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Fracture mechanics by three-dimensional crack-tip synchrotron X-ray microscopy
No full textP. J. Withers1,2⇑1Manchester X-ray Imaging Facility, School of Materials, Manchester University, Manchester M13 9PL, UK2Research Complex at Harwell, Rutherford Appleton Laboratory, Harwell Oxford, Didcot OX11 0FA, UKe-mail: p.j.withers{at}manchester.ac.ukAbstract To better understand the relationship between the nucleation and growth of defects and the local stresses and phase changes that cause them, we need both imaging and stress mapping. Here, we explore how this can be achieved by bringing together synchrotron X-ray diffraction and tomographic imaging. Conventionally, these are undertaken on separate synchrotron beamlines; however, instruments capable of both imaging and diffraction are beginning to emerge, such as ID15 at the European Synchrotron Radiation Facility and JEEP at the Diamond Light Source. This review explores the concept of three-dimensional crack-tip X-ray microscopy, bringing them together to probe the crack-tip behaviour under realistic environmental and loading conditions and to extract quantitative fracture mechanics information about the local crack-tip environment. X-ray diffraction provides information about the crack-tip stress field, phase transformations, plastic zone and crack-face tractions and forces. Time-lapse CT, besides providing information about the three-dimensional nature of the crack and its local growth rate, can also provide information as to the activation of extrinsic toughening mechanisms such as crack deflection, crack-tip zone shielding, crack bridging and crack closure. It is shown how crack-tip microscopy allows a quantitative measure of the crack-tip driving force via the stress intensity factor or the crack-tip opening displacement. Finally, further opportunities for synchrotron X-ray microscopy are explored. computer tomographyX-ray microscopyfracture mechanics (LEFM)synchrotron X-raysFootnotesOne contribution of 15 to a theme issue ‘Research achieved with Diamond and future perspectives’.© 2015 The Authors. Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited
Impact of age on access site-related outcomes in 469,983 percutaneous coronary intervention procedures: Insights from the British Cardiovascular Intervention Society
No full textWe investigate adoption of the TRA in different age groups and study the relationship between age and access site related outcomes in a national cohort of patients undergoing PCI in the UK. Previous studies have reported conflicting data on radial access site adoption between different age groups, with age an independent predictor of failure of procedures undertaken through the radial approach. Age and access site related outcomes (based on transradial (TRA) and transfemoral (TFA) access) were studied in 469,983 PCI procedures undertaken in the UK from 2006 to 2012 in the age groups
Lamellipodin Is Important for Cell-to-Cell Spread and Actin-Based Motility in Listeria monocytogenes
No full textListeria monocytogenes is a foodborne pathogen capable of invading a broad range of cell types and replicating within the host cell cytoplasm. This paper describes the colocalization of host cell lamellipodin (Lpd) with intracellular L. monocytogenes detectable 6 h postinfection of epithelial cells. The association was mediated via interactions between both the peckstrin homology (PH) domain in Lpd and phosphatidylinositol (3,4)-bisphosphate [PI(3,4)P2] on the bacterial surface and by interactions between the C-terminal EVH1 (Ena/VASP [vasodilator-stimulated phosphoprotein] homology domain 1) binding domains of Lpd and the host VASP (vasodilator-stimulated phosphoprotein) recruited to the bacterial cell surface by the listerial ActA protein. Depletion of Lpd by short interfering RNA (siRNA) resulted in reduced plaque size and number, indicating a role for Lpd in cell-to-cell spread. In contrast, overexpression of Lpd resulted in an increase in the number of L. monocytogenes-containing protrusions (listeriopods). Manipulation of the levels of Lpd within the cell also affected the intracellular velocity of L. monocytogenes, with a reduction in Lpd corresponding to an increase in intracellular velocity. These data, together with the observation that Lpd accumulated at the interface between the bacteria and the developing actin tail at the initiation of actin-based movement, indicate a possible role for Lpd in the actin-based movement and the cell-to-cell spread of L. monocytogenes
Handbook of Vascular Biology Techniques
No full textChapter 26: Preparation of Liposomes with Dual Fluorophores to Follow Real-Time Content Release In Vivo.AbstractUnilamellar liposomes are well established carriers of chemotherapeutics. Most of the clinically approved liposome formulations for cancer treatment tend to rely on passive targeting of the tumour site, enabled by the leaky vasculature supplying the tumour tissue. This chapter deals with a method of preparing liposomes having two different fluorophores encapsulated in separate compartments; the lipid bilayer buries the non-exchangeable fluorophore while the aqueous interior (lumen) encapsulates the releasable payload. Such preparations can be used to quantitatively assess the ability of a particular formulation to release payload by deciphering the effects of accumulation and plasma clearance from actual content release within the microvasculature in live tissues and in real-time. The emphasis here is on liposome preparation by the technique of extrusion through polycarbonate membranes
High-accuracy heterodyne detection of THz radiation exploiting telecommunication technologies
No full textWe report the first open-loop heterodyne technique using standard telecom optical fiber components for spectral characterization of THz semiconductor lasers. This allows the measurement of continuous modal tuning with sub-GHz accuracy and 20dB dynamic range
Consensus communication on early peanut introduction and the prevention of peanut allergy in high-risk infants.
No full textThe purpose of this brief communication is to highlight emerging evidence to existing guidelines regarding potential benefits of supporting early, rather than delayed, peanut introduction during the period of complementary food introduction in infants. This document should be considered as interim guidance based on consensus among the following organizations: American Academy of Allergy, Asthma & Immunology, American Academy of Pediatrics, American College of Allergy, Asthma & Immunology, Australasian Society of Clinical Immunology and Allergy, Canadian Society of Allergy and Clinical Immunology, European Academy of Allergy and Clinical Immunology, Israel Association of Allergy and Clinical Immunology, Japanese Society for Allergology, Society for Pediatric Dermatology, and World Allergy Organization. More formal guidelines regarding early-life, complementary feeding practices and the risk of allergy development will follow in the next year from the National Institute of Allergy and Infectious Diseases-sponsored Working Group and the European Academy of Allergy and Clinical Immunology
Integrative analysis of kinase networks in TRAIL-induced apoptosis provides a source of potential targets for combination therapy.
No full textTumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is an endogenous secreted peptide and, in preclinical studies, preferentially induces apoptosis in tumor cells rather than in normal cells. The acquisition of resistance in cells exposed to TRAIL or its mimics limits their clinical efficacy. Because kinases are intimately involved in the regulation of apoptosis, we systematically characterized kinases involved in TRAIL signaling. Using RNA interference (RNAi) loss-of-function and cDNA overexpression screens, we identified 169 protein kinases that influenced the dynamics of TRAIL-induced apoptosis in the colon adenocarcinoma cell line DLD-1. We classified the kinases as sensitizers or resistors or modulators, depending on the effect that knockdown and overexpression had on TRAIL-induced apoptosis. Two of these kinases that were classified as resistors were PX domain-containing serine/threonine kinase (PXK) and AP2-associated kinase 1 (AAK1), which promote receptor endocytosis and may enable cells to resist TRAIL-induced apoptosis by enhancing endocytosis of the TRAIL receptors. We assembled protein interaction maps using mass spectrometry-based protein interaction analysis and quantitative phosphoproteomics. With these protein interaction maps, we modeled information flow through the networks and identified apoptosis-modifying kinases that are highly connected to regulated substrates downstream of TRAIL. The results of this analysis provide a resource of potential targets for the development of TRAIL combination therapies to selectively kill cancer cells
Developing eco-innovations: a three-stage typology of supply networks
No full textThis paper uses grounded theory to develop and deepen our understanding of eco-innovation. It pre- sents, through a series of four propositions, a three-stage supply network typology to help scholars and managers consider how best to develop these innovations. This typology was constructed by reviewing existing sustainability frameworks that argued that innovation was a key factor in sustainability. Moreover we found little consideration given on how to discover and develop eco-innovations. The literature proposes that a firm with strong ties with a few strategic suppliers will benefit from the knowledge and technology that spills over from suppliers to the firm during the new product devel- opment process. In contrast, the network literature explains that the creation of multiple weak ties to non-strategic suppliers may increase opportunities for identifying innovation. The network literature further suggests a third and potentially more promising route: building weak ties to suppliers that bridge ‘structural holes’ in the network. We suggest that strong ties with strategic suppliers will lead to the development of incremental eco-innovations while weak ties with multiple suppliers and with suppliers that bridge structural holes will tend to lead to radical eco-innovations. Finally, we suggest that once eco- innovations are developed they should be embedded in the operational processes of other suppliers to increase the sustainability performance of the focal firm
On the computation of the Hashin-Shtrikman bounds for transversely isotropic two-phase linear elastic fibre-reinforced composites
No full textComplexity in the law and administration of social security: is it really a problem?
No full textThis article analyses the problem of complexity in relation to the law and structure of the modern welfare (social security) system and its impact on administration, which has represented a significant driver for simplification reforms in the UK. The article outlines diverse conceptual and methodological approaches to the definition of complexity. It argues that despite the difficulties which complexity presents, attention should also be paid to the dangers of simplification and that a degree of complexity in relation to social security provision may be necessary if rights to welfare are to be adequately safeguarded