forming apical membrane containing cystic fibrosis transmembrane conductance regulator (CFTR). Using optogenetic clustering approaches, we found that Rab35 positive membranes recruit Rab11 to modulate CFTR delivery to the apical membrane, which is required for lumen opening, and subsequent cilia extension into the lumen. Once the intracellular cilia reach the CFTR positive apical membrane, Arl13b-positive cilia extend and elongate in a Rab8 dependent manner into the forming lumen once the lumen reaches an area of 300 μm2. These studies demonstrate the need to acutely coordinate Rab8, Rab11, and Rab35-mediated membrane trafficking events to ensure appropriate timing in lumen and cilia formation during KV development.
Criminal recidivism models are tools that have gained widespread adoption by parole boards across the United States to assist with parole decisions. These models take in large amounts of data about an individual and then predict whether an individual would commit a crime if released on parole. Although such models are not the only or primary factor in making the final parole decision, questions have been raised about their accuracy, fairness, and interpretability. In this paper, various machine learning-based criminal recidivism models are created based on a real-world parole decision dataset from the state of Georgia in the United States. The recidivism models are comparatively evaluated for their accuracy, fairness, and interpretability. It is found that there are noted differences and trade-offs between accuracy, fairness, and being inherently interpretable. Therefore, choosing the best model depends on the desired balance between accuracy, fairness, and interpretability, as no model is perfect or consistently the best across different criteria.
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