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Harwell, United Kingdom

Al-Ahmady Z.S.,University of Manchester | Al-Ahmady Z.S.,University College London | Scudamore C.L.,Harwell Science and Innovation Campus | Kostarelos K.,University of Manchester | Kostarelos K.,University College London
International Journal of Cancer | Year: 2015

Temperature-sensitive vesicles designed by inclusion of leucine zipper peptides within a lipid bilayer (Lp-Peptide hybrids) encapsulating Doxorubicin (DOX) have been reported. Intravenous administration of these constructs prolonged blood circulation kinetics and increased tumor accumulation in vivo with local mild hyperthermia. In this study, the biological activity of the DOX-loaded Lp-Peptide hybrid vesicles was further investigated at the cellular level and in vivo compared to lysolipid-containing temperature-sensitive liposomes (LTSL) and traditional temperature-sensitive liposomes. Lp-Peptide vesicles were not toxic to cell cultures at 37°C, while effective cancer cell toxicity was observed after 1 hr of heating at 42°C. The activity of Lp-Peptide vesicles in vivo was studied using two different heating protocols to obtain tumor intravascular or interstitial drug release. Lp-Peptide vesicle treatment allowing intravascular DOX release showed equally effective tumor growth retardation and survival to that of LTSL treatment. The Lp-Peptide vesicles also offered therapeutic responses using the alternative heating protocol to maximise drug release within the tumor interstitium. Matching the drug release kinetics of temperature-sensitive vesicles with the heating protocol applied is considered the most critical factor to determine therapeutic efficacy in the clinical translation of such modalities. © 2015 UICC. Source


Rajeevan N.E.,University of Calicut | Kumar R.,National Institute of Technology Hamirpur | Shukla D.K.,German Electron Synchrotron | Thakur P.,Harwell Science and Innovation Campus | Pradyumnan P.P.,University of Calicut
Key Engineering Materials | Year: 2013

The effect of swift heavy ion (SHI) irradiation on the structural and magnetic properties of thin films of Bi-substituted Co2MnO 4 prepared by Pulsed Laser Deposition (PLD) is presented. XRD analysis reveals that the BixCo2-x MnO4 (x = 0.0, 0.1 & 0.3) films grown on amorphous quartz, and crystalline LaAlO3 (LAO) exhibited single phase cubic spinel structure with low strain before and after the irradiation at 200 MeV Ag15+ ions at three fluence values 1 × 1011, 5 × 1011 and 1 × 1012 ions/cm2. DC magnetization hysteresis loop study of the films revealed a ferrimagnetic ordering below the transition temperature ∼ 185 K and the saturation magnetization was increased by the irradiation at optimal fluence value 5×1011 ions/cm2. X-ray Magnetic Circular Dichroism (XMCD) studies showed the antiparallel alignments of Co and Mn magnetic moments. Copyright © 2013 Trans Tech Publications Ltd. Source


As the low hanging lightweighting fruits are picked, automotive manufacturers have to now work that bit harder to shed the pounds. BMW is perhaps one of the more progressive examples of a manufacturer driving composite R&D in a major way. However, it is not simply abandoning metal, and like many others, it is seeking out ways to lightweight vehicles using conventional steel. This has led to BMW Mini initiating a project between The University of Oxford and Diamond Light Source – the UK's national synchrotron science facility located at the Harwell Science and Innovation Campus in Oxfordshire. The facility harnesses the power of electrons and x-rays to help scientists and engineers gain new insight and understanding in to the microscopic and internal structures of materials. BMW Mini wants answers to a phenomenon that has been witnessed, more broadly, since the 1950s. It is seen when parts are stamp formed, a common automotive process, to make everything from bonnets to doors. The problem is, for any stamping process that is completed in more than one stage, the deformation becomes highly complex, particularly for a pressed part with strain applied in two-axes. This results in a non-homogeneous arrangement of the crystalline and microscopic defect structures. While it may sound arbitrary, the affect can influence grain morphology, crystal orientation and distribution – all of which have significant impact on mechanical properties, including most importantly, how much the material will stretch before it fractures. Leading the work is Dr David Collins, a researcher at the University of Oxford, who explains the problem. He says: "They can't stamp form stronger steels at the moment because of this affect. The metals they use on body panels are actually quite weak, say 10% as strong as the strongest steels on the market. Stronger metals are not ductile and can't be stamped into the complicated shapes needed." It means thicker sections have to be used, so panels end up weighing more. It's something BMW is keen to understand so it can ultimately reduce the weight of steel chassis. The problem is complex, meaning testing and analysis is far from straightforward. The deformation is biaxial, meaning any obvious traditional solution is not suitable. It led to Dr Collins applying to use the synchrotron to carry out tests and shed new light, or x-rays in this case, on the problem. However, he soon faced another problem, the Shimadzu AGS-X 10kN load frame that was available, was a single axis machine. Dr Collins decided to do what so many engineers have done before him – innovate. He designed a mechanism to generate the bi-axial deformation needed, which also bolts straight on to the Shimadzu machine. "I've built a mechanism that uses the power of the load frame to generate the stresses," he says. "There are four diagonal rods at the corners to change the angle and determine the ratio of how much it is deforming in each direction. I can make it more biased towards the horizontal, vertical or even one side. "I spent time in the workshop machining all the components myself. I started from scratch and it was a very steep learning curve. I broke a lot of tools and upset a couple of people, but I was very determined to make the mechanism and run the tests." The request to use the synchrotron was successful and four days of testing commenced. The results show a series of concentric rings, with each ring corresponding to a signal coming from individual lattice planes. The shape of these rings, and their radius, gives an important microscopic insight. "If you deform a bit of material, those rings change in diameter," he says. "And you can then measure how much strain is being taken up by individual planes. So you capture what is happening on the atomic planar level." The cross shaped specimen is 1mm thick, but in the centre this is reduced to just 300µm. If it was a uniform thickness, the test would simply pull the arms off. A cross is machined in the middle, which steps down to a thinner circular cross section just 300µm thick. "One thing you can see is how strain is being accommodated in the individual grains based on their orientations," says Dr Collins. "You can monitor the centre on a macroscopic level by putting a camera in front of the rig. But with x-rays, they tell you what the strain is, on all of the individual crystals." With the tests complete, the hard work begins. After four intense days of gathering data, it could be a year or more of analysis to find conclusive explanation of the bi-axial deformation phenomenon. What is known is that 'material texture', ie the orientation of grains in the material, has a big effect on the ductility of the materials and how strain is accumulated. As all sheet materials are rolled during production, it forces most of the crystals to align in one orientation. "We can tell BMW things like 'texture is important', but we don't yet know how to optimise it," says Dr Collins. "Eventually, however, we hope to get enough of an idea about the affect to apply it to different materials. We're sticking with steel for the moment as we don't want to end up blurring the problem with other complexities. But, there is no reason why this research could not be limited to any alloy. For a lot of metals, no one has proved if this phenomenon even exists or not, so there might be massive benefits with lots of different applications outside the automotive world." Explore further: A new twist makes for better steel


Alianelli L.,Diamond Light Source | Sawhney K.J.S.,Diamond Light Source | Barrett R.,European Synchrotron Radiation Facility | Pape I.,Diamond Light Source | And 2 more authors.
Optics Express | Year: 2011

Modern synchrotron sources have provided for decades intense beams of photons over a large energy spectrum. The availability of improved optics and detectors has opened up new opportunities for the study of matter at the micrometre and nanometre scale in many disciplines. Whilst exploitation of micro-focused beams occurs almost daily in many beamlines, the production of beams of 100 nm is achieved on few instruments which use specialised optics. Refractive lenses, zone plates, curved mirrors, multilayers, and multilayer Laue lenses, can all focus x-rays to less than 50 nm under strict beam stability conditions. Focusing the synchrotron radiation to beam sizes smaller than 10 nm is considered the ultimate goal for the current decade. Silicon micro-technology has so far provided some of the most advanced x-ray refractive lenses; we report on design and characterisation of a novel silicon kinoform lens that is capable of delivering nano-beams with high efficiency. ©2011 Optical Society of America. Source


Osborn D.P.S.,St Georges, University of London | Roccasecca R.M.,Wellcome Trust Sanger Institute | McMurray F.,Harwell Science and Innovation Campus | Hernandez-Hernandez V.,University College London | And 7 more authors.
PLoS ONE | Year: 2014

Common intronic variants in the Human fat mass and obesity-associated gene (FTO) are found to be associated with an increased risk of obesity. Overexpression of FTO correlates with increased food intake and obesity, whilst loss-of-function results in lethality and severe developmental defects. Despite intense scientific discussions around the role of FTO in energy metabolism, the function of FTO during development remains undefined. Here, we show that loss of Fto leads to developmental defects such as growth retardation, craniofacial dysmorphism and aberrant neural crest cells migration in Zebrafish. We find that the important developmental pathway, Wnt, is compromised in the absence of FTO, both in vivo (zebrafish) and in vitro (Fto-/- MEFs and HEK293T). Canonical Wnt signalling is down regulated by abrogated β-Catenin translocation to the nucleus whilst non-canonical Wnt/Ca2+ pathway is activated via its key signal mediators CaMKII and PKCδ. Moreover, we demonstrate that loss of Fto results in short, absent or disorganised cilia leading to situs inversus, renal cystogenesis, neural crest cell defects and microcephaly in Zebrafish. Congruently, Fto knockout mice display aberrant tissue specific cilia. These data identify FTO as a protein-regulator of the balanced activation between canonical and non-canonical branches of the Wnt pathway. Furthermore, we present the first evidence that FTO plays a role in development and cilia formation/function. © 2014 Osborn et al. Source

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