University of Colorado Boulder

About: University of Colorado Boulder is a education organization based out in Boulder, Colorado, United States. It is known for research contribution in the topics: Population & Galaxy. The organization has 48794 authors who have published 115151 publications receiving 5387328 citations. The organization is also known as: CU Boulder & UCB.

Safety and Antitumor Activity of the Multitargeted Pan-TRK, ROS1, and ALK Inhibitor Entrectinib: Combined Results from Two Phase I Trials (ALKA-372-001 and STARTRK-1).

Abstract: Entrectinib, a potent oral inhibitor of the tyrosine kinases TRKA/B/C, ROS1, and ALK, was evaluated in two phase I studies in patients with advanced or metastatic solid tumors, including patients with active central nervous system (CNS) disease. Here, we summarize the overall safety and report the antitumor activity of entrectinib in a cohort of patients with tumors harboring NTRK1/2/3, ROS1, or ALK gene fusions, naive to prior TKI treatment targeting the specific gene, and who were treated at doses that achieved therapeutic exposures consistent with the recommended phase II dose. Entrectinib was well tolerated, with predominantly Grades 1/2 adverse events that were reversible with dose modification. Responses were observed in non-small cell lung cancer, colorectal cancer, mammary analogue secretory carcinoma, melanoma, and renal cell carcinoma, as early as 4 weeks after starting treatment and lasting as long as >2 years. Notably, a complete CNS response was achieved in a patient with SQSTM1-NTRK1-rearranged lung cancer.Significance: Gene fusions of NTRK1/2/3, ROS1, and ALK (encoding TRKA/B/C, ROS1, and ALK, respectively) lead to constitutive activation of oncogenic pathways. Entrectinib was shown to be well tolerated and active against those gene fusions in solid tumors, including in patients with primary or secondary CNS disease. Cancer Discov; 7(4); 400-9. ©2017 AACR.This article is highlighted in the In This Issue feature, p. 339.

Arctic Sea Ice Variability in the Context of Recent Atmospheric Circulation Trends

Abstract: Forty years (1958–97) of reanalysis products and corresponding sea ice concentration data are used to document Arctic sea ice variability and its association with surface air temperature (SAT) and sea level pressure (SLP) throughout the Northern Hemisphere extratropics. The dominant mode of winter (January–March) sea ice variability exhibits out-of-phase fluctuations between the western and eastern North Atlantic, together with a weaker dipole in the North Pacific. The time series of this mode has a high winter-to-winter autocorrelation (0.69) and is dominated by decadal-scale variations and a longer-term trend of diminishing ice cover east of Greenland and increasing ice cover west of Greenland. Associated with the dominant pattern of winter sea ice variability are large-scale changes in SAT and SLP that closely resemble the North Atlantic oscillation. The associated SAT and surface sensible and latent heat flux anomalies are largest over the portions of the marginal sea ice zone in which the tr...

Seasonal dynamics of previously unknown fungal lineages in tundra soils.

Abstract: The finding that microbial communities are active under snow has changed the estimated global rates of biogeochemical processes beneath seasonal snow packs. We used microbiological and molecular techniques to elucidate the phylogenetic composition of undersnow microbial communities in Colorado, the United States. Here, we show that tundra soil microbial biomass reaches its annual peak under snow, and that fungi account for most of the biomass. Phylogenetic analysis of tundra soil fungi revealed a high diversity of fungi and three novel clades that constitute major new groups of fungi (divergent at the subphylum or class level). An abundance of previously unknown fungi that are active beneath the snow substantially broadens our understanding of both the diversity and biogeochemical functioning of fungi in cold environments.

Back to the Beginning: Persistence and the Cross-Section of Corporate Capital Structure

Abstract: We examine the evolution of corporate capital structures and find that little of the variation in leverage is captured by previously identified determinants, such as size, market-to-book, profitability, industry, etc. Instead, the majority of variation in leverage ratios is driven by an unobserved time-invariant effect that generates surprisingly stable capital structures: High (low) levered firms tend to remain as such for over two decades. Additionally, this feature of leverage is robust to firm exit, is present prior to the IPO, and is largely unaffected by the process of going public, suggesting that variation in capital structures is primarily explained by factors that remain relatively stable for long periods of time.