3,462 research outputs found

    The Function of E-cadherin in ES Cell Pluripotency

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    Opinion: we need better data about the environmental persistence of plastic goods

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    Author Posting. © National Academy of Sciences, 2020. This article is posted here by permission of National Academy of Sciences for personal use, not for redistribution. The definitive version was published in Proceedings of the National Academy of Sciences of the United States of America 117(26), (2020): 14618-14621, doi:10.1073/pnas.2008009117.Plastic pollution is one of the most visible and complex environmental issues today. Interested and concerned parties include researchers, governmental agencies, nongovernmental organizations, industry, media, and the general public. One key assumption behind the issue and the public outcry is that plastics last indefinitely in the environment, resulting in chronic exposure that harms animals and humans. But the data supporting this assumption are scant.We thank Briana Prado, Cassia Armstrong, and Anna Walsh for their help with the review, Kenneth Kostel, Katie Linehan, Daniel Ward, and Rose Cory for feedback on an earlier version of this piece, John Furfey for assistance with tracking down the original sources of the environmental lifetime estimates, and Natalie Reiner for help with Fig. 1. We acknowledge financial support from Woods Hole Oceanographic Institution (Woods Hole, MA) and the Seaver Institute (Los Angeles, CA).2020-12-1

    Loss of Function of E-Cadherin in Embryonic Stem Cells and the Relevance to Models of Tumorigenesis

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    E-cadherin is the primary cell adhesion molecule within the epithelium, and loss of this protein is associated with a more aggressive tumour phenotype and poorer patient prognosis in many cancers. Loss of E-cadherin is a defining characteristic of epithelial-mesenchymal transition (EMT), a process associated with tumour cell metastasis. We have previously demonstrated an EMT event during embryonic stem (ES) cell differentiation, and that loss of E-cadherin in these cells results in altered growth factor response and changes in cell surface localisation of promigratory molecules. We discuss the implication of loss of E-cadherin in ES cells within the context of cancer stem cells and current models of tumorigenesis. We propose that aberrant E-cadherin expression is a critical contributing factor to neoplasia and the early stages of tumorigenesis in the absence of EMT by altering growth factor response of the cells, resulting in increased proliferation, decreased apoptosis, and acquisition of a stem cell-like phenotype

    A Review of Biomimetic Air Vehicle Research: 1984-2014

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    Biomimetic air vehicles (BAV) are a class of unmanned aircraft that mimic the flapping wing kinematics of flying organisms (e.g. birds, bats, and insects). Research into BAV has rapidly expanded over the last 30 years. In this paper, we present a comprehensive bibliometric review of engineering and biology journal articles that were published on this subject between 1984 and 2014. These articles are organized into five topical categories: aerodynamics, guidance and control, mechanisms, structures and materials, and system design. All of the articles are compartmented into one of these categories based on their primary focus. Several aspects of these articles are examined: publication year, number of citations, journal, authoring organization and country, non-academic funding sources, and the flying organism focused upon for bio-mimicry. This review provides useful information on the state of the art of BAV research and insight on potential future directions. Our intention is that this will serve as a resource for those already engaged in BAV research and enable insight that promotes further research interest

    Crystal structure and substrate specificity of the thermophilic serine:pyruvate aminotransferase from Sulfolobus solfataricus.

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    Journal ArticleResearch Support, Non-U.S. Gov'tThe three-dimensional structure of the Sulfolobus solfataricus serine:pyruvate aminotransferase has been determined to 1.8 Å resolution. The structure of the protein is a homodimer that adopts the type I fold of pyridoxal 5'-phosphate (PLP)-dependent aminotransferases. The structure revealed the PLP cofactor covalently bound in the active site to the active-site lysine in the internal aldimine form. The structure of the S. solfataricus enzyme was also determined with an amino form of the cofactor pyridoxamine 5'-phosphate bound in the active site and in complex with gabaculine, an aminotransferase inhibitor. These structures showed the changes in the enzyme active site during the course of the catalytic reaction. A comparison of the structure of the S. solfataricus enzyme with that of the closely related alanine:glyoxylate aminotransferase has identified structural features that are proposed to be responsible for the differences in substrate specificity between the two enzymes. These results have been complemented by biochemical studies of the substrate specificity and thermostability of the S. solfataricus enzyme.University of ExeterBBSRCEPSRCWellcome Trus

    Benefits of mechatronically guided vehicles on railway track switches

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    Conventional rail vehicles struggle to optimally satisfy the different suspension requirements for various track profiles, such as on a straight track with stochastic irregularities, curved track or switches and crossings (S&C), whereas mechatronically-guided railway vehicles promise a large advantage over conventional vehicles in terms of reduced wheel-rail wear, improved guidance and opening new possibilities in vehicle architecture. Previous research in this area has looked into guidance and steering using MBS models of mechatronic rail vehicles of three different mechanical configurations - secondary yaw control (SYC), actuated solid-axle wheelset (ASW) and driven independently-rotating wheelsets (DIRW). The DIRW vehicle showed the best performance in terms of reduced wear and minimal flange contact and is therefore chosen in this paper for studying the behaviour of mechatronically-guided rail vehicles on conventional S&Cs. In the work presented here, a mechatronic vehicle with the DIRW configuration is run on moderate and high speed track switches. The longer term motivation is to perform the switching function from on-board the vehicle as opposed to from the track as is done conventionally. As a first step towards this, the mechatronic vehicle model is compared against a conventional rail vehicle model on two track scenarios - a moderate speed C type switch and a high speed H switch. A multi-body simulation software is used to produce a high fidelity model of an active rail vehicle with independentlyrotating wheelsets (IRWs) where each wheel has an integrated ’wheelmotor’. This work demonstrates the theory that mechatronic rail vehicles could be used on conventional S&Cs. The results show that the mechatronic vehicle gives a significant reduction in wear, reduced flange contact and improved ride quality on the through-routes of both moderate and high speed switches. On the diverging routes, the controller can be tuned to achieve minimal flange contact and improved ride quality at the expense of higher creep forces and wear

    Novel NDE techniques in the power generation industry

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    The thesis presented here comprises the work undertaken for research into novel NDE techniques in the power generation industry. This has been undertaken as part of the Engineering Doctorate Scheme run by the Research Centre for Non-Destructive Evaluation (RCNDE), which aims to bridge the technological gap between university research and industrial application. In this case, the scheme consisted of two projects completed in conjunction with RWE npower looking at current NDE problems in steam turbine and steam-raising plant. The first project was concerned with detecting microstructural transformation in steam turbine blades, which can act as a precursor to failure by environmentally assisted cracking. This project, and indeed, this entire thesis is principally based on electromagnetic testing methods. An eddy current technique for mapping the microstructural phases was produced and validated as far as was achievable; this offered a significant time-saving advantage over the previous method, by reducing inspection time from 5 man days to just 1.5. The technique has novelty in producing a 2-dimensional map of the blade surface which highlights areas where microstructural phases differ. The second project focuses on the detection of microstructural damage associated with material creep life expiry. This forms a review of the current state of technology and highlights potentially useful paths for future research in both established and emerging NDE technologies, including Magnetic Barkhausen Noise testing and laser-generated ultrasound. Both projects have provided tangible benefit to the sponsoring company and have pushed forward research in a number of technological applications

    Abrogation of E-Cadherin-Mediated Cellular Aggregation Allows Proliferation of Pluripotent Mouse Embryonic Stem Cells in Shake Flask Bioreactors

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    A fundamental requirement for the exploitation of embryonic stem (ES) cells in regenerative medicine is the ability to reproducibly derive sufficient numbers of cells of a consistent quality in a cost-effective manner. However, undifferentiated ES cells are not ideally suited to suspension culture due to the formation of cellular aggregates, ultimately limiting scalability. Significant advances have been made in recent years in the culture of ES cells, including automated adherent culture and suspension microcarrier or embryoid body bioreactor culture. However, each of these methods exhibits specific disadvantages, such as high cost, additional downstream processes or reduced cell doubling times.Here we show that abrogation of the cell surface protein E-cadherin, using either gene knockout (Ecad-/-) or the neutralising antibody DECMA-1 (EcadAb), allows culture of mouse ES cells as a near-single cell suspension in scalable shake flask culture over prolonged periods without additional media supplements. Both Ecad-/- and EcadAb ES cells exhibited adaptation phases in suspension culture, with optimal doubling times of 7.3 h±0.9 and 15.6 h±4.7 respectively and mean-fold increase in viable cell number of 95.1±2.0 and 16±0.9-fold over 48 h. EcadAb ES cells propagated as a dispersed cell suspension for 15 d maintained expression of pluripotent markers, exhibited a normal karyotype and high viability. Subsequent differentiation of EcadAb ES cells resulted in expression of transcripts and proteins associated with the three primary germ layers.This is the first demonstration of the culture of pluripotent ES cells as a near-single cell suspension in a manual fed-batch shake flask bioreactor and represents a significant improvement on current ES cell culture techniques. Whilst this proof-of-principle method would be useful for the culture of human ES and iPS cells, further steps are necessary to increase cell viability of hES cells in suspension
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