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Tumor responses to cancer therapeutics are generally monitored every 2-3 months based on changes in tumor size. Dynamic biomarkers that reflect effective engagement of targeted therapeutics to the targeted pathway, so-called "effect sensors", would fulfill a need for non-invasive, drug-specific indicators of early treatment effect. Using a proteomics approach to identify effect sensors, we demonstrated MUC1 upregulation in response to epidermal growth factor receptor (EGFR)targeting treatments in breast and lung cancer models. To achieve this, using semi-quantitative mass spectrometry, we found MUC1 to be significantly and durably upregulated in response to erlotinib, an EGFR-targeting treatment. MUC1 upregulation was regulated transcriptionally, involving PI3K-signaling and STAT3. We validated these results in erlotinib-sensitive human breast and non-small lung cancer cell lines. Importantly, erlotinib treatment of mice bearing SUM149 xenografts resulted in increased MUC1 shedding into plasma. Analysis of MUC1 using serial blood sampling may therefore be a new, relatively non-invasive tool to monitor early and drug-specific effects of EGFR-targeting therapeutics.

Native American (American Indian)/Alaska Natives (AI/AN) are significantly underrepresented in the U.S. federal science and engineering (S&E) labor force. This underrepresentation extends into the leadership ranks of federal agencies responsible for designing, implementing, and maintaining resource monitoring and enforcement programs on tribal lands. Datasets documenting demographics and salaries of the federal S&E workforce show AI/AN are the smallest S&E workforce segment among minorities and receive the lowest average salaries for engineers and physical scientists. Academic statistics show AI/AN students earn significantly fewer engineering and Earth, atmospheric, and ocean science (EA&OS) bachelor's degrees than other ethnic groups and rarely earn advanced degrees in these disciplines. Additional aspects in federal and academic datasets offer clues on a spectrum of causative factors affecting the AI/AN recruitment pool for federal S&E jobs and the rarity of AI/AN ascending to leadership positions with...

Due to the devastating effects of recent hurricanes in the Gulf of Mexico (e.g., Katrina, Rita, Ike and Gustav), the development of a high-resolution, real-time, total water level prototype system has been accelerated. The fully coupled model system that includes hydrology is an extension of the ADCIRC Surge Guidance System (ASGS), and will henceforth be referred to as ASGS-STORM (Scalable, Terrestrial, Ocean, River, Meteorological) to emphasize the major processes that are represented by the system.The ASGS-STORM system incorporates tides, waves, winds, rivers and surge to produce a total water level, which provides a holistic representation of coastal flooding. ASGS-STORM was rigorously tested during Hurricane Irene, which made landfall in late August 2011 in North Carolina. All results from ASGS-STORM for the advisories were produced in real-time, forced by forecast wind and pressure fields computed using a parametric tropical cyclone model, and made available via the web. Herein, a skill assessment, analyzing wind speed and direction, significant wave heights, and total water levels, is used to evaluate ASGS-STORM's performance during Irene for three advisories and the best track from the National Hurricane Center (NHC). ASGS-STORM showed slight over-prediction for two advisories (Advisory 23 and 25) due to the over-estimation of the storm intensity. However, ASGS-STORM shows notable skill in capturing total water levels, wind speed and direction, and significant wave heights in North Carolina when utilizing Advisory 28, which had a slight shift in the track but provided a more accurate estimation of the storm intensity, along with the best track from the NHC. Results from ASGS-STORM have shown that as the forecast of the advisories improves, so does the accuracy of the models used in the study; therefore, accurate input from the weather forecast is a necessary, but not sufficient, condition to ensure the accuracy of the guidance provided by the system. While Irene provided a real-time test of the viability of a total water level system, the relatively insignificant freshwater discharges precludes definitive conclusions about the role of freshwater discharges on total water levels in estuarine zones. Now that the system has been developed, on-going work will examine storms (e.g., Floyd) for which the freshwater discharge played a more meaningful role.

This study investigates evolving methodologies for radar and merged gauge–radar quantitative precipitation estimation (QPE) to determine their influence on the flow predictions of a distributed hydrologic model. These methods include the National Mosaic and QPE algorithm package (NMQ), under development at the National Severe Storms Laboratory (NSSL), and the Multisensor Precipitation Estimator (MPE) and High-Resolution Precipitation Estimator (HPE) suites currently operational at National Weather Service (NWS) field offices. The goal of the study is to determine which combination of algorithm features offers the greatest benefit toward operational hydrologic forecasting. These features include automated radar quality control, automated Z–R selection, brightband identification, bias correction, multiple radar data compositing, and gauge–radar merging, which all differ between NMQ and MPE–HPE. To examine the spatial and temporal characteristics of the precipitation fields produced by each of the QPE methodologies, high-resolution (4 km and hourly) gridded precipitation estimates were derived by each algorithm suite for three major precipitation events between 2003 and 2006 over subcatchments within the Tar–Pamlico River basin of North Carolina. The results indicate that the NMQ radar-only algorithm suite consistently yielded closer agreement with reference rain gauge reports than the corresponding HPE radar-only estimates did. Similarly, the NMQ radar-only QPE input generally yielded hydrologic simulations that were closer to observations at multiple stream gauging points. These findings indicate that the combination of Z–R selection and freezing-level identification algorithms within NMQ, but not incorporated within MPE and HPE, would have an appreciable positive impact on hydrologic simulations. There were relatively small differences between NMQ and HPE gauge–radar estimates in terms of accuracy and impacts on hydrologic simulations, most likely due to the large influence of the input rain gauge information.

This study quantifies the spatial distribution of precipitation patterns on an annual basis for southeast Louisiana. To compile a long-term record of 24-h rainfall, rainfall reports collected by National Weather Service (NWS) cooperative observers were gathered from National Climatic Data Center (NCDC) archives, private collections of observational data held at regional and local libraries, NWS offices, and local utility providers. The reports were placed into a digital database in which each station’s record was subjected to an extensive quality control process. This process produced a database of daily rainfall reports for 59 south Louisiana stations for the period 1836–2002, with extensive documentation for each site outlining the differences between the study’s data and the data available from the NCDC Web page. A statistical methodology was developed to determine if the four NCDC climate divisions for southeast Louisiana accurately depict average monthly rainfall for the area. This method employs cluster analysis, using Euclidean distance as the measure of dissimilarity for the clustering technique. To resolve missing rainfall observations, an imputation scheme was developed that uses the two most similar stations (based on Euclidean distance) to determine appropriate values for missing rainfall observations. Results from this testing structure show statistical evidence of precipitation microclimates across south Louisiana at higher spatial scales than those of the NCDC climate zones. Quantifying the spatial extent of daily precipitation and documenting historical trends of precipitation provides critical design information for regional infrastructure within this highly vulnerable area of the central Gulf Coast region.

The objective of the Coastal and Inland Flooding Observation and Warning (CI-FLOW) project is to prototype new hydrometeorologic techniques to address a critical NOAA service gap: routine total water level predictions for tidally influenced watersheds. Since February 2000, the project has focused on developing a coupled modeling system to accurately account for water at all locations in a coastal watershed by exchanging data between atmospheric, hydrologic, and hydrodynamic models. These simulations account for the quantity of water associated with waves, tides, storm surge, rivers, and rainfall, including interactions at the tidal/surge interface. Within this project, CI-FLOW addresses the following goals: i) apply advanced weather and oceanographic monitoring and prediction techniques to the coastal environment; ii) prototype an automated hydrometeorologic data collection and prediction system; iii) facilitate interdisciplinary and multiorganizational collaborations; and iv) enhance techniques and techn...

The National Mosaic and Multi-sensor QPE (Quantitative Precipitation Estimation), or “NMQ”, system was initially developed from a joint initiative between the National Oceanic and Atmospheric Administration's National Severe Storms Laboratory, the Federal Aviation Administration's Aviation Weather Research Program, and the Salt River Project. Further development has continued with additional support from the National Weather Service (NWS) Office of Hydrologic Development, the NWS Office of Climate, Water, and Weather Services, and the Central Weather Bureau of Taiwan. The objectives of NMQ research and development (R&D) are 1) to develop a hydrometeorological platform for assimilating different observational networks toward creating high spatial and temporal resolution multisensor QPEs for f lood warnings and water resource management and 2) to develop a seamless high-resolution national 3D grid of radar reflectivity for severe weather detection, data assimilation, numerical weather prediction model verification, and aviation product development. Through about ten years of R&D, a real-time NMQ system has been implemented (http://nmq.ou.edu). Since June 2006, the system has been generating high-resolution 3D reflectivity mosaic grids (31 vertical levels) and a suite of severe weather and QPE products in real-time for the conterminous United States at a 1-km horizontal resolution and 2.5 minute update cycle. The experimental products are provided in real-time to end users ranging from government agencies, universities, research institutes, and the private sector and have been utilized in various meteorological, aviation, and hydrological applications. Further, a number of operational QPE products generated from different sensors (radar, gauge, satellite) and by human experts are ingested in the NMQ system and the experimental products are evaluated against the operational products as well as independent gauge observations in real time. The NMQ is a fully automated system. It facilitates systematic evaluations and advances of hydrometeorological sciences and technologies in a real-time environment and serves as a test bed for rapid science-to-operation infusions. This paper describes scientific components of the NMQ system and presents initial evaluation results and future development plans of the system.