52 research outputs found
Free Energy Self-Averaging in Protein-Sized Random Heteropolymers
Current theories of heteropolymers are inherently macrpscopic, but are
applied to folding proteins which are only mesoscopic. In these theories, one
computes the averaged free energy over sequences, always assuming that it is
self-averaging -- a property well-established only if a system with quenched
disorder is macroscopic. By enumerating the states and energies of compact 18,
27, and 36mers on a simplified lattice model with an ensemble of random
sequences, we test the validity of the self-averaging approximation. We find
that fluctuations in the free energy between sequences are weak, and that
self-averaging is a valid approximation at the length scale of real proteins.
These results validate certain sequence design methods which can exponentially
speed up computational design and greatly simplify experimental realizations.Comment: 4 pages, 3 figure
Integrated genomic characterization of pancreatic ductal adenocarcinoma
We performed integrated genomic, transcriptomic, and proteomic profiling of 150 pancreatic ductal adenocarcinoma (PDAC) specimens, including samples with characteristic low neoplastic cellularity. Deep whole-exome sequencing revealed recurrent somatic mutations in KRAS, TP53, CDKN2A, SMAD4, RNF43, ARID1A, TGFβR2, GNAS, RREB1, and PBRM1. KRAS wild-type tumors harbored alterations in other oncogenic drivers, including GNAS, BRAF, CTNNB1, and additional RAS pathway genes. A subset of tumors harbored multiple KRAS mutations, with some showing evidence of biallelic mutations. Protein profiling identified a favorable prognosis subset with low epithelial-mesenchymal transition and high MTOR pathway scores. Associations of non-coding RNAs with tumor-specific mRNA subtypes were also identified. Our integrated multi-platform analysis reveals a complex molecular landscape of PDAC and provides a roadmap for precision medicine
The Longings and limits of global citizenship education : the moral pedagogy of schooling in a cosmopolitan age/ Dill
xiv, 186 p.: ill.; 23 cm
- …