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.

Intelligent methods for load forecasting

Load forecasting is an important task in the management of a power utility. The most recent developments in forecasting involve the use of artificial intelligence techniques, which offer powerful modelling capabilities. This paper discusses these techniques and provides a review of their application to load forecasting.

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.

Tephra fallout hazard assessment for a Plinian eruption scenario at Volcán de Colima (Mexico)

Volcanic ash fallout associated with renewal of explosive activity at Colima, represents a serious threat to the surrounding urbanized area. Here we assess the tephra fallout hazard associated with a Plinian eruption scenario. The eruptive history of Volcán de Colima shows that Plinian eruptions occur approximately every 100 years and the last eruption, the 1913, represents the largest historic eruption of this volcano. We used the last eruption as a reference to discuss volcanic hazard and risk scenarios connected with ash fallout. Tephra fallout deposits are modeled using HAZMAP, a model based on a semi-analytical solution of the advection– diffusion–sedimentation equation for volcanic particles. Based on a statistical study of wind profiles at Colima region, we first reconstructed ash loading maps and then computed ground load probability maps for different seasons. The obtained results show that a Plinian eruptive scenario at Volcán de Colima, could seriously damage more than 10 small towns and ranches, and potentially affect big cities located at tens of kilometers from the eruptive center. The probability maps obtained are aimed to give support to the risk mitigation strategies

The impact of catechol-O-methyltransferase genotype on the acute responsiveness of vascular reactivity to a green tea extract

The beneficial effects of green tea catechins, such as the proposed improvement in endothelial function, may be influenced by phase II metabolism during and after absorption. The methylation enzyme, catechol-O-methyltransferase (COMT), has a missense mutation rs4680 (G to A), proposed to result in a 40 % reduction in enzyme activity. In the present pilot study, twenty subjects (ten of each homozygous COMT genotype) were recruited. Green tea extract capsules (836 mg green tea catechins) were given in a fasted state, and a high-carbohydrate breakfast was given after 60 min. Blood samples and vascular function measurements were taken at regular intervals. The change in digital volume pulse stiffness index (SI) from baseline was shown to be different between genotype groups at 120 and 240 min, with a lower SI in the GG individuals (P ≤ 0·044). The change in blood pressure from baseline also differed between genotype groups, with a greater increase in systolic (P = 0·023) and diastolic (P = 0·034) blood pressure at 120 min in the GG group. The AA group was shown to have a greater increase in insulin concentrations at 120 min (P = 0·019) and 180 min (P = 0·008) compared with baseline, despite similar glucose profiles. No genotypic differences were found in vascular reactivity measured using laser Doppler iontophoresis, total nitrite, lipids, plasma total antioxidant capacity or inflammatory markers after ingestion of the green tea extract. In conclusion, SI and insulin response to the glucose load differed between the COMT genotype groups, and this may be suggestive of a green tea extract and genotype interaction.

Quantification of mitochondrial DNA mutation load

Mitochondrial DNA (mtDNA) mutations are an important cause of genetic disease and have been proposed to play a role in the ageing process. Quantification of total mtDNA mutation load in ageing tissues is difficult as mutational events are rare in a background of wild-type molecules, and detection of individual mutated molecules is beyond the sensitivity of most sequencing based techniques. The methods currently most commonly used to document the incidence of mtDNA point mutations in ageing include post-PCR cloning, single-molecule PCR and the random mutation capture assay. The mtDNA mutation load obtained by these different techniques varies by orders of magnitude, but direct comparison of the three techniques on the same ageing human tissue has not been performed. We assess the procedures and practicalities involved in each of these three assays and discuss the results obtained by investigation of mutation loads in colonic mucosal biopsies from ten human subjects.

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 method of formulating energy load profile for domestic buildings in the UK

There are varieties of physical and behavioral factors to determine energy demand load profile. The attainment of the optimum mix of measures and renewable energy system deployment requires a simple method suitable for using at the early design stage. A simple method of formulating load profile (SMLP) for UK domestic buildings has been presented in this paper. Domestic space heating load profile for different types of houses have been produced using thermal dynamic model which has been developed using thermal resistant network method. The daily breakdown energy demand load profile of appliance, domestic hot water and space heating can be predicted using this method. The method can produce daily load profile from individual house to urban community. It is suitable to be used at Renewable energy system strategic design stage.

Adaptive recursive control of a soil testing load frame

Recursive Learning Control (RLC) has the potential to significantly reduce the tracking error in many repetitive trajectory applications. This paper presents an application of RLC to a soil testing load frame where non-adaptive techniques struggle with the highly nonlinear nature of soil. The main purpose of the controller is to apply a sinusoidal force reference trajectory on a soil sample with a high degree of accuracy and repeatability. The controller uses a feedforward control structure, recursive least squares adaptation algorithm and RLC to compensate for periodic errors. Tracking error is reduced and stability is maintained across various soil sample responses.

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.