Cerebral organoids provide unparalleled access to human brain development in vitro. However, variability induced by current culture methodologies precludes using organoids as robust disease models. To address this, we developed an automated Organoid Culture and Assay (ORCA) system to support longitudinal unbiased phenotyping of organoids at scale across multiple patient lines. We then characterized organoid variability using novel machine learning methods and found that the contribution of donor, clone, and batch is significant and remarkably consistent over gene expression, morphology, and cell-type composition. Next, we performed multi-factorial protocol optimization, producing a directed forebrain protocol compatible with 96-well culture that exhibits low variability while preserving tissue complexity. Finally, we used ORCA to study tuberous sclerosis, a disease with known genetics but poorly representative animal models. For the first time, we report highly reproducible early morphological and molecular signatures of disease in heterozygous TSC+/− forebrain organoids, demonstrating the benefit of a scaled organoid system for phenotype discovery in human disease models.
Baseline Near Detector time projection chamber is unique in the design of its charge readout planes. These anode plane assemblies (APAs) have been fabricated and assembled to meet strict accuracy and precision requirements: wire spacing of 3 mm ± 0.5 mm and wire tension of 7 N ± 1 N across 3,964 wires per APA, and flatness within 0.5 mm over the 4 m × 2.5 m extent of each APA. This paper describes the design, manufacture and assembly of these key detector components, with a focus on the quality assurance at each stage.
K: Detector design and construction technologies and materials; Neutrino detectors; Time projection chambers; Noble liquid detectors (scintillation, ionization, double-phase)
In the case described anatomically corrected transposition of the great vessels is associated with situs inversus. Anatomically corrected transposition is extremely rare, and has not been previously reported with situs inversus. This type of transposition should not be confused with classical corrected transposition. Thus the case examined exhibited a D-bulboventricular loop with L-transposition and atrial inversion, so that blood flow was physiologically incorrect as in classical complete transposition. In the case examined, it was also found that bulbar musculature was present between the aorta and the mitral valve.Additional study of the conducting tissue revealed inversion of the sinoatrial node with the atria, and also of the atrial portion of the atrioventricular node. The atrioventricular bundle and its branches were in expected positions in relation to a large ventricular septal defect. These results are discussed with regard to previous reports and to the embryology of the conducting tissue.Additional
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