Pancreatic cancer is the most lethal common solid malignancy. Systemic therapies are often ineffective, and predictive biomarkers to guide treatment are urgently needed. We generated a pancreatic cancer patient-derived organoid (PDO) library that recapitulates the mutational spectrum and transcriptional subtypes of primary pancreatic cancer. New driver oncogenes were nominated and transcriptomic analyses revealed unique clusters. PDOs exhibited heterogeneous responses to standard-of-care chemotherapeutics and investigational agents. In a case study manner, we found that PDO therapeutic profiles paralleled patient outcomes and that PDOs enabled longitudinal assessment of chemosensitivity and evaluation of synchronous metastases. We derived organoid-based gene expression signatures of chemosensitivity that predicted improved responses for many patients to chemotherapy in both the adjuvant and advanced disease settings. Finally, we nominated alternative treatment strategies for chemorefractory PDOs using targeted agent therapeutic profiling. We propose that combined molecular and therapeutic profiling of PDOs may predict clinical response and enable prospective therapeutic selection. New approaches to prioritize treatment strategies are urgently needed to improve survival and quality of life for patients with pancreatic cancer. Combined genomic, transcriptomic, and therapeutic profiling of PDOs can identify molecular and functional subtypes of pancreatic cancer, predict therapeutic responses, and facilitate precision medicine for patients with pancreatic cancer. .

A model of the Io plasma torus has been constructed using the in situ plasma measurements of Voyager 1. A sharp gradient in plasma temperature of ∼7 × 105 K RJ−1 at 5.7 RJ divides the torus into two parts, a cold inner region, where the ions are closely confined to the centrifugal equator, and a warm outer region, which includes the orbit of Io and has a thickness scale height of 1 RJ. The outer edge of the warm torus is defined by a drop in plasma density near 7.5 RJ. The bulk motion of the plasma, i.e., the average velocity vector, is within 1% of the value expected on the basis of strict corotation in the inner part of the torus but probably deviates by 5 to 10% from corotation outside the torus. This breakdown from corotation may occur at the outer boundary of the warm torus. The energy per charge spectra show well‐resolved peaks in the inner part of the torus but strongly overlapping peaks in the outer part. In the inner torus there is a significant variation in the abundances of different ionic species over spatial scales <104 km. However, in the plasma sheet of the middle magnetosphere the ionic composition appears to be uniform from 12 to 42 RJ and is strongly dominated by ions with a ratio of atomic mass to charge of 16. These ions are most probably some combination of O+ and S2+ ions. One consequence of the observation is that the Alfven speed is uniformly low in the outer part of the torus, with values less than 250 km s−1.

We investigate the association of high-speed solar wind with coronal holes during the Skylab mission by: (1) direct comparison of solar wind and coronal X-ray data; (2) comparison of nearequatorial coronal hole area with maximum solar wind velocity in the associated streams; and (3) examination of the correlation between solar and interplanetary magnetic polarities. We find that all large near-equatorial coronal holes seen during the Skylab period were associated with high-velocity solar wind streams observed at 1 AU.

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