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Wide binaries with hot subdwarf-B (sdB) primaries and main sequence companions are thought to form only through stable Roche-lobe overflow (RLOF) of the sdB progenitor near the tip of the red giant branch (RGB). We present the orbital parameters of 11 new long-period composite sdB binaries based on spectroscopic observations obtained with the UVES, FEROS, and CHIRON spectrographs. Using all wide sdB binaries with known orbital parameters, 23 systems, the observed period distribution is found to match very well with theoretical predictions. A second result is the strong correlation between the orbital period (P) and the mass ratio (q) in the observed wide sdB binaries. In the P-q plane two distinct groups emerge, with the main group (18 systems) showing a strong correlation of lower mass ratios at longer orbital periods. The second group comprises systems that are thought to be formed from higher mass progenitors. Based on theoretical models, a correlation between the initial mass ratio at the start of RLOF and core mass of the sdB progenitor is found, which defines a mass-ratio range at which RLOF is stable on the RGB.
Cerebral cavernous malformations (CCMs) are vascular lesions in the central nervous system causing strokes and seizures which currently can only be treated through neurosurgery. The disease arises through changes in the regulatory networks of endothelial cells that must be comprehensively understood to develop alternative, non-invasive pharmacological therapies. Here, we present the results of several unbiased small-molecule suppression screens in which we applied a total of 5,268 unique substances to CCM mutant worm, zebrafish, mouse, or human endothelial cells. We used a systems biology-based target prediction tool to integrate the results with the whole-transcriptome profile of zebrafish CCM2 mutants, revealing signaling pathways relevant to the disease and potential targets for small-molecule-based therapies. We found indirubin-3-monoxime to alleviate the lesion burden in murine preclinical models of CCM2 and CCM3 and suppress the loss-of-CCM phenotypes in human endothelial cells. Our multi-organism-based approach reveals new components of the CCM regulatory network and foreshadows novel small-molecule-based therapeutic applications for suppressing this devastating disease in patients.