N-nitroso compound exposure-associated transcriptomic profiles are indicative of an increased risk for colorectal cancer

Endogenous formation of N-nitroso compounds (NOCs), which are known animal carcinogens, could contribute to human carcinogenesis but definitive evidence is still lacking. To investigate the relevance of NOCs in human colorectal cancer (CRC) development, we analyzed whole genome gene expression modifications in human colon biopsies in relation to fecal NOC exposure. We had a particular interest in patients suffering from intestinal inflammation as this may stimulate endogenous NOC formation, and consequently predispose to CRC risk. Inflammatory bowel disease (IBD) patients diagnosed with ulcerative colitis and irritable bowel syndrome patients without inflammation, serving as controls, were therefore recruited. Fecal NOC were demonstrated in the majority of subjects. By associating gene expression levels of all subjects to fecal NOC levels, we identified a NOC exposure-associated transcriptomic response that suggests that physiological NOC concentrations may potentially induce genotoxic responses and chromatin modifications in human colon tissue, both of which are linked to carcinogenicity. In a network analysis, chromatin modifications were linked to 11 significantly modulated histone genes, pointing towards a possible epigenetic mechanism that may be relevant in comprehending NOC-induced carcinogenesis. In addition, pro-inflammatory transcriptomic modifications were identified in visually non-inflamed regions of the IBD colon. However, fecal NOC levels were slightly but not significantly increased in IBD patients, suggesting that inflammation did not strongly stimulate NOC formation. We conclude that NOC exposure is associated with gene expression modifications in the human colon that may suggest a potential role of these compounds in CRC development.

Synthesis and glycosidase inhibitory profiles of functionalised morpholines and oxazepanes

In this work libraries of morpholines and oxazepanes have been prepared via the reductive amination reaction between dialdehydes, derived from carbohydrates, and a range of amines. In this way, functionalised morpholines and oxazepanes have been prepared that include N-alkylated derivatives, disaccharide analogues, and ester containing derivatives. The abilities of these functionalised morpholines and oxazepanes to inhibit a broad panel of glycosidase enzymes, that are associated with a range of diseases, have been probed and in this way new inhibitors of a range of glycosidases, but particularly β-d-galactosidase derived from Bovine kidney, have been discovered. N-Alkyl morpholines demonstrated the best inhibition profiles for this enzyme and derivatives (15a)–(15d) acted as non-competitive inhibitors with IC50 values of 55.1–88.6 μM. Within this study, some preliminary structure–activity relationships are proposed, and it is demonstrated that N-substituted morpholines display better inhibitory profiles for the enzymes analysed than any of the N-substituted oxazepanes.

Normality mining: privacy implications of behavioral profiles drawn from GPS enabled mobile phones

There is growing interest in the ways in which the location of a person can be utilized by new applications and services. Recent advances in mobile technologies have meant that the technical capability to record and transmit location data for processing is appearing in off-the-shelf handsets. This opens possibilities to profile people based on the places they visit, people they associate with, or other aspects of their complex routines determined through persistent tracking. It is possible that services offering customized information based on the results of such behavioral profiling could become commonplace. However, it may not be immediately apparent to the user that a wealth of information about them, potentially unrelated to the service, can be revealed. Further issues occur if the user agreed, while subscribing to the service, for data to be passed to third parties where it may be used to their detriment. Here, we report in detail on a short case study tracking four people, in three European member states, persistently for six weeks using mobile handsets. The GPS locations of these people have been mined to reveal places of interest and to create simple profiles. The information drawn from the profiling activity ranges from intuitive through special cases to insightful. In this paper, these results and further extensions to the technology are considered in light of European legislation to assess the privacy implications of this emerging technology.

A combined engineering and statistical model of UK domestic appliance electrical load profiles

The development of a combined engineering and statistical Artificial Neural Network model of UK domestic appliance load profiles is presented. The model uses diary-style appliance use data and a survey questionnaire collected from 51 suburban households and 46 rural households during the summer of 2010 and2011 respectively. It also incorporates measured energy data and is sensitive to socioeconomic, physical dwelling and temperature variables. A prototype model is constructed in MATLAB using a two layer feed forward network with back propagation training which has a 12:10:24 architecture. Model outputs include appliance load profiles which can be applied to the fields of energy planning (microrenewables and smart grids), building simulation tools and energy policy.

A novel satellite mission concept for upper air water vapour, aerosol and cloud observations using integrated path differential absorption LiDAR limb sounding

We propose a new satellite mission to deliver high quality measurements of upper air water vapour. The concept centres around a LiDAR in limb sounding by occultation geometry, designed to operate as a very long path system for differential absorption measurements. We present a preliminary performance analysis with a system sized to send 75 mJ pulses at 25 Hz at four wavelengths close to 935 nm, to up to 5 microsatellites in a counter-rotating orbit, carrying retroreflectors characterized by a reflected beam divergence of roughly twice the emitted laser beam divergence of 15 µrad. This provides water vapour profiles with a vertical sampling of 110 m; preliminary calculations suggest that the system could detect concentrations of less than 5 ppm. A secondary payload of a fairly conventional medium resolution multispectral radiometer allows wide-swath cloud and aerosol imaging. The total weight and power of the system are estimated at 3 tons and 2,700 W respectively. This novel concept presents significant challenges, including the performance of the lasers in space, the tracking between the main spacecraft and the retroreflectors, the refractive effects of turbulence, and the design of the telescopes to achieve a high signal-to-noise ratio for the high precision measurements. The mission concept was conceived at the Alpbach Summer School 2010.

Receptor binding profiles of avian influenza virus hemagglutinin subtypes on human cells as a predictor of pandemic potential

The host adaptation of influenza virus is partly dependent on the sialic acid (SA) isoform bound by the viral hemagglutinin (HA). Avian influenza viruses preferentially bind the α-2,3 SA and human influenza viruses the α-2,6 isoform. Each isoform is predominantly associated with different surface epithelial cell types of the human upper airway. Using recombinant HAs and human tracheal airway epithelial cells in vitro and ex vivo, we show that many avian HA subtypes do not adhere to this canonical view of SA specificity. The propensity of avian viruses to adapt to human receptors may thus be more widespread than previously supposed.

An analytical model of mountain wave drag for wind profiles with shear and curvature

An analytical model is developed to predict the surface drag exerted by internal gravity waves on an isolated axisymmetric mountain over which there is a stratified flow with a velocity profile that varies relatively slowly with height. The model is linear with respect to the perturbations induced by the mountain, and solves the Taylor–Goldstein equation with variable coefficients using a Wentzel–Kramers–Brillouin (WKB) approximation, formally valid for high Richardson numbers, Ri. The WKB solution is extended to a higher order than in previous studies, enabling a rigorous treatment of the effects of shear and curvature of the wind profile on the surface drag. In the hydrostatic approximation, closed formulas for the drag are derived for generic wind profiles, where the relative magnitude of the corrections to the leading-order drag (valid for a constant wind profile) does not depend on the detailed shape of the orography. The drag is found to vary proportionally to Ri21, decreasing as Ri decreases for a wind that varies linearly with height, and increasing as Ri decreases for a wind that rotates with height maintaining its magnitude. In these two cases the surface drag is predicted to be aligned with the surface wind. When one of the wind components varies linearly with height and the other is constant, the surface drag is misaligned with the surface wind, especially for relatively small Ri. All these results are shown to be in fairly good agreement with numerical simulations of mesoscale nonhydrostatic models, for high and even moderate values of Ri.

Non-concordance between genetic profiles of olive oil and fruit: a cautionary note to the use of DNA markers for provenance testing.

To investigate the contribution of paternal alleles to the DNA content of olive oil, genetic analyses of olive DNA samples from fruits, leaves, and oil derived from the same tree (cv. Leccino) were carried out. DNA extracted from maternal tissues--leaves and flesh--from different fruits showed identical genetic profiles using a set of DNA markers. Additional simple sequence repeat (SSR) alleles, not found in the maternal samples, were amplified in the embryos (stone), and they were also detected in DNA extracted from the paste obtained by crushing whole fruits and from the oil pressed from this material. These results demonstrate that the DNA profile obtained from olive oil is likely to represent a composite profile of the maternal alleles juxtaposed with alleles contributed by various pollen donors. Therefore, care needs to be taken in the interpretation of DNA profiles obtained from DNA extracted from oil for resolving provenance and authenticity issues.

An assessment of a three-beam Doppler lidar wind profiling method for use in urban areas

Currently there are few observations of the urban wind field at heights other than rooftop level. Remote sensing instruments such as Doppler lidars provide wind speed data at many heights, which would be useful in determining wind loadings of tall buildings, and predicting local air quality. Studies comparing remote sensing with traditional anemometers carried out in flat, homogeneous terrain often use scan patterns which take several minutes. In an urban context the flow changes quickly in space and time, so faster scans are required to ensure little change in the flow over the scan period. We compare 3993 h of wind speed data collected using a three-beam Doppler lidar wind profiling method with data from a sonic anemometer (190 m). Both instruments are located in central London, UK; a highly built-up area. Based on wind profile measurements every 2 min, the uncertainty in the hourly mean wind speed due to the sampling frequency is 0.05–0.11 m s−1. The lidar tended to overestimate the wind speed by ≈0.5 m s−1 for wind speeds below 20 m s−1. Accuracy may be improved by increasing the scanning frequency of the lidar. This method is considered suitable for use in urban areas.

Graph-based algorithms for comparison and prediction of household-level energy use profiles

We present an efficient graph-based algorithm for quantifying the similarity of household-level energy use profiles, using a notion of similarity that allows for small time–shifts when comparing profiles. Experimental results on a real smart meter data set demonstrate that in cases of practical interest our technique is far faster than the existing method for computing the same similarity measure. Having a fast algorithm for measuring profile similarity improves the efficiency of tasks such as clustering of customers and cross-validation of forecasting methods using historical data. Furthermore, we apply a generalisation of our algorithm to produce substantially better household-level energy use forecasts from historical smart meter data.

Effect of provenance, plant part and processing on extract profiles from cultivated European Rhodiola rosea L. for medicinal use.

The demand for plant material of Rhodiola rosea L. (Crassulaceae) for medicinal use has increased recently, amid concerns about its quality and sustainability. We have analysed the content of phenylpropanoids (total rosavins) and salidroside in liquid extracts from 3-year old cultivated plants of European origin, and mapped the influence of plant part (rhizome versus root), genotype, drying, cutting, and extraction solvent to chemical composition. Rhizomes contained 1.5-4 times more salidroside (0.3-0.4% dry wt) and total rosavins (1.2-3.0%) than roots. The qualitative decisive phenylpropanoid content in the extracts was most influenced by plant part, solvent, and genotype, while drying temperature and cutting conditions were of less importance. We have shown that R. rosea from different boreal European provenances can be grown under temperate conditions and identified factors to obtain consistent high quality extracts provided that authentic germplasm is used and distinguished between rhizome, roots and their mixtures.

Observations of wind speed profiles over Greater London, UK, using a Doppler lidar

To calculate the potential wind loading on a tall building in an urban area, an accurate representation of the wind speed profile is required. However, due to a lack of observations, wind engineers typically estimate the characteristics of the urban boundary layer by translating the measurements from a nearby reference rural site. This study presents wind speed profile data obtained from a Doppler lidar in central London, UK, during an 8 month observation period. Used in conjunction with wind speed data measured at a nearby airport, the data have been used to assess the accuracy of the predictions made by the wind engineering tools currently available. When applied to multiple changes in surface roughness identified from morphological parameters, the non-equilibrium wind speed profile model developed by Deaves (1981) provides a good representation of the urban wind speed profile. For heights below 500 m, the predicted wind speed remains within the 95% confidence interval of the measured data. However, when the surface roughness is estimated using land use as a proxy, the model tends to overestimate the wind speed, particularly for very high wind speed periods. These results highlight the importance of a detailed assessment of the nature of the surface when estimating the wind speed above an urban surface.

Black carbon vertical profiles strongly affect its radiative forcing uncertainty

The impact of black carbon (BC) aerosols on the global radiation balance is not well constrained. Here twelve global aerosol models are used to show that at least 20% of the present uncertainty in modeled BC direct radiative forcing (RF) is due to diversity in the simulated vertical profile of BC mass. Results are from phases 1 and 2 of the global aerosol model intercomparison project (AeroCom). Additionally, a significant fraction of the variability is shown to come from high altitudes, as, globally, more than 40% of the total BC RF is exerted above 5 km. BC emission regions and areas with transported BC are found to have differing characteristics. These insights into the importance of the vertical profile of BC lead us to suggest that observational studies are needed to better characterize the global distribution of BC, including in the upper troposphere.

Cannabidivarin-rich cannabis extracts are anticonvulsant in mouse and rat via a CB 1 receptor-independent mechanism

BACKGROUND AND PURPOSE Epilepsy is the most prevalent neurological disease and is characterized by recurrent seizures. Here, we investigate (i) the anticonvulsant profiles of cannabis-derived botanical drug substances (BDSs) rich in cannabidivarin (CBDV) and containing cannabidiol (CBD) in acute in vivo seizure models and (ii) the binding of CBDV BDSs and their components at cannabinoid CB 1 receptors. EXPERIMENTAL APPROACH The anticonvulsant profiles of two CBDV BDSs (50–422 mg·kg −1 ) were evaluated in three animal models of acute seizure. Purified CBDV and CBD were also evaluated in an isobolographic study to evaluate potential pharmacological interactions. CBDV BDS effects on motor function were also investigated using static beam and grip strength assays. Binding of CBDV BDSs to cannabinoid CB 1 receptors was evaluated using displacement binding assays. KEY RESULTS CBDV BDSs exerted significant anticonvulsant effects in the pentylenetetrazole (≥100 mg·kg −1 ) and audiogenic seizure models (≥87 mg·kg −1 ), and suppressed pilocarpine-induced convulsions (≥100 mg·kg −1 ). The isobolographic study revealed that the anticonvulsant effects of purified CBDV and CBD were linearly additive when co-administered. Some motor effects of CBDV BDSs were observed on static beam performance; no effects on grip strength were found. The Δ 9 -tetrahydrocannabinol and Δ 9 -tetrahydrocannabivarin content of CBDV BDS accounted for its greater affinity for CB 1 cannabinoid receptors than purified CBDV. CONCLUSIONS AND IMPLICATIONS CBDV BDSs exerted significant anticonvulsant effects in three models of seizure that were not mediated by the CB 1 cannabinoid receptor and were of comparable efficacy with purified CBDV. These findings strongly support the further clinical development of CBDV BDSs for the treatment of epilepsy.