University of Northern British Columbia. College of Science and Management

Snow plays an important role on the hydrological cycle of watersheds in cold regions. Predicting timing and magnitude of snow accumulation and ablation is necessary for water management in different sectors. A spatially distributed snow model (SnowModel) is chosen for our research, which is forced by meteorological data provided from automated weather stations. SnowModel is evaluated for two watersheds in southeast of BC. Two consecutive year (2006-2008) are selected for the calibration and validation processes. Simulated snow depth and snow water equivalent (SWE) are compared with observed data from snow pillows. Two error factors of Nash-Sutcliffe Efficiency Index, and R-squared show 0.96, 0.98 values in accumulation period and 0.87, 0.86 for ablation period, respectively. Spatially distribution of snow depth and SWE over domains also are discussed. In general, SnowModel is able to estimate the accumulated snow depth and SWE in alpine areas in a high level of accuracy.

The first part of this thesis investigated the growth-inhibitory and immunomodulatory potential of six wild Canadian mushrooms. Out of 24 crude extracts, six showed strong growth-inhibitory activity, two exhibited strong immuno-stimulatory activity and nine demonstrated potent anti-inflammatory activity. The second part of this thesis involved purification and characterization of growth-inhibitory compounds from Albatrellus flettii. Liquid-liquid extraction, Sephadex LH-20 and HPLC-Mass Spectrometry (HPLC-MS) were used to purify the three compounds of interest. NMR analyses confirmed their identity as grifolin, neogrifolin and confluentin. Grifolin and neogrifolin inhibited IMP1-KRas RNA interaction as demonstrated using an in-vitro fluorescent polarization assay. The three compounds suppressed KRas expression in SW480 and HT-29 human colon cancer cells. Confluentin, shown for the first time, to induce apoptosis and arrest cell cycle in SW480 cells. The third part of this thesis involved the development of methods to purify growth-inhibitory compounds from Sarcodon scabripes. HPLC-MS detected some potential novel compounds.

Intermontane lakes are often enclosed by complex topography that creates difficulty in resolving the local and regional wind fields. Quesnel Lake, nestled into the western flank of the Cariboo Mountains in central British Columbia, is one such lake. This study examines the wind climatology of Quesnel Lake at three distinct spatial and temporal scales. Firstly, long-term wind data from meteorological stations bordering the Cariboo Mountains exhibit a cycle of calm and active periods throughout the year. Secondly, an environmentto- circulation synoptic climatology is presented that illustrates the large-scale atmospheric patterns that lead to strong wind events at the lake. Finally, the spatial and temporal variability of the near-surface wind field has been examined using an array of shore-based meteorological stations. The response of the wind field to synoptic forcing is found to be driven primarily by the orientation of the regional 800 hPa pressure gradient. iii

This thesis study analyzed the land use and land cover (LULC) changes in Stoney Creek Watershed, BC, Canada using the combination of remote sensing, GIS and modeling approaches. The Object-Based Image Analysis (OBIA) tool in PCI Geomatica 2017 software was applied to generate unsupervised classification LULC maps using Landsat TM and OLI images of the years 1986, 1999 and 2016. Various band ratio were computed to improve different classification results. Esri ArcMap 10.5 was used to produce all the LULC maps for subsequent modeling. A modeling method using Multi-layer perceptron (MLP) neural network and Markov Chain (MC) was performed to predict LULC changes in 2026, using hard and soft prediction results. The outcomes of this study could provide valuable information of LULC patterns and dynamics for supporting both environmental and economic development in this area.

KRAS-driven cancers are notoriously difficult to treat due to poor pharmacodynamics of downstream inhibitors and resistance to anti-EGFR drugs. IMP-1 is a post-transcriptional regulator of KRAS mRNA. As a novel therapeutic approach, the targeting of the IMP-1-KRAS mRNA complex with a spiropyrrolizidine derivative (UNBC152), was studied. LC-MS analysis of UNBC152 indicated presence of impurities. The purpose of this study was to synthesize UNBC152 and determine the responsible bioactive molecule within the impurities. LC-MS and TLC suggested the presence of a bioactive [3+3] cycloaddition side product (SPOPP) in UNBC152. SPOPP suppressed KRAS expression in human colorectal cancer cells. Fluorescence polarization determined that SPOPP did not impact the IMP-1-KRAS mRNA interaction. SPOPP induced G2/M cell cycle arrest as shown by flow cytometry. MTT assay confirmed the SPOPP-induced growth inhibition in SW480 (IC50 = 4.17 μM) and HT29 (IC50 = 6.76 μM). These findings represent a first reporting on the bioactivity of SPOPP.