Structural relaxation in the hydrogen-bonding liquids N-methylacetamide and water studied by optical Kerr-effect spectroscopy

Structural relaxation in the peptide model N-methylacetamide (NMA) is studied experimentally by ultrafast optical Kerr-effect spectroscopy over the normal-liquid temperature range and compared to the relaxation measured in water at room temperature. It is seen that in both hydrogen-bonding liquids, beta relaxation is present and in each case it is found that this can be described by the Cole-Cole function. For NMA in this temperature range, the alpha and beta relaxations are each found to have an Arrhenius temperature dependence with indistinguishable activation energies. It is known that the variations on the Debye function, including the Cole-Cole function, are unphysical, and we introduce two general modifications: one allows for the initial rise of the function, determined by the librational frequencies, and the second allows the function to be terminated in the alpha relaxation

Learn to Fly Test Setup and Concept of Operations

The NASA Learn-to-Fly (L2F) project recently completed a series of flight demonstrations of its learning algorithm for flight control at Fort A. P. Hill in Virginia. This paper discusses the test setup and concept of operations (ConOps) used by the L2F team. Unmanned airframe demonstrators for testing the research algorithms included a modified commercial off-the-shelf subscale powered airplane, plus four gliders two of which had an unconventional configuration and were fabricated using a rapid prototyping technique. Avionics system similarities and differences between the test aircraft are described, as well as ground testing in preparation for flight. The ConOps discussion includes the development of a tethered helium balloon drop launch technique for the glider demonstrators. This launch method was chosen for its potential to be inexpensive and allow for rapid turn-around for multiple glider launches but it also presented challenges, such as balloon tether avoidance, high angle of attack, low dynamic pressure initial conditions, and susceptibility to winds. A remotely piloted approach employing high-end hobbyist radio controlled (R/C) hardware was used for the powered demonstrator. This approach accommodated the interaction between the R/C flight system and the research flight control computer, engaging the L2F algorithm at varying initial conditions and artificially reducing the aircraft stability to stress the algorithm

Differential expression of prognostic proteomic markers in primary tumour, venous tumour thrombus and metastatic renal cell cancer tissue and correlation with patient outcome.

Renal cell carcinoma (RCC) is the most deadly of urological malignancies. Metastatic disease affects one third of patients at diagnosis with a further third developing metastatic disease after extirpative surgery. Heterogeneity in the clinical course ensures predicting metastasis is notoriously difficult, despite the routine use of prognostic clinico-pathological parameters in risk stratification. With greater understanding of pathways involved in disease pathogenesis, a number of biomarkers have been shown to have prognostic significance, including Ki67, p53, vascular endothelial growth factor receptor 1 (VEGFR1) and ligand D (VEGFD), SNAIL and SLUG. Previous pathway analysis has been from study of the primary tumour, with little attention to the metastatic tumours which are the focus of targeted molecular therapies. As such, in this study a tissue microarray from 177 patients with primary renal tumour, renal vein tumour thrombus and/or RCC metastasis has been created and used with Automated Quantitative Analysis (AQUA) of immunofluorescence to study the prognostic significance of these markers in locally advanced and metastatic disease. Furthermore, this has allowed assessment of differential protein expression between the primary tumours, renal vein tumour thrombi and metastases. The results demonstrate that clinico-pathological parameters remain the most significant predictors of cancer specific survival; however, high VEGFR1 or VEGFD can predict poor cancer specific survival on univariate analysis for locally advanced and metastatic disease. There was significantly greater expression of Ki67, p53, VEGFR1, SLUG and SNAIL in the metastases compared with the primary tumours and renal vein tumour thrombi. With the exception of p53, these differences in protein expression have not been shown previously in RCC. This confirms the importance of proliferation, angiogenesis and epithelial to mesenchymal transition in the pathogenesis and metastasis of RCC. Importantly, this work highlights the need for further pathway analysis of metastatic tumours for overcoming drug resistance and developing new therapies

The use of automated quantitative analysis to evaluate epithelial-to-mesenchymal transition associated proteins in clear cell renal cell carcinoma.

BACKGROUND: Epithelial-to-mesenchymal transition (EMT) has recently been implicated in the initiation and progression of renal cell carcinoma (RCC). Some mRNA gene expression studies have suggested a link between the EMT phenotype and poorer clinical outcome from RCC. This study evaluated expression of EMT-associated proteins in RCC using in situ automated quantitative analysis immunofluorescence (AQUA) and compared expression levels with clinical outcome. METHODS/PRINCIPAL FINDINGS: Unsupervised hierarchical cluster analysis of pre-existing RCC gene expression array data (GSE16449) from 36 patients revealed the presence of an EMT transcriptional signature in RCC [E-cadherin high/SLUG low/SNAIL low]. As automated immunofluorescence technology is dependent on accurate definition of the tumour cells in which measurements take place is critical, extensive optimisation was carried out resulting in a novel pan-cadherin based tumour mask that distinguishes renal cancer cells from stromal components. 61 patients with ccRCC and clinical follow-up were subsequently assessed for expression of EMT-associated proteins (WT1, SNAIL, SLUG, E-cadherin and phospho-β-catenin) on tissue microarrays. Using Kaplan-Meier analysis both SLUG (p = 0.029) and SNAIL (p = 0.024) (log rank Mantel-Cox) were significantly associated with prolonged progression free survival (PFS). Using Cox regression univariate and multivariate analysis none of the biomarkers were significantly correlated with outcome. 14 of the 61 patients expressed the gene expression analysis predicted EMT-protein signature [E-cadherin high/SLUG low/SNAIL low], which was not found to be associated to PFS when measured at the protein level. A combination of high expression of SNAIL and low stage was able to stratify patients with greater significance (p = 0.001) then either variable alone (high SNAIL p = 0.024, low stage p = 0.029). CONCLUSIONS: AQUA has been shown to have the potential to identify EMT related protein targets in RCC allowing for stratification of patients into high and low risk groups, as well the ability to assess the association of reputed EMT signatures to progression of the disease

Aircraft Configured for Flight in an Atmosphere Having Low Density

An aircraft is configured for flight in an atmosphere having a low density. The aircraft includes a fuselage, a pair of wings, and a rear stabilizer. The pair of wings extends from the fuselage in opposition to one another. The rear stabilizer extends from the fuselage in spaced relationship to the pair of wings. The fuselage, the wings, and the rear stabilizer each present an upper surface opposing a lower surface. The upper and lower surfaces have X, Y, and Z coordinates that are configured for flight in an atmosphere having low density

Methane emissions from oil and gas platforms in the North Sea

Since 1850 the concentration of atmospheric methane (CH4), a potent greenhouse gas, has more than doubled. Recent studies suggest that emission inventories may be missing sources and underestimating emissions. To investigate whether offshore oil and gas platforms leak CH4 during normal operation, we measured CH4 mole fractions around eight oil and gas production platforms in the North Sea which were neither flaring gas nor offloading oil. We use the measurements from summer 2017, along with meteorological data, in a Gaussian plume model to estimate CH4 emissions from each platform. We find CH4 mole fractions of between 11 and 370 ppb above background concentrations downwind of the platforms measured, corresponding to a median CH4 emission of 6.8 g CH4 s−1 for each platform, with a range of 2.9 to 22.3 g CH4 s−1. When matched to production records, during our measurements individual platforms lost between 0.04 % and 1.4 % of gas produced with a median loss of 0.23 %. When the measured platforms are considered collectively (i.e. the sum of platforms' emission fluxes weighted by the sum of the platforms' production), we estimate the CH4 loss to be 0.19 % of gas production. These estimates are substantially higher than the emissions most recently reported to the National Atmospheric Emission Inventory (NAEI) for total CH4 loss from United Kingdom platforms in the North Sea. The NAEI reports CH4 losses from the offshore oil and gas platforms we measured to be 0.13 % of gas production, with most of their emissions coming from gas flaring and offshore oil loading, neither of which was taking place at the time of our measurements. All oil and gas platforms we observed were found to leak CH4 during normal operation, and much of this leakage has not been included in UK emission inventories. Further research is required to accurately determine total CH4 leakage from all offshore oil and gas operations and to properly include the leakage in national and international emission inventories

Remote Sensing and Skywave Digital Communication from Antarctica

This paper presents an overview of the research activities undertaken by La Salle and the Ebro Observatory in the field of remote sensing. On 2003 we started a research project with two main objectives: implement a long-haul oblique ionospheric sounder and transmit the data from remote sensors located at the Spanish Antarctic station Juan Carlos I to Spain. The paper focuses on a study of feasibility of two possible physical layer candidates for the skywave link between both points. A DS-SS based solution and an OFDM based solution are considered to achieve a reliable low-power low-rate communication system between Antarctica and Spain

The Efficacy of Sunitinib Treatment of Renal Cancer Cells Is Associated with the Protein PHAX In Vitro

Anti-angiogenic agents, such as the multi-tyrosine kinase inhibitor sunitinib, are key first line therapies for metastatic clear cell renal cell carcinoma (ccRCC), but their mechanism of action is not fully understood. Here, we take steps towards validating a computational prediction based on differential transcriptome network analysis that phosphorylated adapter RNA export protein (PHAX) is associated with sunitinib drug treatment. The regulatory impact factor differential network algorithm run on patient tissue samples suggests PHAX is likely an important regulator through changes in genome-wide network connectivity. Immunofluorescence staining of patient tumours showed strong localisation of PHAX to the microvasculature consistent with the anti-angiogenic effect of sunitinib. In normal kidney tissue, PHAX protein abundance was low but increased with tumour grade (G1 vs. G3/4; p 0.01), consistent with a possible role in cancer progression. In organ culture, ccRCC cells had higher levels of PHAX protein expression than normal kidney cells, and sunitinib increased PHAX protein expression in a dose dependent manner (untreated vs. 100 µM; p 0.05). PHAX knockdown in a ccRCC organ culture model impacted the ability of sunitinib to cause cancer cell death (p 0.0001 untreated vs. treated), suggesting a role for PHAX in mediating the efficacy of sunitinib

The Consensus Coding Sequence (Ccds) Project: Identifying a Common Protein-Coding Gene Set for the Human and Mouse Genomes

Effective use of the human and mouse genomes requires reliable identification of genes and their products. Although multiple public resources provide annotation, different methods are used that can result in similar but not identical representation of genes, transcripts, and proteins. The collaborative consensus coding sequence (CCDS) project tracks identical protein annotations on the reference mouse and human genomes with a stable identifier (CCDS ID), and ensures that they are consistently represented on the NCBI, Ensembl, and UCSC Genome Browsers. Importantly, the project coordinates on manually reviewing inconsistent protein annotations between sites, as well as annotations for which new evidence suggests a revision is needed, to progressively converge on a complete protein-coding set for the human and mouse reference genomes, while maintaining a high standard of reliability and biological accuracy. To date, the project has identified 20,159 human and 17,707 mouse consensus coding regions from 17,052 human and 16,893 mouse genes. Three evaluation methods indicate that the entries in the CCDS set are highly likely to represent real proteins, more so than annotations from contributing groups not included in CCDS. The CCDS database thus centralizes the function of identifying well-supported, identically-annotated, protein-coding regions.National Human Genome Research Institute (U.S.) (Grant number 1U54HG004555-01)Wellcome Trust (London, England) (Grant number WT062023)Wellcome Trust (London, England) (Grant number WT077198

The Met Office Unified Model Global Atmosphere 6.0/6.1 and JULES Global Land 6.0/6.1 configurations

We describe Global Atmosphere 6.0 and Global Land 6.0: the latest science configurations of the Met Office Unified Model and JULES land surface model developed for use across all timescales. Global Atmosphere 6.0 includes the ENDGame dynamical core, which significantly increases mid-latitude variability improving a known model bias. Alongside developments of the model’s physical parametrisations, ENDGame also increases variability in the tropics, which leads to an improved representation of tropical cyclones and other tropical phenomena. Further developments of the atmospheric and land surface parametrisations improve other aspects of model performance, including the forecasting of surface weather phenomena. We also describe Global Atmosphere 6.1 and Global Land 6.1, which include a small number of long-standing differences from our main trunk configurations that we continue to require for operational global weather prediction. Since July 2014, GA6.1/GL6.1 has been used by the Met Office for operational global NWP, whilst GA6.0/GL6.0 was implemented in its remaining global prediction systems over the following year