2,101 research outputs found
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Protective immunity elicited by recombinant bacille Calmette-Guerin (BCG) expressing outer surface protein A (OspA) lipoprotein: a candidate Lyme disease vaccine.
The current vaccine against tuberculosis, Mycobacterium bovis strain bacille Calmette-Guerin (BCG), offers potential advantages as a live, innately immunogenic vaccine vehicle for the expression and delivery of protective recombinant antigens (Stover, C.K., V.F. de la Cruz, T.R. Fuerst, J.E. Burlein, L.A. Benson, L.T. Bennett, G.P. Bansal, J.F. Young, M.H. Lee, G.F. Hatfull et al. 1991. Nature [Lond]. 351:456; Jacobs, W.R., Jr., S.B. Snapper, L. Lugosi and B.R. Bloom. 1990. Curr. Top. Microbiol. Immunol. 155:153; Jacobs, W.R., M. Tuckman, and B.R. Bloom. 1987. Nature [Lond.]. 327:532); but as an attenuated intracellular bacterium residing in macrophages, BCG would seem to be best suited for eliciting cellular responses and not humoral responses. Since bacterial lipoproteins are often among the most immunogenic of bacterial antigens, we tested whether BCG expression of a target antigen as a membrane-associated lipoprotein could enhance the potential for a recombinant BCG vaccine to elicit high-titered protective antibody responses to target antigens. Immunization of mice with recombinant BCG vaccines expressing the outer surface protein A (OspA) antigen of Borrelia burgdorferi as a membrane-associated lipoprotein resulted in protective antibody responses that were 100-1,000-fold higher than responses elicited by immunization with recombinant BCG expressing OspA cytoplasmically or as a secreted fusion protein. Furthermore, these improved antibody responses were observed in heterogeneous mouse strains that vary in their immune responsiveness to OspA and sensitivity to BCG growth. Thus, expression of protective antigens as chimeric membrane-associated lipoproteins on recombinant BCG may result in the generation of new candidate vaccines against Lyme borreliosis and other human or veterinary diseases where humoral immunity is the protective response
Improving public services through open data: public toilets
Bichard’s work for the TACT3 project (Bichard REF Output 3) found that UK toilet provision is not centrally collated and no national map or database of toilets exists. In contrast, the UK government’s white paper Open Public Services (2011) emphasised its commitment to incorporating the use of Open Data in public services provision that could be tailored to community preferences, and therefore be more sustainable. Incorporating Open Data on public toilet provision, Bichard and Knight (RCA) developed The Great British Public Toilet Map (GBPTM). Whilst a number of other websites and applications map toilets by ‘crowd surfing’, GBPTM is entirely populated by Open Data, and not only uses the data as information for users, but informs members of the public that such information is available and accessible for their use.
This paper presents the development of the GBPTM, including inclusive design research and studies that compare accuracy of information directly provided by users with Open Data collected by local authorities. It suggests that, to meet the health and well-being of an ageing population, a sustainable and cost-effective solution must be found for ‘publicly accessible’ toilet provision, including opening up provision beyond that ‘for customers only’ and providing accurate information on current public provision. The paper highlights the barriers encountered in the production of Open Data by local authorities. A review of the paper in the journal Civil Engineering (May 2013) described the design of the GBPTM as a ‘simple and elegant solution’.
The development of a digital output and an understanding of digitally based research led to Bichard’s successful submission to an EPSRC Digital Economy sandpit, in which she developed an interdisciplinary project with the Universities of Newcastle, Bournemouth and the West of England. The project, Family Rituals 2.0, secured £750,000 in research funding with Bichard as co-investigator (2013–15)
Evidence for folate-salvage reactions in plants
Folates in vivo undergo oxidative cleavage, giving pterin and p-aminobenzoylglutamate (pABAGlu) moieties. These breakdown products are excreted in animals, but their fate is unclear in microorganisms and unknown in plants. As indirect evidence from this and previous studies strongly suggests that plants can have high folate-breakdown rates (approximately 10% per day), salvage of the cleavage products seems likely. Four sets of observations support this possibility. First, cleavage products do not normally accumulate: pools of pABAGlu (including its polyglutamyl forms) are equivalent to, at most, 4-14% of typical total folate pools in Arabidopsis thaliana, Lycopersicon esculentum and Pisum sativum tissues. Pools of the pterin oxidation end-product pterin-6-carboxylate are, likewise, fairly small (3-37%) relative to total folate pools. Second, little pABAGlu built up in A. thaliana plantlets when net folate breakdown was induced by blocking folate synthesis with sulfanilamide. Third, A. thaliana and L. esculentum tissues readily converted supplied breakdown products to folate synthesis precursors: pABAGlu was hydrolysed to p-aminobenzoate and glutamate, and dihydropterin-6-aldehyde was reduced to 6-hydroxymethyldihydropterin. Fourth, both these reactions were detected in vitro; the reduction used NADPH as cofactor. An alternative salvage route for pABAGlu, direct reincorporation into dihydrofolate via the action of dihydropteroate synthase, appears implausible from the properties of this enzyme. We conclude that plants are excellent organisms in which to explore the biochemistry of folate salvage
Survey of the needs of patients with spinal cord injury: impact and priority for improvement in hand function in tetraplegics\ud
Objective: To investigate the impact of upper extremity deficit in subjects with tetraplegia.\ud
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Setting: The United Kingdom and The Netherlands.\ud
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Study design: Survey among the members of the Dutch and UK Spinal Cord Injury (SCI) Associations.\ud
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Main outcome parameter: Indication of expected improvement in quality of life (QOL) on a 5-point scale in relation to improvement in hand function and seven other SCI-related impairments.\ud
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Results: In all, 565 subjects with tetraplegia returned the questionnaire (overall response of 42%). Results in the Dutch and the UK group were comparable. A total of 77% of the tetraplegics expected an important or very important improvement in QOL if their hand function improved. This is comparable to their expectations with regard to improvement in bladder and bowel function. All other items were scored lower.\ud
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Conclusion: This is the first study in which the impact of upper extremity impairment has been assessed in a large sample of tetraplegic subjects and compared to other SCI-related impairments that have a major impact on the life of subjects with SCI. The present study indicates a high impact as well as a high priority for improvement in hand function in tetraplegics.\ud
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High-sensitivity diamond magnetometer with nanoscale resolution
We present a novel approach to the detection of weak magnetic fields that
takes advantage of recently developed techniques for the coherent control of
solid-state electron spin quantum bits. Specifically, we investigate a magnetic
sensor based on Nitrogen-Vacancy centers in room-temperature diamond. We
discuss two important applications of this technique: a nanoscale magnetometer
that could potentially detect precession of single nuclear spins and an optical
magnetic field imager combining spatial resolution ranging from micrometers to
millimeters with a sensitivity approaching few femtotesla/Hz.Comment: 29 pages, 4 figure
Quantum control of proximal spins using nanoscale magnetic resonance imaging
Quantum control of individual spins in condensed matter systems is an
emerging field with wide-ranging applications in spintronics, quantum
computation, and sensitive magnetometry. Recent experiments have demonstrated
the ability to address and manipulate single electron spins through either
optical or electrical techniques. However, it is a challenge to extend
individual spin control to nanoscale multi-electron systems, as individual
spins are often irresolvable with existing methods. Here we demonstrate that
coherent individual spin control can be achieved with few-nm resolution for
proximal electron spins by performing single-spin magnetic resonance imaging
(MRI), which is realized via a scanning magnetic field gradient that is both
strong enough to achieve nanometric spatial resolution and sufficiently stable
for coherent spin manipulations. We apply this scanning field-gradient MRI
technique to electronic spins in nitrogen-vacancy (NV) centers in diamond and
achieve nanometric resolution in imaging, characterization, and manipulation of
individual spins. For NV centers, our results in individual spin control
demonstrate an improvement of nearly two orders of magnitude in spatial
resolution compared to conventional optical diffraction-limited techniques.
This scanning-field-gradient microscope enables a wide range of applications
including materials characterization, spin entanglement, and nanoscale
magnetometry.Comment: 7 pages, 4 figure
An Experiment on Prediction Markets in Science
Prediction markets are powerful forecasting tools. They have the potential to aggregate private information, to generate and disseminate a consensus among the market participants, and to provide incentives for information acquisition. These market functionalities can be very valuable for scientific research. Here, we report an experiment that examines the compatibility of prediction markets with the current practice of scientific publication. We investigated three settings. In the first setting, different pieces of information were disclosed to the public during the experiment. In the second setting, participants received private information. In the third setting, each piece of information was private at first, but was subsequently disclosed to the public. An automated, subsidizing market maker provided additional incentives for trading and mitigated liquidity problems. We find that the third setting combines the advantages of the first and second settings. Market performance was as good as in the setting with public information, and better than in the setting with private information. In contrast to the first setting, participants could benefit from information advantages. Thus the publication of information does not detract from the functionality of prediction markets. We conclude that for integrating prediction markets into the practice of scientific research it is of advantage to use subsidizing market makers, and to keep markets aligned with current publication practice
An Ultra-High Discrimination Y Chromosome Short Tandem Repeat Multiplex DNA Typing System
In forensic casework, Y chromosome short tandem repeat markers (Y-STRs) are often used to identify a male donor DNA profile in the presence of excess quantities of female DNA, such as is found in many sexual assault investigations. Commercially available Y-STR multiplexes incorporating 12–17 loci are currently used in forensic casework (Promega's PowerPlex® Y and Applied Biosystems' AmpFlSTR® Yfiler®). Despite the robustness of these commercial multiplex Y-STR systems and the ability to discriminate two male individuals in most cases, the coincidence match probabilities between unrelated males are modest compared with the standard set of autosomal STR markers. Hence there is still a need to develop new multiplex systems to supplement these for those cases where additional discriminatory power is desired or where there is a coincidental Y-STR match between potential male participants. Over 400 Y-STR loci have been identified on the Y chromosome. While these have the potential to increase the discrimination potential afforded by the commercially available kits, many have not been well characterized. In the present work, 91 loci were tested for their relative ability to increase the discrimination potential of the commonly used ‘core’ Y-STR loci. The result of this extensive evaluation was the development of an ultra high discrimination (UHD) multiplex DNA typing system that allows for the robust co-amplification of 14 non-core Y-STR loci. Population studies with a mixed African American and American Caucasian sample set (n = 572) indicated that the overall discriminatory potential of the UHD multiplex was superior to all commercial kits tested. The combined use of the UHD multiplex and the Applied Biosystems' AmpFlSTR® Yfiler® kit resulted in 100% discrimination of all individuals within the sample set, which presages its potential to maximally augment currently available forensic casework markers. It could also find applications in human evolutionary genetics and genetic genealogy
Experimental loophole-free violation of a Bell inequality using entangled electron spins separated by 1.3 km
For more than 80 years, the counterintuitive predictions of quantum theory
have stimulated debate about the nature of reality. In his seminal work, John
Bell proved that no theory of nature that obeys locality and realism can
reproduce all the predictions of quantum theory. Bell showed that in any local
realist theory the correlations between distant measurements satisfy an
inequality and, moreover, that this inequality can be violated according to
quantum theory. This provided a recipe for experimental tests of the
fundamental principles underlying the laws of nature. In the past decades,
numerous ingenious Bell inequality tests have been reported. However, because
of experimental limitations, all experiments to date required additional
assumptions to obtain a contradiction with local realism, resulting in
loopholes. Here we report on a Bell experiment that is free of any such
additional assumption and thus directly tests the principles underlying Bell's
inequality. We employ an event-ready scheme that enables the generation of
high-fidelity entanglement between distant electron spins. Efficient spin
readout avoids the fair sampling assumption (detection loophole), while the use
of fast random basis selection and readout combined with a spatial separation
of 1.3 km ensure the required locality conditions. We perform 245 trials
testing the CHSH-Bell inequality and find . A
null hypothesis test yields a probability of that a local-realist
model for space-like separated sites produces data with a violation at least as
large as observed, even when allowing for memory in the devices. This result
rules out large classes of local realist theories, and paves the way for
implementing device-independent quantum-secure communication and randomness
certification.Comment: Raw data will be made available after publicatio
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Medium-term seed storage of 50 genera of forage legumes and evidence-based genebank monitoring intervals
Genebanks maintaining seeds for long-term genetic resources conservation monitor seed lots to detect early loss in viability. Monitoring is costly and depletes valuable seed. Three decades of genebank seed germination test results of diverse forage species from 50 legume genera in the International Livestock Research Institute’s medium-term store (circa 8° C with 5 % moisture content) were analysed to determine whether advice on seed monitoring intervals could be derived. Cumulative normal distributions were fitted by probit analysis for each seed lot and compared within each genus. Six patterns of within-genus variation were identified: no detectable trend in germination test results during storage (4 genera); detectable trends, but variable (positive to negative) amongst lots (5); consistent slope of loss in viability amongst lots (17); consistent slope of increase in ability to germinate amongst lots (21); common loss in viability amongst lots (2); common increase in ability to germinate amongst lots (1). Seed lot monitoring intervals for the medium-term store were derived for each of 19 genera with consistent loss in viability across seed lots: three genera provided comparatively rapid deterioration, five met the general expectations for a medium-term store (2-10 years’ maintenance of high viability), whilst 11 provided much better survival. Moreover, 26 further genera provided no evidence as yet of seed deterioration; of these, 22 improved in ability to germinate during storage indicating confounding of hardseededness with viability in germination tests
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