Detection rate of actionable mutations in diverse cancers using a biopsy-free (blood) circulating tumor cell DNA assay.

Analysis of cell-free DNA using next-generation sequencing (NGS) is a powerful tool for the detection/monitoring of alterations present in circulating tumor DNA (ctDNA). Plasma extracted from 171 patients with a variety of cancers was analyzed for ctDNA (54 genes and copy number variants (CNVs) in three genes (EGFR, ERBB2 and MET)). The most represented cancers were lung (23%), breast (23%), and glioblastoma (19%). Ninety-nine patients (58%) had at least one detectable alteration. The most frequent alterations were TP53 (29.8%), followed by EGFR (17.5%), MET (10.5%), PIK3CA (7%), and NOTCH1 (5.8%). In contrast, of 222 healthy volunteers, only one had an aberration (TP53). Ninety patients with non-brain tumors had a discernible aberration (65% of 138 patients; in 70% of non-brain tumor patients with an alteration, the anomaly was potentially actionable). Interestingly, nine of 33 patients (27%) with glioblastoma had an alteration (6/33 (18%) potentially actionable). Overall, sixty-nine patients had potentially actionable alterations (40% of total; 69.7% of patients (69/99) with alterations); 68 patients (40% of total; 69% of patients with alterations), by a Food and Drug Administration (FDA) approved drug. In summary, 65% of diverse cancers (as well as 27% of glioblastomas) had detectable ctDNA aberration(s), with the majority theoretically actionable by an approved agent

The Proteus Navier-Stokes code

An effort is currently underway at NASA Lewis to develop two- and three-dimensional Navier-Stokes codes, called Proteus, for aerospace propulsion applications. The emphasis in the development of Proteus is not algorithm development or research on numerical methods, but rather the development of the code itself. The objective is to develop codes that are user-oriented, easily-modified, and well-documented. Well-proven, state-of-the-art solution algorithms are being used. Code readability, documentation (both internal and external), and validation are being emphasized. This paper is a status report on the Proteus development effort. The analysis and solution procedure are described briefly, and the various features in the code are summarized. The results from some of the validation cases that have been run are presented for both the two- and three-dimensional codes

Evaluating the role of sediment‐bacteria interactions on Escherichia coli concentrations at beaches in southern Lake Michigan

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102640/1/jgrc20481.pd

Modules for Experiments in Stellar Astrophysics (MESA): Convective Boundaries, Element Diffusion, and Massive Star Explosions

We update the capabilities of the software instrument Modules for Experiments in Stellar Astrophysics (MESA) and enhance its ease of use and availability. Our new approach to locating convective boundaries is consistent with the physics of convection, and yields reliable values of the convective core mass during both hydrogen and helium burning phases. Stars with $M<8\,{\rm M_\odot}$ become white dwarfs and cool to the point where the electrons are degenerate and the ions are strongly coupled, a realm now available to study with MESA due to improved treatments of element diffusion, latent heat release, and blending of equations of state. Studies of the final fates of massive stars are extended in MESA by our addition of an approximate Riemann solver that captures shocks and conserves energy to high accuracy during dynamic epochs. We also introduce a 1D capability for modeling the effects of Rayleigh-Taylor instabilities that, in combination with the coupling to a public version of the STELLA radiation transfer instrument, creates new avenues for exploring Type II supernovae properties. These capabilities are exhibited with exploratory models of pair-instability supernova, pulsational pair-instability supernova, and the formation of stellar mass black holes. The applicability of MESA is now widened by the capability of importing multi-dimensional hydrodynamic models into MESA. We close by introducing software modules for handling floating point exceptions and stellar model optimization, and four new software tools -- MESAWeb, MESA-Docker, pyMESA, and mesastar.org -- to enhance MESA's education and research impact.Comment: 64 pages, 61 figures; Accepted to AAS Journal

Detection of low prevalence somatic mutations in solid tumors with ultra-deep targeted sequencing

Ultra-deep targeted sequencing (UDT-Seq) can identify subclonal somatic mutations in tumor samples. Early assays' limited breadth and depth restrict their clinical utility. Here, we target 71 kb of mutational hotspots in 42 cancer genes. We present novel methods enhancing both laboratory workflow and mutation detection. We evaluate UDT-Seq true sensitivity and specificity (> 94% and > 99%, respectively) for low prevalence mutations in a mixing experiment and demonstrate its utility using six tumor samples. With an improved performance when run on the Illumina Miseq, the UDT-Seq assay is well suited for clinical applications to guide therapy and study clonal selection in heterogeneous samples

Instantons and the fixed point topological charge in the two-dimensional O(3) sigma-model

We define a fixed point topological charge for the two-dimensional O(3) lattice sigma-model which is free of topological defects. We use this operator in combination with the fixed point action to measure the topological susceptibility for a wide range of correlation lengths. The results strongly suggest that it is not a physical quantity in this model. The procedure, however, can be applied to other asymptotically free theories as well.Comment: 20 pages (3 figures), uuencoded compressed latex fil