469 research outputs found

    Exploring Large-scale Parameterization of Irrigation in the Northern High Plains

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    Research Question – Objective - Hypothesis How does irrigation respond to the demands of Crop Irrigation Requirements under extreme hydrometeorological events? Implement a parameterization of irrigation into the land surface hydrology model VIC. Changes in evapotranspiration (ET) will be more conspicuous during dry years, highlighting the limiting role of soil moisture in the model

    Exploring Large-scale Parameterization of Irrigation in the Northern High Plains

    Get PDF
    Research Question – Objective - Hypothesis How does irrigation respond to the demands of Crop Irrigation Requirements under extreme hydrometeorological events? Implement a parameterization of irrigation into the land surface hydrology model VIC. Changes in evapotranspiration (ET) will be more conspicuous during dry years, highlighting the limiting role of soil moisture in the model

    Osteoblasts contribute to a protective niche that supports melanoma cell proliferation and survival

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    Melanoma is the deadliest form of skin cancer; a primary driver of this high level of morbidity is the propensity of melanoma cells to metastasize. When malignant tumours develop distant metastatic lesions the new local tissue niche is known to impact on the biology of the cancer cells. However, little is known about how different metastatic tissue sites impact on frontline targeted therapies. Intriguingly, melanoma bone lesions have significantly lower response to BRAF or MEK inhibitor therapies. Here, we have investigated how the cellular niche of the bone can support melanoma cells by stimulating growth and survival via paracrine signalling between osteoblasts and cancer cells. Melanoma cells can enhance the differentiation of osteoblasts leading to increased production of secreted ligands, including RANKL. Differentiated osteoblasts in turn can support melanoma cell proliferation and survival via the secretion of RANKL that elevates the levels of the transcription factor MITF, even in the presence of BRAF inhibitor. By blocking RANKL signalling, either via neutralizing antibodies, genetic alterations or the RANKL receptor inhibitor SPD304, the survival advantage provided by osteoblasts could be overcome

    Relationship of PIK3CA mutation and pathway activity with antiproliferative response to aromatase inhibition

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    INTRODUCTION: PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit α) somatic mutations are the most common genetic alteration in breast cancer (BC). Their prognostic value and that of the phosphatidylinositol 3-kinase (PI3K) pathway in BC remains only partly defined. The effect of PIK3CA mutations and alterations of the PI3K pathway on the antiproliferative response to aromatase inhibitor treatment was determined. METHODS: The Sequenom MassARRAY System was used to determine the presence of 20 somatic mutations across the PIK3CA gene in 85 oestrogen receptor–positive (ER+) BC patients treated with 2 weeks of anastrozole before surgery. Whole-genome expression profiles were used to interrogate gene signatures (GSs) associated with the PI3K pathway. Antiproliferative activity was assessed by the change in Ki67 staining between baseline and surgery. Three GSs representing the PI3K pathway were assessed (PIK3CA-GS (Loi), PI3K-GS (Creighton) and PTEN-loss-GS (Saal)). RESULTS: In our study sample, 29% of tumours presented with either a hotspot (HS, 71%) or a nonhotspot (non-HS, 29%) PIK3CA mutation. Mutations were associated with markers of good prognosis such as progesterone receptor positivity (PgR+) (P = 0.006), low grade (P = 0.028) and luminal A subtype (P = 0.039), with a trend towards significance with degree of ER positivity (P = 0.051) and low levels of Ki67 (P = 0.051). Non-HS mutations were associated with higher PgR (P = 0.014) and ER (P < 0.001) expression than both wild-type (WT) and HS-mutated samples, whereas neither biomarker differed significantly between WT and HS mutations or between HS and non-HS mutations. An inverse correlation was found between the Loi signature and both the Creighton and Saal signatures, and a positive correlation was found between the latter signatures. Lower pretreatment Ki67 levels were observed in mutation compared with WT samples (P = 0.051), which was confirmed in an independent data set. Mutation status did not predict change in Ki67 in response to 2 weeks of anastrozole treatment; there was no significant difference between HS and non-HS mutations in this regard. CONCLUSIONS: PIK3CA mutations are associated with classical markers of good prognosis and signatures of PI3K pathway activity. The presence of a PIK3CA mutation does not preclude a response to neoadjuvant anastrozole treatment

    Second SNPP Cal/Val Campaign: Environmental Data Retrieval Analysis

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    Satellite ultraspectral infrared sensors provide key data records essential for weather forecasting and climate change science. The Suomi National Polar-orbiting Partnership (Soumi NPP) satellite Environmental Data Records (EDRs) are retrieved from calibrated ultraspectral radiance or Sensor Data Records (SDRs). Understanding the accuracy of retrieved EDRs is critical. The second Suomi NPP Calibration/Validation field campaign was conducted during March 2015 with flights over Greenland. The NASA high-altitude ER-2 aircraft carrying ultraspectral interferometer sounders such as the National Airborne Sounder Testbed-Interferometer (NAST-I) flew under the Suomi NPP satellite that carries the Crosstrack Infrared Sounder (CrIS) and the Advanced Technology Microwave Sounder (ATMS). Herein we inter-compare the EDRs produced from different retrieval algorithms employed on these satellite and aircraft campaign data. The available radiosonde measurements together with the European Centre for Medium-Range Weather Forecasts (ECMWF) analyses are used to assess atmospheric temperature and moisture retrievals from the aircraft and satellite platforms. Preliminary results of this experiment under a winter, Arctic environment are presented

    First SNPP Cal/Val Campaign: Satellite and Aircraft Sounding Retrieval Intercomparison

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    Satellite ultraspectral infrared sensors provide key data records essential for weather forecasting and climate change science. The Suomi National Polar-orbiting Partnership (SNPP) satellite Environmental Data Record (EDR) is retrieved from calibrated ultraspectral radiance so called Sensor Data Record (SDR). It is critical to understand the accuracy of retrieved EDRs, which mainly depends on SDR accuracy (e.g., instrument random noise and absolute accuracy), an ill-posed retrieval system, and radiative transfer model errors. There are few approaches to validate EDR products, e.g., some common methods are to rely on radiosonde measurements, ground-based measurements, and dedicated aircraft campaign providing in-situ measurements of atmosphere and/or employing similar ultraspectral interferometer sounders. Ultraspectral interferometer sounder aboard aircraft measures SDR to retrieve EDR, which is often used to validate satellite measurements of SDR and EDR. The SNPP Calibration/Validation Campaign was conducted during May 2013. The NASA high-altitude aircraft ER-2 that carried ultraspectral interferometer sounders such as the NASA Atmospheric Sounder Testbed-Interferometer (NAST-I) flew under the SNPP satellite that carries the Cross-track Infrared Sounder (CrIS). Here we inter-compare the EDRs produced with different retrieval algorithms from SDRs measured by the sensors from satellite and aircraft. The available dropsonde and radiosonde measurements together with the European Centre for Medium-Range Weather Forecasts (ECMWF) analysis were also used to draw the conclusion from this experiment
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