158 research outputs found
Methods for Extremely Sparse-Angle Proton Tomography
Proton radiography is a widely-fielded diagnostic used to measure magnetic
structures in plasma. The deflection of protons with multi-MeV kinetic energy
by the magnetic fields is used to infer their path-integrated field strength.
Here, the use of tomographic methods is proposed for the first time to lift the
degeneracy inherent in these path-integrated measurements, allowing full
reconstruction of spatially resolved magnetic field structures in three
dimensions. Two techniques are proposed which improve the performance of
tomographic reconstruction algorithms in cases with severely limited numbers of
available probe beams, as is the case in laser-plasma interaction experiments
where the probes are created by short, high-power laser pulse irradiation of
secondary foil targets. The methods are equally applicable to optical probes
such as shadowgraphy and interferometry [M. Kasim et al. Phys. Rev. E 95,
023306 (2017)], thereby providing a disruptive new approach to three
dimensional imaging across the physical sciences and engineering disciplines.Comment: 11 pages, 6 figures, companion article to arXiv:2103.1126
Recommended from our members
Discovery of a Potent and Selective DDR1 Receptor Tyrosine Kinase Inhibitor
The DDR1 receptor tyrosine kinase is activated by matrix collagens and has been implicated in numerous cellular functions such as proliferation, differentiation, adhesion, migration, and invasion. Here we report the discovery of a potent and selective DDR1 inhibitor, DDR1-IN-1, and present the 2.2 Å DDR1 co-crystal structure. DDR1-IN-1 binds to DDR1 in the ‘DFG-out’ conformation and inhibits DDR1 autophosphorylation in cells at submicromolar concentrations with good selectivity as assessed against a panel of 451 kinases measured using the KinomeScan technology. We identified a mutation in the hinge region of DDR1, G707A, that confers >20-fold resistance to the ability of DDR1-IN-1 to inhibit DDR1 autophosphorylation and can be used to establish what pharmacology is DDR1-dependent. A combinatorial screen of DDR1-IN-1 with a library of annotated kinase inhibitors revealed that inhibitors of PI3K and mTOR such as GSK2126458 potentiate the antiproliferative activity of DDR1-IN-1 in colorectal cancer cell lines. DDR1-IN-1 provides a useful pharmacological probe for DDR1-dependent signal transduction
Structure and evolutionary origin of Ca2+-dependent herring type II antifreeze protein
10.1371/journal.pone.0000548PLoS ONE26
Network-Based Pipeline for Analyzing MS Data: An Application toward Liver Cancer
10.1021/pr1010845Journal of Proteome Research1052261-2272JPRO
The Intracellular Transport and Secretion of Calumenin-1/2 in Living Cells
Calumenin isoforms 1 and 2 (calu-1/2), encoded by the CALU gene, belong to the CREC protein family. Calu-1/2 proteins are secreted into the extracellular space, but the secretory process and regulatory mechanism are largely unknown. Here, using a time-lapse imaging system, we visualized the intracellular transport and secretory process of calu-1/2-EGFP after their translocation into the ER lumen. Interestingly, we observed that an abundance of calu-1/2-EGFP accumulated in cellular processes before being released into the extracellular space, while only part of calu-1/2-EGFP proteins were secreted directly after attaching to the cell periphery. Moreover, we found the secretion of calu-1/2-EGFP required microtubule integrity, and that calu-1/2-EGFP-containing vesicles were transported by the motor proteins Kif5b and cytoplasmic dynein. Finally, we determined the export signal of calu-1/2-EGFP (amino acid positions 20–46) and provided evidence that the asparagine at site 131 was indispensable for calu-1/2-EGFP stabilization. Taken together, we provide a detailed picture of the intracellular transport of calu-1/2-EGFP, which facilitates our understanding of the secretory mechanism of calu-1/2
Comprehensive and Integrated Genomic Characterization of Adult Soft Tissue Sarcomas
Sarcomas are a broad family of mesenchymal malignancies exhibiting remarkable histologic diversity. We describe the multi-platform molecular landscape of 206 adult soft tissue sarcomas representing 6 major types. Along with novel insights into the biology of individual sarcoma types, we report three overarching findings: (1) unlike most epithelial malignancies, these sarcomas (excepting synovial sarcoma) are characterized predominantly by copy-number changes, with low mutational loads and only a few genes (, , ) highly recurrently mutated across sarcoma types; (2) within sarcoma types, genomic and regulomic diversity of driver pathways defines molecular subtypes associated with patient outcome; and (3) the immune microenvironment, inferred from DNA methylation and mRNA profiles, associates with outcome and may inform clinical trials of immune checkpoint inhibitors. Overall, this large-scale analysis reveals previously unappreciated sarcoma-type-specific changes in copy number, methylation, RNA, and protein, providing insights into refining sarcoma therapy and relationships to other cancer types
- …