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Janeczek A.A.,University of Southampton | Scarpa E.,University of Southampton | Horrocks M.H.,University of Cambridge | Tare R.S.,University of Southampton | And 6 more authors.
Nanomedicine | Year: 2017

Aim: To fabricate PEGylated liposomes which preserve the activity of hydrophobic Wnt3A protein, and to demonstrate their efficacy in promoting expansion of osteoprogenitors from human bone marrow. Methods: PEGylated liposomes composed of several synthetic lipids were tested for their ability to preserve Wnt3A activity in reporter and differentiation assays. Single-molecule microspectroscopy was used to test for direct association of protein with liposomes. Results: Labeled Wnt3A protein directly associated with all tested liposome preparations. However, Wnt3A activity was preserved or enhanced in PEGylated 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) liposomes but not in PEGylated 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) liposomes. PEGylated Wnt3A liposomes associated with skeletal stem cell populations in human bone marrow and promoted osteogenesis. Conclusion: Active Wnt protein-containing PEGylated liposomes may have utility for systemic administration for bone repair. © 2017 Nicholas Evans.


Rice H.,Porton Group | Mann T.M.,Porton Group | Armstrong S.J.,Porton Group | Price M.E.,Porton Group | And 2 more authors.
Chemico-Biological Interactions | Year: 2016

The provision of effective Medical Countermeasures (MedCM) for all agents and routes of exposure is a strategic goal of defence research and development. In the case of military autoinjector-based therapies for nerve agent poisoning, current treatment effectiveness is limited by the oxime reactivator being effective against only certain agents, by rapid clearance times of the drugs and because the doses may not be optimal for treatment of severe poisoning. Prolonged poisoning by nerve agents entering the body through the skin is also challenging. Since casualty handling timelines have reduced significantly in recent years, it may be sufficient for first aid therapy to provide protection for only a few hours until further medical treatment is available. Therefore, the traditional evaluation of first aid therapy in animal models of survival at 24 h may not be appropriate. At various echelons of medical care, further therapeutic interventions are possible. The current basis for the medical management of nerve-agent poisoned casualties is derived mainly from clinical experience with pesticide poisoning. Adjunct therapy with a bioscavenger (such as human butyrylcholinesterase (huBChE)), could have utility as a delayed intervention by reducing the toxic load. It has previously been demonstrated that huBChE is an effective post-exposure therapy against percutaneous VX poisoning. It is recommended that the scope of animal models of nerve agent MedCM are extended to cover evaluation of both first aid MedCM over significantly reduced timescales, and subsequent supportive therapeutic and medical management strategies over longer timescales. In addition to bioscavengers, these strategies could include repeated combined and individual therapy drugs to alleviate symptoms, other classes of drugs or ventilatory support. Crown Copyright © [2016] Published by Elsevier Ireland Ltd. This is an open access article under the Open Government Licence (OGL) (http://www.nationalarchives.gov.uk/doc/open-government-licence/version/3/). © 2016


Hansford K.M.,Porton Group | Fonville M.,National Institute for Public Health and the Environment RIVM | Jahfari S.,National Institute for Public Health and the Environment RIVM | Sprong H.,National Institute for Public Health and the Environment RIVM | Medlock J.M.,Porton Group
Epidemiology and Infection | Year: 2015

This paper reports the first detection of Borrelia miyamotoi in UK Ixodes ricinus ticks. It also reports on the presence and infection rates of I. ricinus for a number of other tick-borne pathogens of public health importance. Ticks from seven regions in southern England were screened for B. miyamotoi, Borrelia burgdorferi sensu lato (s.l.), Anaplasma phagocytophilum and Neoehrlichia mikurensis using qPCR. A total of 954 I. ricinus ticks were tested, 40 were positive for B. burgdorferi s.l., 22 positive for A. phagocytophilum and three positive for B. miyamotoi, with no N. mikurensis detected. The three positive B. miyamotoi ticks came from three geographically distinct areas, suggesting a widespread distribution, and from two separate years, suggesting some degree of endemicity. Understanding the prevalence of Borrelia and other tick-borne pathogens in ticks is crucial for locating high-risk areas of disease transmission. © 2014 Cambridge University Press.


Clarke S.D.,University of Sheffield | Fay S.D.,University of Sheffield | Fay S.D.,Blastech Ltd | Warren J.A.,University of Sheffield | And 7 more authors.
International Journal of Impact Engineering | Year: 2015

The role of the geotechnical conditions on the impulse delivered by a shallow buried charge has received much attention in recent times. As the importance of the soil in these events has become better understood, the control over the geotechnical conditions has improved. While previous work has investigated directly the role of geotechnical conditions on the magnitude of the impulse from a buried charge, the current work aims to identify how these same conditions also affect the repeatability of testing using soils. In this paper the authors draw together their work to date for a wide range of different soil types and moisture contents to investigate the variation in output from nominally identical tests. The methodology for the preparation of soil beds and the measurement of impulse is described along with the measured variations in peak and residual deflections of a target plate fixed to the impulse measurement apparatus. © 2015 Elsevier Ltd.


Baber C.,University of Birmingham | Attfield S.,Middlesex University | Conway G.,Porton Group | Rooney C.,Middlesex University | Kodagoda N.,Middlesex University
International Journal of Human Computer Studies | Year: 2016

Sense-making plays an important role in Intelligence Analysis, but can be difficult to study in situ. Thus, it is useful to exploit training exercises to study this phenomenon. In this paper two versions of the same exercise are reported: one undertaken by participants at a conference and one undertaken by Military Intelligence personnel. The behaviour of groups of analysts (experienced versus inexperienced) is considered in terms the Data/Frame model of sense-making. The paper illustrates how Intelligence Analysis often involves parallel and overlapping explorations of data, with multiple frames that might be minimal and sketchy. The use of representations, such as link diagrams, provides a means of externalising frames and it is suggested that these can shift the style of reasoning exhibited by the teams as the Exercise progresses. Such a shift was seen more clearly in the behaviour of the Military Intelligence Officers who also spent more time developing and refining the diagrams to support the presentation of their findings. © 2015 Elsevier Ltd. All rights reserved.


Titterton D.H.,UK Defence Science and Technology Laboratory | Carpenter S.R.,Porton Group
Imaging Science Journal | Year: 2010

Optical techniques have been developed to provide a relatively simple but effective homing heads for guided weapons over the last five decades. The original approaches tended to use single detectors operating around "two microns" in the infrared. Improvements in detector technology have enabled significant enhancements to the performance of such seekers. Development of focal-plane array technology provided an opportunity to design and develop imaging seeker technology. This type of seeker technology appears to be resilient to conventional optical countermeasure techniques. This paper describes the development of an imaging infrared seeker to investigate potential infrared countermeasure techniques to defeat mechanisms. © 2010 Maney Publishing.


Pinto R.,Cranfield University | Carr D.,Cranfield University | Helliker M.,Porton Group | Girvan L.,University of Otago | Gridley N.,NP Aerospace
Textile Research Journal | Year: 2012

Personal armor, including body armor, is protective clothing designed to either absorb or deflect attacks that would usually be fatal to an individual. These attacks include, but are not limited to, slashing, bludgeoning, stabbing and ballistic threats. In the UK, body armor is worn by police officers for their shift; however, military personnel (particularly when based overseas) may wear body armor continuously for much longer time periods. Thus, the effect of wear due to use on the performance of body armor is of interest. Testing of body armor after actual use is problematic for several reasons including, but not limited to, (i) access to such items and (ii) a lack of knowledge of exactly what the body armor has been exposed to. Thus the use of laboratory testing to understand degradation of body armor is of interest to many agencies. Additionally, laboratory testing allows for the effect of variables to be investigated independently of each other, as well as in combination. The effect of inter-layer wear between apparel items and/or among layers of fabric within apparel does not appear to be systematically explored in the literature. In this paper, the effect of wear on (i) the tensile strength and (ii) the fragment protective performance of fabrics packs containing a para-aramid woven fabric typical of those used to manufacture body armor was investigated. © The Author(s) 2011.


McCluskie M.J.,Pfizer | Thorn J.,Pfizer | Gervais D.P.,Pfizer | Gervais D.P.,Porton Group | And 9 more authors.
International Immunopharmacology | Year: 2015

Anti-nicotine vaccines comprise nicotine-like haptens conjugated to a carrier protein plus adjuvant(s). Unfortunately, those tested clinically have failed to improve overall long term quit rates. We had shown in mice that carrier, hapten, linker, hapten load (number of haptens per carrier molecule), aggregation and adducts, as well as adjuvants influence the function of antibodies (Ab) induced. Herein, we tested an optimized antigen, NIC7-CRM, comprised of 5-aminoethoxy-nicotine (NIC7) conjugated to genetically detoxified diphtheria toxin (CRM197), with hapten load of ~ 16, no aggregation (~ 100% monomer) and minimal adducts. NIC7-CRM was tested in non-human primates (NHP) and compared to NIC-VLP, which has the same hapten and carrier as the clinical-stage CYT002-NicQb but a slightly different linker and lower hapten load. With alum as sole adjuvant, NIC7-CRM was superior to NIC-VLP for Ab titer, avidity and ex vivo function (83% and 27% nicotine binding at 40 ng/mL respectively), but equivalent for in vivo function after intravenous [IV] nicotine challenge (brain levels reduced ~ 10%). CpG adjuvant added to NIC7-CRM/alum further enhanced the Ab responses and both ex vivo function (100% bound) and in vivo function (~ 80% reduction in brain). Thus, both optimal antigen design and CpG adjuvant were required to achieve a highly functional vaccine. The compelling NHP data with NIC7-CRM with alum/CpG supported human testing, currently underway. © 2015 Elsevier Inc. All rights reserved.


PubMed | Porton Group
Type: Journal Article | Journal: Chemico-biological interactions | Year: 2016

The provision of effective Medical Countermeasures (MedCM) for all agents and routes of exposure is a strategic goal of defence research and development. In the case of military autoinjector-based therapies for nerve agent poisoning, current treatment effectiveness is limited by the oxime reactivator being effective against only certain agents, by rapid clearance times of the drugs and because the doses may not be optimal for treatment of severe poisoning. Prolonged poisoning by nerve agents entering the body through the skin is also challenging. Since casualty handling timelines have reduced significantly in recent years, it may be sufficient for first aid therapy to provide protection for only a few hours until further medical treatment is available. Therefore, the traditional evaluation of first aid therapy in animal models of survival at 24h may not be appropriate. At various echelons of medical care, further therapeutic interventions are possible. The current basis for the medical management of nerve-agent poisoned casualties is derived mainly from clinical experience with pesticide poisoning. Adjunct therapy with a bioscavenger (such as human butyrylcholinesterase (huBChE)), could have utility as a delayed intervention by reducing the toxic load. It has previously been demonstrated that huBChE is an effective post-exposure therapy against percutaneous VX poisoning. It is recommended that the scope of animal models of nerve agent MedCM are extended to cover evaluation of both first aid MedCM over significantly reduced timescales, and subsequent supportive therapeutic and medical management strategies over longer timescales. In addition to bioscavengers, these strategies could include repeated combined and individual therapy drugs to alleviate symptoms, other classes of drugs or ventilatory support. Crown Copyright


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