21 research outputs found

    High-fidelity phase and amplitude control of phase-only computer generated holograms using conjugate gradient minimisation

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    Funding: Leverhulme Trust (RPG-2013-074); EPSRC (EP/G03673X/1; EP/L015110/1).We demonstrate simultaneous control of both the phase and amplitude of light using a conjugate gradient minimisation-based hologram calculation technique and a single phase-only spatial light modulator (SLM). A cost function, which incorporates the inner product of the light field with a chosen target field within a defined measure region, is efficiently minimised to create high fidelity patterns in the Fourier plane of the SLM. A fidelity of F = 0.999997 is achieved for a pattern resembling an LG01 mode with a calculated light-usage efficiency of 41.5%. Possible applications of our method in optical trapping and ultracold atoms are presented and we show uncorrected experimental realisation of our patterns with F = 0.97 and 7.8% light efficiency.Publisher PDFPeer reviewe

    Global Analysis of Small Molecule Binding to Related Protein Targets

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    We report on the integration of pharmacological data and homology information for a large scale analysis of small molecule binding to related targets. Differences in small molecule binding have been assessed for curated pairs of human to rat orthologs and also for recently diverged human paralogs. Our analysis shows that in general, small molecule binding is conserved for pairs of human to rat orthologs. Using statistical tests, we identified a small number of cases where small molecule binding is different between human and rat, some of which had previously been reported in the literature. Knowledge of species specific pharmacology can be advantageous for drug discovery, where rats are frequently used as a model system. For human paralogs, we demonstrate a global correlation between sequence identity and the binding of small molecules with equivalent affinity. Our findings provide an initial general model relating small molecule binding and sequence divergence, containing the foundations for a general model to anticipate and predict within-target-family selectivity

    Baseline characteristics of patients in the reduction of events with darbepoetin alfa in heart failure trial (RED-HF)

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    <p>Aims: This report describes the baseline characteristics of patients in the Reduction of Events with Darbepoetin alfa in Heart Failure trial (RED-HF) which is testing the hypothesis that anaemia correction with darbepoetin alfa will reduce the composite endpoint of death from any cause or hospital admission for worsening heart failure, and improve other outcomes.</p> <p>Methods and results: Key demographic, clinical, and laboratory findings, along with baseline treatment, are reported and compared with those of patients in other recent clinical trials in heart failure. Compared with other recent trials, RED-HF enrolled more elderly [mean age 70 (SD 11.4) years], female (41%), and black (9%) patients. RED-HF patients more often had diabetes (46%) and renal impairment (72% had an estimated glomerular filtration rate <60 mL/min/1.73 m2). Patients in RED-HF had heart failure of longer duration [5.3 (5.4) years], worse NYHA class (35% II, 63% III, and 2% IV), and more signs of congestion. Mean EF was 30% (6.8%). RED-HF patients were well treated at randomization, and pharmacological therapy at baseline was broadly similar to that of other recent trials, taking account of study-specific inclusion/exclusion criteria. Median (interquartile range) haemoglobin at baseline was 112 (106–117) g/L.</p> <p>Conclusion: The anaemic patients enrolled in RED-HF were older, moderately to markedly symptomatic, and had extensive co-morbidity.</p&gt

    G protein-dependent pharmacology of histamine H3 receptor ligands: Evidence for heterogeneous active state receptor conformations

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    ABSTRACT Previously reported pharmacological studies using the imidazole-containing histamine H 3 receptor ligands GT-2331 (Cipralisant) and proxyfan resulted in a range of classifications (antagonist, agonist, and protean) for these compounds. We examined the role that the signaling system, with particular emphasis on the type of G protein, had on the pharmacology observed for H 3 ligands. Ligands were assessed using assays measuring neurotransmitter release, cAMP, and guanosine 5Ј- binding. Whereas clobenpropit and ciproxifan were consistently antagonists, GT-2331, proxyfan, and imetit exhibited differential activity. Although GT-2331 and proxyfan exhibited little agonist activity in neurotransmitter release assays, both demonstrated full agonism relative to (R)-␣-methylhistamine in cAMP assays. In [ 35 S]GTP␥S binding assays, GT-2331 and proxyfan demonstrated partial agonism. Imetit showed full agonism in most assays, but it was slightly less efficacious in a neurotransmitter release assay and in [ 35 S]GTP␥S binding at the human H 3 receptor. To further examine these ligands, we coexpressed G␣16 or chimeric G␣q/i 5 in human embryonic kidney cells expressing the human H 3 receptor and assayed intracellular calcium and cAMP levels. GT-2331, proxyfan, and imetit demonstrated full agonism in all assays of cAMP activity. However, in cells expressing G␣16, they exhibited minimal agonism in calcium mobilization assays, whereas imetit showed partial agonism. When G␣q/i 5 was used, the activity of both GT-2331 and proxyfan increased, whereas imetit became a full agonist. These results demonstrate that GT-2331 and proxyfan's differential pharmacology at the H 3 receptor depends on the type of G protein used and provide indirect evidence for differential ligand-bound active states that mediate signaling by the H 3 receptor

    Data underpinning High-fidelity phase and amplitude control of phase-only computer generated holograms using conjugate gradient minimisation

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    Data underpinning: D. Bowman, T. L. Harte, V. Chardonnet, C. De Groot, S. J. Denny, G. Le Goc, M. Anderson, P. Ireland, D. Cassettari, & G. D. Bruce, "High-fidelity phase and amplitude control of phase-only computer generated holograms using conjugate gradient minimisation" Opt. Express 25, 11692-11700 (2017) https://www.osapublishing.org/oe/abstract.cfm?uri=oe-25-10-11692 The algorithm used in the work may be found on github, see link. Codes may be used freely, but please cite the above article

    Characterization of Elliptic Curve Traces under FR-reduction

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    Elliptic curve cryptosystems([19],[25]) are based on the elliptic curve discrete logarithm problem(ECDLP). If elliptic curve cryptosystems avoid FR-reduction([11],[17]) and anomalous elliptic curve over F_q ([34],[3],[36]), then with current knowledge we can construct elliptic curve cryptosystems over a smaller definition field. ECDLP has an interesting property that the security deeply depends on elliptic curve traces rather than definition fields, which does not occur in the case of the discrete logarithm problem(DLP). Therefore it is important to characterize elliptic curve traces explicitly from the security point of view. As for FR-reduction, supersingular elliptic curves or elliptic curve E/F_q with trace 2 have been reported to be vulnerable. However unfortunately these have been only results that characterize elliptic curve traces explicitly for FR- or MOV-reductions. More importantly, the secure trace against FR- reduction has not been reported at all. Elliptic curves with the secure trace means that the reduced extension degree is always higher than a certain level. In this paper, we aim at characterizing elliptic curve traces by FR-reduction and investigate explicit conditions of traces vulnerable or secure against FR-reduction. We show new explicit conditions of elliptic curve traces for FR-reduction. We also present algorithms to construct such elliptic curves, which have relation to famous number theory problems.Information security and cryptology - ICISC 2000 : third International Conference, Seoul, Korea, December 8-9, 2000 : proceedings / Dongho Won (ed.)
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