156 research outputs found

    The Modernization of the Autopsy: Application of Ultrastructural and Biochemical Methods to Human Disease

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    The autopsy has provided, and still provides, the stimulus for many attempts to reproduce disease in experimental animal models. This approach has become increasingly difficult, however, in the case of human disease, principally shock. The study of some pathological states in animal models requires testing in several species and final confirmation in man before this knowledge can be applied to living patients. In our studies the application of cell biology techniques at autopsy has permitted the generation of new hypotheses which are more amenable to further exploration in experimental models and can be more precisely related to human disease

    Delivering strong 1H nuclear hyperpolarization levels and long magnetic lifetimes through signal amplification by reversible exchange

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    Hyperpolarization turns typically weak NMR and MRI responses into strong signals so that ordinarily impractical measurements become possible. The potential to revolutionize analytical NMR and clinical diagnosis through this approach reflect this area's most compelling outcomes. Methods to optimize the low cost parahydrogen based approach signal amplification by reversible exchange (SABRE) with studies on a series of biologically relevant nicotinamides and methyl nicotinates are detailed. These procedures involve specific 2H-labelling in both the agent and catalyst and achieve polarization lifetimes of ca. 2 minutes with 50% polarization in the case of 4,6-d2-methylnicotinate. As a 1.5 T hospital scanner has an effective 1H polarization level of just 0.0005% this strategy should result in compressed detection times for chemically discerning measurements that probe disease. To demonstrate this techniques generality, we exemplify further studies on a range of pyridazine, pyrimidine, pyrazine and isonicotinamide analogues that feature as building blocks in biochemistry and many disease treating drugs

    Strongly hyperpolarized gas from parahydrogen by rational design of ligand-capped nanoparticles

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    The production of hyperpolarized fluids in continuous mode would broaden substantially the range of applications in chemistry, materials science, and biomedicine. Here we show that the rational design of a heterogeneous catalyst based on a judicious choice of metal type, nanoparticle size and surface decoration with appropriate ligands leads to highly efficient pairwise addition of dihydrogen across an unsaturated bond. This is demonstrated in a parahydrogen-induced polarization (PHIP) experiment by a 508-fold enhancement (±78) of a CH3 proton signal and a corresponding 1219-fold enhancement (±187) of a CH2 proton signal using nuclear magnetic resonance (1H-NMR). In contrast, bulk metal catalyst does not show this effect due to randomization of reacting dihydrogen. Our approach results in the largest gas-phase NMR signal enhancement by PHIP known to date. Sensitivity-enhanced NMR with this technique could be used to image microfluidic reactions in-situ, to probe nonequilibrium thermodynamics or for the study of metabolic reactions

    Improving the hyperpolarization of (31)p nuclei by synthetic design

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    Traditional (31)P NMR or MRI measurements suffer from low sensitivity relative to (1)H detection and consequently require longer scan times. We show here that hyperpolarization of (31)P nuclei through reversible interactions with parahydrogen can deliver substantial signal enhancements in a range of regioisomeric phosphonate esters containing a heteroaromatic motif which were synthesized in order to identify the optimum molecular scaffold for polarization transfer. A 3588-fold (31)P signal enhancement (2.34% polarization) was returned for a partially deuterated pyridyl substituted phosphonate ester. This hyperpolarization level is sufficient to allow single scan (31)P MR images of a phantom to be recorded at a 9.4 T observation field in seconds that have signal-to-noise ratios of up to 94.4 when the analyte concentration is 10 mM. In contrast, a 12 h 2048 scan measurement under standard conditions yields a signal-to-noise ratio of just 11.4. (31)P-hyperpolarized images are also reported from a 7 T preclinical scanner

    Automatic Detection of User Abilities through the SmartAbility Framework

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    This paper presents a proposed smartphone application for the unique SmartAbility Framework that supports interaction with technology for people with reduced physical ability, through focusing on the actions that they can perform independently. The Framework is a culmination of knowledge obtained through previously conducted technology feasibility trials and controlled usability evaluations involving the user community. The Framework is an example of ability-based design that focuses on the abilities of users instead of their disabilities. The paper includes a summary of Versions 1 and 2 of the Framework, including the results of a two-phased validation approach, conducted at the UK Mobility Roadshow and via a focus group of domain experts. A holistic model developed by adapting the House of Quality (HoQ) matrix of the Quality Function Deployment (QFD) approach is also described. A systematic literature review of sensor technologies built into smart devices establishes the capabilities of sensors in the Android and iOS operating systems. The review defines a set of inclusion and exclusion criteria, as well as search terms used to elicit literature from online repositories. The key contribution is the mapping of ability-based sensor technologies onto the Framework, to enable the future implementation of a smartphone application. Through the exploitation of the SmartAbility application, the Framework will increase technology amongst people with reduced physical ability and provide a promotional tool for assistive technology manufacturers
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