Modular digital holographic fringe data processing system

A software architecture suitable for reducing holographic fringe data into useful engineering data is developed and tested. The results, along with a detailed description of the proposed architecture for a Modular Digital Fringe Analysis System, are presented

Possible mechanism for achieving glass-like thermal conductivities in crystals with off-center atoms

In the filled Ga/Ge clathrate, Eu and Sr are off-center in site 2 but Ba is on-center. All three filler atoms (Ba,Eu,Sr) have low temperature Einstein modes; yet only for the Eu and Sr systems is there a large dip in the thermal conductivity, attributed to the Einstein modes. No dip is observed for Ba. Here we argue that it is the off-center displacement that is crucial for understanding this unexplained difference in behavior. It enhances the coupling between the "rattler" motion and the lattice phonons for the Eu and Sr systems, and turns on/off another scattering mechanism (for 1K < T < 20K) produced by the presence/absence of off-center sites. The random occupation of different off-center sites produces a high density of symmetry-breaking defects which scatters phonons. It may also be important for improving our understanding of other glassy systems.Comment: 4 pages, 1 figure (2 parts) -- v2: intro broadened; strengthened arguments regarding need for additional phonon scattering mechanis

The geomorphological setting of some of Scotland's east coast freshwater mills: a comment on Downward and Skinner (2005) ‘Working rivers: the geomorphological legacy...’

Many of the water mills on Scotland's east coast streams, unlike those discussed recently by Downward and Skinner (2005 Area 37 138–47), are found in predominantly bedrock reaches immediately downstream of knickpoints (i.e. bedrock steps). Bedrock knickpoints in the lower reaches of Scottish rivers are a widespread fluvial response to the glacio-isostatic rebound of northern Britain. These steps in the river profile propagate headward over time, but for intervals of a few centuries or so they are sufficiently stable to be exploited for the elevational fall necessary to power the mill wheel. Many of these mills were apparently powered by ‘run-of-the-river’, as are some today that formerly had mill dams. The typical lack of sediment storage along the erosional lower reaches of many Scottish rivers means that failure of mill structures in Scotland will probably have less dramatic geomorphological and management implications than those suggested by Downward and Skinner for southern English rivers

Guidelines for the use of cell lines in biomedical research

Cell-line misidentification and contamination with microorganisms, such as mycoplasma, together with instability, both genetic and phenotypic, are among the problems that continue to affect cell culture. Many of these problems are avoidable with the necessary foresight, and these Guidelines have been prepared to provide those new to the field and others engaged in teaching and instruction with the information necessary to increase their awareness of the problems and to enable them to deal with them effectively. The Guidelines cover areas such as development, acquisition, authentication, cryopreservation, transfer of cell lines between laboratories, microbial contamination, characterisation, instability and misidentification. Advice is also given on complying with current legal and ethical requirements when deriving cell lines from human and animal tissues, the selection and maintenance of equipment and how to deal with problems that may arise

Evaluation of epidermal growth factor receptors in bladder tumours.

Epidermal growth factor (EGF) receptor expression in 31 primary human bladder tumours was quantitated using both structural and functional assays and the EGF receptor gene in the same tumours was analyzed by Southern blot analysis. Immunocytochemical studies using the EGFR1 monoclonal antibody (Mab) showed a significant correlation between EGF receptor levels and the stage and grade of the tumours. Autophosphorylation assays employed to evaluate the receptor's tyrosine kinase activity gave results which in general were consistent with the immunocytochemical data. Using internally controlled immunocytochemical studies with two Mabs and Southern blot analysis of DNA isolated from the tumours, no evidence was obtained for the production of truncated receptors similar to those encoded by the v-erb-B oncogene. Gene amplification was not found in any of the superficial tumours, but one invasive tumour with high EGF receptor expression had an 8-10 fold amplification of the EGF receptor gene. The EGF receptor isolated from this tumour showed a normal pattern of tyrosine phosphorylation at all three major autophosphorylation sites. Our detailed study is consistent with the correlation previously found between EGF receptor expression and stage and grade of bladder tumours, and suggests that at this level of analysis EGF receptors in bladder tumours are not abnormal in structure or size, autophosphorylation activity, or gene structure

RAS signalling through PI3-Kinase controls cell migration via modulation of Reelin expression.

RAS signalling through phosphoinositide 3-kinase (PI3-Kinase) has been shown to have an essential role in tumour initiation and maintenance. RAS also regulates cell motility and tumour invasiveness, but the role of direct RAS binding to PI3-Kinase in this remains uncertain. Here, we provide evidence that disruption of RAS interaction with PI3-Kinase p110α decreases cell motility and prevents activation of Rac GTPase. Analysis of gene expression in cells lacking RAS interaction with p110α reveals increased levels of the extracellular matrix glycoprotein Reelin and activation of its downstream pathway resulting in upregulation of E-cadherin expression. Induction of the Reelin/E-cadherin axis is also observed in Kras mutant lung tumours that are regressing due to blockade of RAS interaction with PI3-Kinase. Furthermore, loss of Reelin correlates with decreased survival of lung and breast cancer patients. Reelin thus plays a role in restraining RAS and PI3-kinase promotion of cell motility and potentially tumour metastasis

The demand for sports and exercise: Results from an illustrative survey

Funding from the Department of Health policy research programme was used in this study.There is a paucity of empirical evidence on the extent to which price and perceived benefits affect the level of participation in sports and exercise. Using an illustrative sample of 60 adults at Brunel University, West London, we investigate the determinants of demand for sports and exercise. The data were collected through face-to-face interviews that covered indicators of sports and exercise behaviour; money/time price and perceived benefits of participation; and socio- economic/demographic details. Count, linear and probit regression models were fitted as appropriate. Seventy eight per cent of the sample participated in sports and exercise and spent an average of £27 per month and an average of 20 min travelling per occasion of sports and exercise. The demand for sport and exercise was negatively associated with time (travel or access time) and ‘variable’ price and positively correlated with ‘fixed’ price. Demand was price inelastic, except in the case of meeting the UK government’s recommended level of participation, which is time price elastic (elasticity = −2.2). The implications of data from a larger nationally representative sample as well as the role of economic incentives in influencing uptake of sports and exercise are discussed.This article is available through the Brunel Open Access Publishing Fund

RAS oncogenic activity predicts response to chemotherapy and outcome in lung adenocarcinoma.

Activating mutations in KRAS occur in 32% of lung adenocarcinomas (LUAD). Despite leading to aggressive disease and resistance to therapy in preclinical studies, the KRAS mutation does not predict patient outcome or response to treatment, presumably due to additional events modulating RAS pathways. To obtain a broader measure of RAS pathway activation, we developed RAS84, a transcriptional signature optimised to capture RAS oncogenic activity in LUAD. We report evidence of RAS pathway oncogenic activation in 84% of LUAD, including 65% KRAS wild-type tumours, falling into four groups characterised by coincident alteration of STK11/LKB1, TP53 or CDKN2A, suggesting that the classifications developed when considering only KRAS mutant tumours have significance in a broader cohort of patients. Critically, high RAS activity patient groups show adverse clinical outcome and reduced response to chemotherapy. Patient stratification using oncogenic RAS transcriptional activity instead of genetic alterations could ultimately assist in clinical decision-making

Efficient Genotyping of KRAS Mutant Non-Small Cell Lung Cancer Using a Multiplexed Droplet Digital PCR Approach

© 2015 Pender et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Droplet digital PCR (ddPCR) can be used to detect low frequency mutations in oncogenedriven lung cancer. The range of KRAS point mutations observed in NSCLC necessitates a multiplex approach to efficient mutation detection in circulating DNA. Here we report the design and optimisation of three discriminatory ddPCR multiplex assays investigating nine different KRAS mutations using PrimePCRddPCRMutation Assays and the Bio-Rad QX100 system. Together these mutations account for 95% of the nucleotide changes found in KRAS in human cancer. Multiplex reactions were optimised on genomic DNA extracted from KRAS mutant cell lines and tested on DNA extracted from fixed tumour tissue from a cohort of lung cancer patients without prior knowledge of the specific KRAS genotype. The multiplex ddPCR assays had a limit of detection of better than 1 mutant KRAS molecule in 2,000 wild-type KRAS molecules, which compared favourably with a limit of detection of 1 in 50 for next generation sequencing and 1 in 10 for Sanger sequencing. Multiplex ddPCR assays thus provide a highly efficient methodology to identify KRAS mutations in lung adenocarcinoma