71 research outputs found

    Engineering Genetic Predisposition in Human Neuroepithelial Stem Cells Recapitulates Medulloblastoma Tumorigenesis.

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    Human neural stem cell cultures provide progenitor cells that are potential cells of origin for brain cancers. However, the extent to which genetic predisposition to tumor formation can be faithfully captured in stem cell lines is uncertain. Here, we evaluated neuroepithelial stem (NES) cells, representative of cerebellar progenitors. We transduced NES cells with MYCN, observing medulloblastoma upon orthotopic implantation in mice. Significantly, transcriptomes and patterns of DNA methylation from xenograft tumors were globally more representative of human medulloblastoma compared to a MYCN-driven genetically engineered mouse model. Orthotopic transplantation of NES cells generated from Gorlin syndrome patients, who are predisposed to medulloblastoma due to germline-mutated PTCH1, also generated medulloblastoma. We engineered candidate cooperating mutations in Gorlin NES cells, with mutation of DDX3X or loss of GSE1 both accelerating tumorigenesis. These findings demonstrate that human NES cells provide a potent experimental resource for dissecting genetic causation in medulloblastoma

    Myc proteins in brain tumor development and maintenance

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    Myc proteins are often deregulated in human brain tumors, especially in embryonal tumors that affect children. Many observations have shown how alterations of these pleiotropic Myc transcription factors provide initiation, maintenance, or progression of tumors. This review will focus on the role of Myc family members (particularly c-myc and Mycn) in tumors like medulloblastoma and glioma and will further discuss how to target stabilization of these proteins for future brain tumor therapies

    Gasflödesobservatör för dieselmotorer med EGR

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    Due to stricter emission legislation, there is a need for more efficient control of diesel engines with exhaust gas recirculation(EGR). In particular, it is important to estimate the air/fuel ratio accurately in transients. Therefore a new engine gas flow model has been developed. This model divides the gas into one part for oxygen and one part for inert gases. Based on this model an observer has been designed to estimate the oxygen concentration in the gas going into the engine, which can be used to calculate the air/fuel ratio. This observer can also be used to estimate the intake manifold pressure. The advantage of estimating the pressure, instead of low pass filtering the noisy signal, is that the observer does not cause time delay
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