Multi-scale resource selection modeling is used to identify factors that limit species distributions across scales of space and time. This multi-scale nature of habitat suitability complicates the translation of inferences to single, spatial depictions of habitat required for conservation of species. We estimated resource selection functions (RSFs) across three scales for a threatened ungulate, woodland caribou (Rangifer tarandus caribou), with two objectives: (1) to infer the relative effects of two forms of anthropogenic disturbance (forestry and linear features) on woodland caribou distributions at multiple scales and (2) to estimate scale-integrated resource selection functions (SRSFs) that synthesize results across scales for management-oriented habitat suitability mapping. We found a previously undocumented scale-specific switch in woodland caribou response to two forms of anthropogenic disturbance. Caribou avoided forestry cut-blocks at broad scales according to first- and second-order RSFs and avoided linear features at fine scales according to third-order RSFs, corroborating predictions developed according to predator-mediated effects of each disturbance type. Additionally, a single SRSF validated as well as each of three single-scale RSFs when estimating habitat suitability across three different spatial scales of prediction. We demonstrate that a single SRSF can be applied to predict relative habitat suitability at both local and landscape scales in support of critical habitat identification and species recovery.

Summary1. Caribou and reindeer Rangifer tarandus are declining across North America and Scandinavia in part from wolf Canis lupus-mediated apparent competition with more abundant ungulate prey species. While caribou generally persist in areas with low wolf density, wolf packs that overlap caribou ranges could trigger caribou declines. Moreover, anthropogenic linear features such as roads, trails and seismic lines are hypothesized to increase predation risk for caribou, yet few studies have examined the mechanistic effects of linear features or spatial overlap on wolf-caribou encounter rates and predation risk. 2. We used (a) time-to-event models of wolf-caribou encounters estimated from concurrent global positioning system (GPS) radio-collar data from wolves and caribou and (b) wolf resource selection models of travel locations, to determine the potential influence of wolf-caribou spatial overlap, linear features, elevation and season on encounter rates. Analyses were based on data from 35 adult female caribou and 37 male and female wolves from 11 wolf packs from Banff and Jasper National Parks, Canada, from 2002 until 2010. 3. Wolf-caribou encounter rates increased with high wolf-caribou overlap, proximity to linear features and lower elevations. Wolves strongly selected low elevations, especially during winter and spring. Selection for linear features as travel routes increased with elevation. 4. Caribou risk of encounter was highest during the summer and autumn when wolves spent the most time at high elevations. Most wolf-caused mortalities (n = 12) occurred during spring and summer. 5. Synthesis and applications. The presence of anthropogenic linear features and the amount of time wolves spend in caribou range could be equally as important as wolf density when prioritizing caribou recovery actions such as wolf or primary prey reductions or re-introductions. The use of GPS locations and time-to-event modelling offers a powerful tool for evaluating factors affecting predation risk of threatened and endangered species.

Small cell lung cancer (SCLC) is a highly aggressive malignancy with poor survival rates, with initial responses nearly invariably followed by rapid recurrence of therapy-resistant disease. Drug resistance in SCLC may be attributable to the persistence of a subpopulation of cancer stem-like cells (CSC) that exhibit multiple drug resistance. In this study, we characterized the expression of CD133, one important marker of CSC in other cancers, in SCLC cancer cells. CD133 expression correlated with chemoresistance and increased tumorigenicity in vitro and in vivo accompanied by increased expression of Akt/PKB and Bcl-2. CD133 expression was increased in mouse and human SCLC after chemotherapy, an observation confirmed in clinical specimens isolated longitudinally from a patient receiving chemotherapy. We discovered in CD133 þ SCLC cells, an increased expression of the mitogenic neuropeptide receptors for gastrin-releasing peptide and arginine vasopressin. Notably, these cells exhibited increased sensitivity to the growth inhibitory and proapoptotic effects of a novel broad spectrum neuropeptide antagonist (related to SP-G), which has completed a phase I clinical trial for SCLC. Our results offer evidence that this agent can preferentially target chemoresistant CD133 þ cells with CSC character in SCLC, emphasizing its potential utility for improving therapy in this setting. Cancer Res; 74(5); 1554-65. Ó2014 AACR.