Progressive lung cancer determined by expression profiling and transcriptional regulation

Clinically, our ability to predict disease outcome for patients with early stage lung cancer is currently poor. To address this issue, tumour specimens were collected at surgery from non-small cell lung cancer (NSCLC) patients as part of the European Early Lung Cancer (EUELC) consortium. The patients were followed-up for three years post-surgery and patients who suffered progressive disease (PD, tumour recurrence, metastasis or a second primary) or remained disease-free (DF) during follow-up were identified. RNA from both tumour and adjacent-normal lung tissue was extracted from patients and subjected to microarray expression profiling. These samples included 36 adenocarcinomas and 23 squamous cell carcinomas from both PD and DF patients. The microarray data was subject to a series of systematic bioinformatics analyses at gene, network and transcription factor levels. The focus of these analyses was 2-fold: firstly to determine whether there were specific biomarkers capable of differentiating between PD and DF patients, and secondly, to identify molecular networks which may contribute to the progressive tumour phenotype. The experimental design and analyses performed permitted the clear differentiation between PD and DF patients using a set of biomarkers implicated in neuroendocrine signalling and allowed the inference of a set of transcription factors whose activity may differ according to disease outcome. Potential links between the biomarkers, the transcription factors and the genes p21/CDKN1A and Myc, which have previously been implicated in NSCLC development, were revealed by a combination of pathway analysis and microarray meta-analysis. These findings suggest that neuroendocrine-related genes, potentially driven through p21/CDKN1A and Myc, are closely linked to whether or not a NSCLC patient will have poor clinical outcome.

Profiling excretory/secretory proteins of Trichinella spiralis muscle larvae by two-dimensional gel electrophoresis and mass spectrometry

Infection of mammalian skeletal muscle with the intracellular parasite Trichinella spiralis results in profound alterations in the host cell and a realignment of host cell gene expression. The role of parasite excretory/secretory (E/S) products in mediating these effects is unknown, largely due to the difficulty in identifying and assigning function to individual proteins. In this study, we have used two-dimensional electrophoresis to analyse the profile of muscle larva excreted/secreted proteins and have coupled this to protein identification using MALDI-TOF mass spectrometry. Interpretation of the peptide mass fingerprint data has relied primarily on the interrogation of a custom-made Trichinella EST database and the NemaGene cluster database for T. spiralis. Our results suggest that this proteomic approach is a useful tool to study protein expression in Trichinella spp. and will contribute to the identification of excreted/secreted proteins.

PCB congener dynamics in a heavily industrialized river catchment

PCB congener concentrations in the water column of a highly industrialized river catchment, the Aire/Calder, in N.E. England were determined weekly on a routine basis, and 2 hourly through selected high flow (flood) events. Bed, suspended and floodplain sediment PCB congener concentrations were also determined along transects of the rivers investigated. Weekly monitoring revealed that the sum of 11 quantified (Sigma11) PCBs rose in concentration by two orders of magnitude during late summer compared to their winter minimum values. This rise was concurrent with sustained periods of low flow. SigmaPCB concentrations were rapidly diluted during high flow (flood) events. Suspended sediment was, on average, 13 times more contaminated with PCBs than bed sediment, with means of 4.0 and 53.8 ng/g, respectively, while floodplain samples had an intermediate concentration of 29.8 ng/g. Principle components analysis (PCA) of congener profiles showed that all three sediment types were similar, but that congener profiles differed considerably between sediment and whole-water samples. There was no change in the percentage contribution of individual PCB congeners apparent from weekly whole-water monitoring. However, the congener pattern in whole-waters changed systematically during high flow events. PCA showed that whole-water samples collected during high flow events had progressively more sediment characteristics, and then returned to whole-water characteristics on cessation of the event. The PCA evidence, dilution of PCB concentrations during events, and suspended sediments more contaminated than bed sediments, indicate that the major sources of PCBs in this catchment are current inputs from sewage treatment works, rather than remobilization of bed sediments.

Transient distributions of composition and temperature in a gas-solid packed bed reactor by near-infrared tomography

Near-infrared diffuse tomography was used in order to observe dynamic behaviour of flowing gases by measuring the 3D distributions of composition and temperature in a weakly scattering packed bed reactor, subject to wall effects and non-isothermal conditions. The technique was applied to the vapour phase hydrogen isotopic exchange reaction in a hydrophobic packing of low aspect ratio made of platinum on styrene divinyl benzene sulphonate copolymer resin. The results of tomography revealed uneven temperature and composition maps of water and deuterated water vapours in the core-packed bed and in the vicinity of the wall owing to flow maldistribution. The dynamic lag between the near-wall water vapour and deuterated water vapour compositions were observed suggesting that the convective transfer which was significant near the wall at the start, owing to high porosity, was also effective at large conversions. (C) 2012 Elsevier B.V. All rights reserved.

Hormone profiling in a novel enteroendocrine cell line pGIP/neo:STC-1

GIP is a peptide hormone of therapeutic interest in type 2 diabetes and obesity. This study evaluated pGIP/neo STC-1 as a potential K-cell model for studying GIP secretion.

Source as a controlling factor on the quality and interpretation of sediment magnetic records from the northern North Atlantic

Magnetic properties of eight particle size ranges from nine locations in Iceland and 26 locations in southern Greenland reveal the importance of source variation for our understanding of paleomagnetic and environmental magnetic records in the marine environment. These terrestrial samples show varying degrees of particle size dependence with all samples showing that the silt fraction possesses greater concentrations of ferrimagnetic minerals than either clay or sand. Fine pseudo-single domain (PSD) size magnetic grains dominate the magnetic assemblage of all Icelandic fractions. In contrast, Greenlandic samples possess greater variation in magnetic grain size; only fine silt and clay are as magnetically fine as the Icelandic PSD grains, while Greenlandic silts and sands are dominated by coarser PSD and multi-domain grains. These observations from potential marine sediment sources suggest that the silt size fraction is a likely driver for much of the concentration-dependent parameters derived from bulk magnetic records and that the magnetic grain size of the silt fraction can be used to discriminate between Icelandic and Greenlandic sources. Using these results to examine magnetic grain size records from marine sediment cores collected across the northern North Atlantic suggests that source, not just transport-controlled physical grain-size, has a significant impact on determining the magnetic grain size at a particular location. Homogeneity of magnetic grain size in Icelandic sediments at least partially explains the consistent quality of paleomagnetic records derived from cores surrounding Iceland and their ability to buffer large environmental changes. © 2013 Elsevier B.V.

An in situ spatially resolved method to probe gas phase reactions through a fixed bed catalyst

A new method to spatially probe heterogeneous catalysed reactions within a packed bed of catalyst has been developed. The spatial resolution is achieved using a stationary perforated capillary coupled to a mass spectrometer while the catalyst bed is moved. The oxidation of CO promoted by H-2 over a Pd catalyst has been used to demonstrate the technique.

An in situ spatially resolved analytical technique to simultaneously probe gas phase reactions and temperature within the packed bed of a plug flow reactor

This paper reports the detailed description and validation of a fully automated, computer controlled analytical method to spatially probe the gas composition and thermal characteristics in packed bed systems. As an exemplar, we have examined a heterogeneously catalysed gas phase reaction within the bed of a powdered oxide supported metal catalyst. The design of the gas sampling and the temperature recording systems are disclosed. A stationary capillary with holes drilled in its wall and a moveable reactor coupled with a mass spectrometer are used to enable sampling and analysis. This method has been designed to limit the invasiveness of the probe on the reactor by using the smallest combination of thermocouple and capillary which can be employed practically. An 80 mu m (O.D.) thermocouple has been inserted in a 250 mu m (O.D.) capillary. The thermocouple is aligned with the sampling holes to enable both the gas composition and temperature profiles to be simultaneously measured at equivalent spatially resolved positions. This analysis technique has been validated by studying CO oxidation over a 1% Pt/Al2O3 catalyst and the spatial resolution profiles of chemical species concentrations and temperature as a function of the axial position within the catalyst bed are reported.

Profiling the ionome of rice and its use in discriminating geographical origins at the regional scale, China

Element profile was investigated for their use to trace the geographical origin of rice (Oryza sativa L.) samples. The concentrations of 13 elements (calcium (Ca), potassium (K), magnesium (Mg), phosphorus (P), boron (B), manganese (Mn), iron (Fe), nickel (Ni), copper (Cu), arsenic (As), selenium (Se), molybdenum (Mo), and cadmium (Cd)) were determined in the rice samples by inductively coupled plasma optical emission and mass spectrometry. Most of the essential elements for human health in rice were within normal ranges except for Mo and Se. Mo concentrations were twice as high as those in rice from Vietnam and Spain. Meanwhile, Se concentrations were three times lower in the whole province compared to the Chinese average level of 0.088 mg/kg. About 12% of the rice samples failed the Chinese national food safety standard of 0.2 mg/kg for Cd. Combined with the multi-elemental profile in rice, the principal component analysis (PCA), discriminant function analysis (DFA) and Fibonacci index analysis (FIA) were applied to discriminate geographical origins of the samples. Results indicated that the FIA method could achieve a more effective geographical origin classification compared with PCA and DFA, due to its efficiency in making the grouping even when the elemental variability was so high that PCA and DFA showed little discriminatory power. Furthermore, some elements were identified as the most powerful indicators of geographical origin: Ca, Ni, Fe and Cd. This suggests that the newly established methodology of FIA based on the ionome profile can be applied to determine the geographical origin of rice.

Predicting critical source areas of sediment in headwater catchments

Mitigation of diffuse nutrient and sediment delivery to streams requires successful identification andmanagement of critical source areas within catchments. Approaches to predicting high risk areas forsediment loss have typically relied on structural drivers of connectivity and risk, with little considera-tion given to process driven water quality responses. To assess the applicability of structural metrics topredict critical source areas, geochemical tracing of land use sources was conducted in three headwateragricultural catchments in Co. Down and Co. Louth, Ireland, within a Monte Carlo framework. Outputswere applied to the inverse optimisation of a connectivity model, based on LiDAR DEM data, to assess theefficacy of land use risk weightings to predict sediment source contributions over the 18 month studyperiod in the Louth Upper, Louth Lower and Down catchments. Results of the study indicated sedimentproportions over the study period varied from 6 to 10%, 84 to 87%, 4%, and 2 to 3% for the Down Catch-ment, 79 to 85%, 9 to 17%, 1 to 3% and 2 to 3% in the Louth Upper and 2 to 3%, 79 to 85%, 10 to 17%and 2 to 3% in the Louth Lower for arable, channel bank, grassland, and woodland sources, respectively.Optimised land use risk weightings for each sampling period showed that at the larger catchment scale,no variation in median land use weightings were required to predict land use contributions. However,for the two smaller study catchments, variation in median risk weightings was considerable, which mayindicate the importance of functional connectivity processes at this spatial scale. In all instances, arableland consistently generated the highest risk of sediment loss across all catchments and sampling times.This study documents some of the first data on sediment provenance in Ireland and indicates the needfor cautious consideration of land use as a tool to predict critical source areas at the headwater scale