Project description:In order to identify mechanisms of drug resistance to HER2-targeted therapy, we performed cDNA microarray analysis on drug naiive BT474 and drug resistant BT474 cells treated with lapatinib for 0, 10, and 20 hrs.
Project description:The oil and gas (O&G) sector represents a large source of greenhouse gas (GHG) emissions globally. However, estimates of O&G emissions rely upon bottom-up approaches, and are rarely evaluated through atmospheric measurements. Here, we use aircraft measurements over the Canadian oil sands (OS) to derive the first top-down, measurement-based determination of the their annual CO2 emissions and intensities. The results indicate that CO2 emission intensities for OS facilities are 13-123% larger than those estimated using publically available data. This leads to 64% higher annual GHG emissions from surface mining operations, and 30% higher overall OS GHG emissions (17 Mt) compared to that reported by industry, despite emissions reporting which uses the most up to date and recommended bottom-up approaches. Given the similarity in bottom-up reporting methods across the entire O&G sector, these results suggest that O&G CO2 emissions inventory data may be more uncertain than previously considered.
Project description:Measurement-based estimates of greenhouse gas (GHG) emissions from complex industrial operations are challenging to obtain, but serve as an important, independent check on inventory-reported emissions. Such top-down estimates, while important for oil and gas (O&G) emissions globally, are particularly relevant for Canadian oil sands (OS) operations, which represent the largest O&G contributor to national GHG emissions. We present a multifaceted top-down approach for estimating CO2 emissions that combines aircraft-measured CO2/NOx emission ratios (ERs) with inventory and satellite-derived NOx emissions from Ozone Monitoring Instrument (OMI) and TROPOspheric Ozone Monitoring Instrument (TROPOMI) and apply it to the Athabasca Oil Sands Region (AOSR) in Alberta, Canada. Historical CO2 emissions were reconstructed for the surface mining region, and average top-down estimates were found to be >65% higher than facility-reported, bottom-up estimates from 2005 to 2020. Higher top-down vs. bottom-up emissions estimates were also consistently obtained for individual surface mining and in situ extraction facilities, which represent a growing category of energy-intensive OS operations. Although the magnitudes of the measured discrepancies vary between facilities, they combine such that the observed reporting gap for total AOSR emissions is ≥(31 ± 8) Mt for each of the last 3 years (2018-2020). This potential underestimation is large and broadly highlights the importance of continued review and refinement of bottom-up estimation methodologies and inventories. The ER method herein offers a powerful approach for upscaling measured facility-level or regional fossil fuel CO2 emissions by taking advantage of satellite remote sensing observations.
Project description:To identify mechanisms that regulate V(D)J recombination, we used proximity-dependent biotin identification to analyze the interactomes of full length and truncated forms of RAG1 in pre-B cells. This revealed an association of RAG1 with numerous nucleolar proteins in a manner dependent on amino acids 216-383 and allowed identification of a motif required for nucleolar localization. Experiments in transformed pre-B cell lines and cultured primary pre-B cells reveal a strong correlation between disruption of nucleoli, reduced association of RAG1 with a nucleolar marker, and increases in V(D)J recombination activity. Mutation of the RAG1 nucleolar localization motif boosts recombination while removal of the first 215 amino acids of RAG1, which are required for efficient egress from nucleoli, reduces recombination activity. Our findings indicate that nucleolar sequestration of RAG1 is a negative regulatory mechanism in V(D)J recombination and identify regions of the RAG1 N-terminal region that control nucleolar association and egress.