α5β1-Integrin promotes tension-dependent mammary epithelial cell invasion by engaging the fibronectin synergy site.

Tumors are fibrotic and characterized by abundant, remodeled, and cross-linked collagen that stiffens the extracellular matrix stroma. The stiffened collagenous stroma fosters malignant transformation of the tissue by increasing tumor cell tension to promote focal adhesion formation and potentiate growth factor receptor signaling through kinase. Importantly, collagen cross-linking requires fibronectin (FN). Fibrotic tumors contain abundant FN, and tumor cells frequently up-regulate the FN receptor α5β1 integrin. Using transgenic and xenograft models and tunable two- and three-dimensional substrates, we show that FN-bound α5β1 integrin promotes tension-dependent malignant transformation through engagement of the synergy site that enhances integrin adhesion force. We determined that ligation of the synergy site of FN permits tumor cells to engage a zyxin-stabilized, vinculin-linked scaffold that facilitates nucleation of phosphatidylinositol (3,4,5)-triphosphate at the plasma membrane to enhance phosphoinositide 3-kinase (PI3K)-dependent tumor cell invasion. The data explain why rigid collagen fibrils potentiate PI3K activation to promote malignancy and offer a perspective regarding the consistent up-regulation of α5β1 integrin and FN in many tumors and their correlation with cancer aggression

External review of the storage plan for the Peterhead Carbon Capture and Storage Project

This document summarises the findings of an external independent review of the storage plan for the proposed Peterhead Carbon Capture and Storage project which aims to store up to 20 million tonnes (Mt) of CO2 within the framework of the European Directive on the geological storage of CO2. The Peterhead Carbon Capture and Storage Project proposes to capture carbon dioxide (CO2) from an existing gas-fired power-station at Peterhead and to store this in geological strata at a depth of around 2600 m beneath the outer Moray Firth. The plan is to store 10 - 15 Mt of CO2 over a ten to fifteen-year period commencing around 2020, but the site is being qualified for 20 Mt to allow for potential extension of the injection period. Storage will utilise the depleted Goldeneye gas condensate field with the Captain Sandstone reservoir as the primary storage container. The Storage Site covers some 70 km2, and comprises the Captain Sandstone and underlying strata of the Cromer Knoll Group, bounded by a polygon some 2 to 3 km outside of the original Goldeneye oil-water contact. The Storage Complex is larger, around 154 km2, bounded some 2 to 7 km outside of the original oil-water contact, and extending upwards to the top of the Dornoch Mudstone at a depth of more than 800 m. The top-seal of the primary container is a proven caprock for natural gas and is formed by the mudstones of the Upper Cromer Knoll Group, the overlying Rødby and Hidra formations and the Plenus Marl. A number of additional seals are present in the overburden within the Storage Complex, as are a number of potential secondary containers which could also serve as monitoring horizons. The geological interpretation of the storage site is based on the comprehensive datasets acquired during the discovery, appraisal and development of the Goldeneye field, and also data from other wells, fields and seismic surveys in the surrounding area. The static geological model of the storage site and adjacent aquifer has been stress tested for the key uncertainties, and it is considered to be robust. The storage capacity of the Goldeneye structure has been calculated using both static (volumetric) methods and dynamic flow modelling together with uncertainty analysis. Total estimated capacity of the structural closure is in the range 25 to 47 Mt and so robustly exceeds the proposed injected amount

Preparation, structural characterisation and antibacterial properties of Ga-doped sol-gel phosphate-based glass

A sol-gel preparation of Ga-doped phosphate-based glass with potential application in antimicrobial devices has been developed. Samples of composition (CaO)(0.30)(Na2O)(0.20-x) (Ga2O3) (x) (P2O5)(0.50) where x = 0 and 0.03 were prepared, and the structure and properties of the gallium-doped sample compared with those of the sample containing no gallium. Analysis of the P-31 MAS NMR data demonstrated that addition of gallium to the sol-gel reaction increases the connectivity of the phosphate network at the expense of hydroxyl groups. This premise is supported by the results of the elemental analysis, which showed that the gallium-free sample contains significantly more hydrogen and by FTIR spectroscopy, which revealed a higher concentration of -OH groups in that sample. Ga K-edge extended X-ray absorption fine structure and X-ray absorption near-edge structure data revealed that the gallium ions are coordinated by six oxygen atoms. In agreement with the X-ray absorption data, the high-energy XRD results also suggest that the Ga3+ ions are octahedrally coordinated with respect to oxygen. Antimicrobial studies demonstrated that the sample containing Ga3+ ions had significant activity against Staphylococcus aureus compared to the control

Search for Insect Neuroactive Substances Using an Electrophysiolofical Method

A simple and rapid bioassay was developed to search for novel insect neuroactive substances.This method was based on the electrophysiological response of the metathoracic legnerve of Periplaneta americana.Using this assay,41 methanol extracts of Kenyan plant and 15 methanol extracts of Indonesia plants were tested to show various activities.Several compounds were isolated from these methanol extracts with the guidance of the activity increasing spontaneous-impulse frequencies.地球規模での環境問題に関心が高まりつつある現在、病害虫防除のための薬剤に求められているのは、ターゲットに対する強力な効果はもちろんのこと、高い選択性と適度な生分解性である。そのような優れた特性をもつ薬剤のリード化合物となる生理活性物質を自然界から見出そうと、これまでに数多くの試みがなされてきた。その手段となるのが生物試験であり、新たな生物試験の開発が新規の活性化合物の発見につながることもある。そこで著者は、昆虫の神経を作用点とする天然生理活性物質を探索するための新たな生物試験法の開発を試みた。昆虫神経作用物質は、その効果が強力かつ速効性であることが多い点、また、植物や微生物に対し影響を及ぼしにくい点で有効なリード化合物として期待される。さらに、昆虫と哺乳動物とでは代謝に多くの違いがあるため、昆虫には強力な毒性を示しても人畜への毒性は低いことが多い。天然ピレスロイドは、このような昆虫神経作用物質の長所を合わせ持つ、理想的な例であった。自然界には、ピレスロイドと同等、またはそれ以上に優れた防除剤となりうる昆虫神経作用物質が存在するはずである。しかし、昆虫神経作用物質探索のための生物試験法はまだ一般的ではない。神経活動の観察には通常、電気生理学的手法が用いられているが、細かい作業と長い時間を要すものが多く、薬剤の作用機構の解明など、生理学的研究の手段とはなっても、スクリーニングのための生物試験として確立されたものはほどんど知られていない。著者はワモンゴキブリ（Periplanata americana)の後肢神経系を用いて、昆虫神経作用物質探索のための簡便で迅速な生物試験法を開発した。また、この試験を指標としてケニヤ産植物およびインドネシア産植物のメタノール抽出物から、いくつかの活性化合物を単離した

Span of control in supervision of rail track work

The supervision of engineering work on the railways has received relatively little examination despite being both safety-critical in its own right and having wider implications for the successful running of the railways. The present paper is concerned with understanding the factors that make different engineering works perceived as easier or harder to manage. We describe an approach building on notions of ‘span of control’, through which we developed the TOECAP inventory (Team, Organisation, Environment, Communication, Activity and Personal). This tool was validated through both interviews and questionnaires. As well as identifying the physical factors involved, the work also emphasised the importance of collaborative and attitudinal factors. We conclude by discussing limitations of the present work and future directions for development

Risk assessment for the spread of Serratia marcescens within dental-unit waterline systems using Vermamoeba vermiformis

Vermamoeba vermiformis is associated with the biofilm ecology of dental-unit waterlines (DUWLs). This study investigated whether V. vermiformis is able to act as a vector for potentially pathogenic bacteria and so aid their dispersal within DUWL systems. Clinical dental water was initially examined for Legionella species by inoculating it onto Legionella selective-medium plates. The molecular identity/profile of the glassy colonies obtained indicated none of these isolates were Legionella species. During this work bacterial colonies were identified as a non-pigmented Serratia marcescens. As the water was from a clinical DUWL which had been treated with Alpron™ this prompted the question as to whether S. marcescens had developed resistance to the biocide. Exposure to Alpron™ indicated that this dental biocide was effective, under laboratory conditions, against S. marcescens at up to 1x108 colony forming units/millilitre (cfu/ml). V. vermiformis was cultured for eight weeks on cells of S. marcescens and Escherichia coli. Subsequent electron microscopy showed that V. vermiformis grew equally well on S. marcescens and E. coli (p = 0.0001). Failure to detect the presence of S. marcescens within the encysted amoebae suggests that V. vermiformis is unlikely to act as a vector supporting the growth of this newly isolated, nosocomial bacterium

On the Production of π+π+\pi^+\pi^+ Pairs in pp Collisions at 0.8 GeV

Data accumulated recently for the exclusive measurement of the $pp\to pp\pi^+\pi^-$ reaction at a beam energy of 0.793 GeV using the COSY-TOF spectrometer have been analyzed with respect to possible events from the $pp \to nn\pi^+\pi^+$ reaction channel. The latter is expected to be the only $\pi\pi$ production channel, which contains no major contributions from resonance excitation close to threshold and hence should be a good testing ground for chiral dynamics in the $\pi\pi$ production process. No single event has been found, which meets all conditions for being a candidate for the $pp \to nn \pi^+\pi^+$ reaction. This gives an upper limit for the cross section of 0.16 $\mu$b (90% C.L.), which is more than an order of magnitude smaller than the cross sections of the other two-pion production channels at the same incident energy

The role of childhood social position in adult type 2 diabetes: Evidence from the English Longitudinal Study of Ageing

Copyright @ 2014 Pikhartova et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.This article has been made available through the Brunel Open Access Publishing Fund.Background: Socioeconomic circumstances in childhood and early adulthood may influence the later onset of chronic disease, although such research is limited for type 2 diabetes and its risk factors at the different stages of life. The main aim of the present study is to examine the role of childhood social position and later inflammatory markers and health behaviours in developing type 2 diabetes at older ages using a pathway analytic approach. Methods. Data on childhood and adult life circumstances of 2,994 men and 4,021 women from English Longitudinal Study of Ageing (ELSA) were used to evaluate their association with diabetes at age 50 years and more. The cases of diabetes were based on having increased blood levels of glycated haemoglobin and/or self-reported medication for diabetes and/or being diagnosed with type 2 diabetes. Father's job when ELSA participants were aged 14 years was used as the measure of childhood social position. Current social characteristics, health behaviours and inflammatory biomarkers were used as potential mediators in the statistical analysis to assess direct and indirect effects of childhood circumstances on diabetes in later life. Results: 12.6 per cent of participants were classified as having diabetes. A disadvantaged social position in childhood, as measured by father's manual occupation, was associated at conventional levels of statistical significance with an increased risk of type 2 diabetes in adulthood, both directly and indirectly through inflammation, adulthood social position and a risk score constructed from adult health behaviours including tobacco smoking and limited physical activity. The direct effect of childhood social position was reduced by mediation analysis (standardised coefficient decreased from 0.089 to 0.043) but remained statistically significant (p = 0.035). All three indirect pathways made a statistically significantly contribution to the overall effect of childhood social position on adulthood type 2 diabetes. Conclusions: Childhood social position influences adult diabetes directly and indirectly through inflammatory markers, adulthood social position and adult health behaviours. © 2014Pikhartova et al.; licensee BioMed Central Ltd.Economic and Social Research Council-funded International Centre for Life Course Studies in Society and Health (RES-596-28-0001)

The pp -> pp pi pi pi reaction channels in the threshold region

The cross section for prompt neutral and charged three pion production in pp interactions was measured at excess energies in the range 160 - 217 MeV. That comprises the first measurement of the pp->pp pi0pi0pi0 reaction and the comparison with the pp->pp pi+pi-pi0 reaction, in a very direct way. The experiment was performed above the eta meson production threshold and the cross section normalization was obtained from a concurrent measurement of the reaction pp->pp eta with the eta decaying into 3 pions. Since the same final states are selected, the measurement has a low systematical error. The measured cross section ratio sigma(pp->pp pi+pi-pi0)/sigma(pp->pp pi0\pi0\pi0) is compared to predictions of dominance of different isobars in the intermediate state.Comment: 12 pages, 4 figures New discussion on the pp->pp3pi reaction mechanis