Discovery of a Nova-Like Cataclysmic Variable in the Kepler Mission Field

We announce the identification of a new cataclysmic variable star in the field of the Kepler Mission, KIC J192410.81+445934.9. This system was identified during a search for compact pulsators in the Kepler field. High-speed photometry reveals coherent large-amplitude variability with a period of 2.94 h. Rapid, large-amplitude quasi-periodic variations are also detected on time scales of ~1200 s and ~650 s. Time-resolved spectroscopy covering one half photometric period shows shallow, broad Balmer and He I absorption lines with bright emission cores as well as strong He II and Bowen blend emission. Radial velocity variations are also observed in the Balmer and He I emission lines that are consistent with the photometric period. We therefore conclude that KIC J192410.81+445934.9 is a nova-like variable of the UX UMa class in or near the period gap, and it may belong to the rapidly growing subclass of SW Sex systems. Based on 2MASS photometry and companion star models, we place a lower limit on the distance to the system of ~500 pc. Due to limitations of our discovery data, additional observations including spectroscopy and polarimetry are needed to confirm the nature of this object. Such data will help to further understanding of the behavior of nova-like variables in the critical period range of 3-4 h, where standard cataclysmic variable evolutionary theory finds major problems. The presence of this system in the Kepler mission field-of-view also presents a unique opportunity to obtain a continuous photometric data stream of unparalleled length and precision on a cataclysmic variable system.Comment: Accepted for publication in the Astronomical Journal. 8 pages, 7 figures, uses emulateapj

Integration of decision support systems to improve decision support performance

Decision support system (DSS) is a well-established research and development area. Traditional isolated, stand-alone DSS has been recently facing new challenges. In order to improve the performance of DSS to meet the challenges, research has been actively carried out to develop integrated decision support systems (IDSS). This paper reviews the current research efforts with regard to the development of IDSS. The focus of the paper is on the integration aspect for IDSS through multiple perspectives, and the technologies that support this integration. More than 100 papers and software systems are discussed. Current research efforts and the development status of IDSS are explained, compared and classified. In addition, future trends and challenges in integration are outlined. The paper concludes that by addressing integration, better support will be provided to decision makers, with the expectation of both better decisions and improved decision making processes

Brigatinib causes tumor shrinkage in both NF2-deficient meningioma and schwannoma through inhibition of multiple tyrosine kinases but not ALK

Neurofibromatosis Type 2 (NF2) is an autosomal dominant genetic syndrome caused by mutations in the NF2 tumor suppressor gene resulting in multiple schwannomas and meningiomas. There are no FDA approved therapies for these tumors and their relentless progression results in high rates of morbidity and mortality. Through a combination of high throughput screens, preclinical in vivo modeling, and evaluation of the kinome en masse, we identified actionable drug targets and efficacious experimental therapeutics for the treatment of NF2 related schwannomas and meningiomas. These efforts identified brigatinib (ALUNBRIG®), an FDA-approved inhibitor of multiple tyrosine kinases including ALK, to be a potent inhibitor of tumor growth in established NF2 deficient xenograft meningiomas and a genetically engineered murine model of spontaneous NF2 schwannomas. Surprisingly, neither meningioma nor schwannoma cells express ALK. Instead, we demonstrate that brigatinib inhibited multiple tyrosine kinases, including EphA2, Fer and focal adhesion kinase 1 (FAK1). These data demonstrate the power of the de novo unbiased approach for drug discovery and represents a major step forward in the advancement of therapeutics for the treatment of NF2 related malignancies

Scientific foundations for an IUCN Red List of ecosystems

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Microbiota-derived 3-IAA influences chemotherapy efficacy in pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) is expected to be the second most deadly cancer by 2040, owing to the high incidence of metastatic disease and limited responses to treatment. Less than half of all patients respond to the primary treatment for PDAC, chemotherapy, and genetic alterations alone cannot explain this. Diet is an environmental factor that can influence the response to therapies, but its role in PDAC is unclear. Here, using shotgun metagenomic sequencing and metabolomic screening, we show that the microbiota-derived tryptophan metabolite indole-3-acetic acid (3-IAA) is enriched in patients who respond to treatment. Faecal microbiota transplantation, short-term dietary manipulation of tryptophan and oral 3-IAA administration increase the efficacy of chemotherapy in humanized gnotobiotic mouse models of PDAC. Using a combination of loss- and gain-of-function experiments, we show that the efficacy of 3-IAA and chemotherapy is licensed by neutrophil-derived myeloperoxidase. Myeloperoxidase oxidizes 3-IAA, which in combination with chemotherapy induces a downregulation of the reactive oxygen species (ROS)-degrading enzymes glutathione peroxidase 3 and glutathione peroxidase 7. All of this results in the accumulation of ROS and the downregulation of autophagy in cancer cells, which compromises their metabolic fitness and, ultimately, their proliferation. In humans, we observed a significant correlation between the levels of 3-IAA and the efficacy of therapy in two independent PDAC cohorts. In summary, we identify a microbiota-derived metabolite that has clinical implications in the treatment of PDAC, and provide a motivation for considering nutritional interventions during the treatment of patients with cancer.</p