Deconvolution from Wavefront Sensing Using Optimal Wavefront Estimators

A cost effective method to improve the space surveillance mission performance of United States Air Force (USAF) ground-based telescopes is investigated and improved. A minimum variance wavefront estimation technique is used to improve Deconvolution from Wavefront Sensing (DWFS), a method to mitigate the effects of atmospheric turbulence on imaging systems that does not require expensive adaptive optics. Both least-squares and minimum variance wavefront phase estimation techniques are investigated, using both Gaussian and Zernike polynomial elementary functions. Imaging simulations and established performance metrics are used to evaluate these wavefront estimation techniques for a one-meter optical telescope. Performance metrics include the average pupil-averaged mean square phase error of the residual wavefront, the average system transfer function, the signal-to-noise ratio (SNR) of the system transfer function, and the optical transfer function correlation. Results show that the minimum variance estimation technique that employs Zernike polynomial elementary functions offers improvements over all other estimation techniques in each of the performance metrics. Extended object simulations are also conducted which demonstrate the improvements in image quality and resolution that result from the modifications to the DWFS method. Implementation of the DWFS method into USAF space surveillance telescopes is investigated

Misguided Transcriptional Elongation Causes Mixed Lineage Leukemia

Investigation of the activity of a family of fusion proteins that cause aggressive leukemia suggests transcriptional elongation as a new mechanism for oncogenic transformation

MLL-fusion-driven leukemia requires SETD2 to safeguard genomic integrity

MLL-fusions represent a large group of leukemia drivers, whose diversity originates from the vast molecular heterogeneity of C-terminal fusion partners of MLL. While studies of selected MLL-fusions have revealed critical molecular pathways, unifying mechanisms across all MLL-fusions remain poorly understood. We present the first comprehensive survey of protein-protein interactions of seven distantly related MLL-fusion proteins. Functional investigation of 128 conserved MLL-fusion-interactors identifies a specific role for the lysine methyltransferase SETD2 in MLL-leukemia. SETD2 loss causes growth arrest and differentiation of AML cells, and leads to increased DNA damage. In addition to its role in H3K36 tri-methylation, SETD2 is required to maintain high H3K79 di-methylation and MLL-AF9-binding to critical target genes, such as Hoxa9. SETD2 loss synergizes with pharmacologic inhibition of the H3K79 methyltransferase DOT1L to induce DNA damage, growth arrest, differentiation, and apoptosis. These results uncover a dependency for SETD2 during MLL-leukemogenesis, revealing a novel actionable vulnerability in this disease

MLL-ENL Inhibits Polycomb Repressive Complex 1 to Achieve Efficient Transformation of Hematopoietic Cells

Stimulation of transcriptional elongation is a key activity of leukemogenic MLL fusion proteins. Here, we provide evidence that MLL-ENL also inhibits Polycomb-mediated silencing as a prerequisite for efficient transformation. Biochemical studies identified ENL as a scaffold that contacted the elongation machinery as well as the Polycomb repressive complex 1 (PRC1) component CBX8. These interactions were mutually exclusive in vitro, corresponding to an antagonistic behavior of MLL-ENL and CBX8 in vivo. CBX8 inhibited elongation in a specific reporter assay, and this effect was neutralized by direct association with ENL. Correspondingly, CBX8-binding-defective MLL-ENL could not fully activate gene loci necessary for transformation. Finally, we demonstrate dimerization of MLL-ENL as a neomorphic activity that may augment Polycomb inhibition and transformation

Untersuchung von Massnahmen zur Minderung der Geraeuschemission bei Ultraleichtflugzeugen

With 2 refs., 74 figs., 13 tabs.TIB: RN 8908(90-007) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman