Tetrahydrobiopterin analogues with NO-dependent pulmonary vasodilator properties

Reduced NO levels due to the deficiency of tetrahydrobiopterin (BH4) contribute to impaired vasodilation in pulmonary hypertension Due to the chemically unstable nature of BH4 it was hypothesised that oxidatively stable analogues of BR, would be able to support NO synthesis to improve Endothelial dysfunction in pulmonary hypertension Two analogues of BH4 namely 6-hydroxymethyl pterin (HMP) and 6-acetyl 7 7-dimethyl 7 8-dihydropterin (ADDP) were evaluated for vasodilator activity on precontracted rat pulmonary artery rings ADDP was administered to pulmonary hypertensive rats followed by measurement of pulmonary vascular resistance in perfused lungs and eNOS expression by immunohistochemistry ADDP and HMP caused significant relaxation in vitro in rat pulmonary arteries depleted of BH4 with a maximum relaxation at 0 3 mu M (both P<005) Vasodilator activity of ADDP and HMP was completely abolished following preincubation with the NO synthase inhibitor L-NAME ADDP and HMP did not alter relaxation induced by carbachol or spermine NONOate BH4 Itself did not produce relaxation In rats receiving ADDP 141 mg/kg/day pulmonary vasodilation induced by calcium ionophore A23187 was augmented and eNOS immunoreactivity was increased In conclusion ADDP and HMP are two analogues of BH4 which can act as oxidatively stable alternatives to BH4 in causing NO-mediated vasorelaxation Chronic treatment with ADDP resulted in Improvement of NO-mediated pulmonary artery dilation and enhanced expression of eNOS in the pulmonary vascular endothelium Chemically stable analogue, of BH4 may be able to limit endothelial dysfunction in the pulmonary vasculatur

Experimental Realization of a One-way Quantum Computer Algorithm Solving Simon's Problem

We report an experimental demonstration of a one-way implementation of a quantum algorithm solving Simon's Problem - a black box period-finding problem which has an exponential gap between the classical and quantum runtime. Using an all-optical setup and modifying the bases of single-qubit measurements on a five-qubit cluster state, key representative functions of the logical two-qubit version's black box can be queried and solved. To the best of our knowledge, this work represents the first experimental realization of the quantum algorithm solving Simon's Problem. The experimental results are in excellent agreement with the theoretical model, demonstrating the successful performance of the algorithm. With a view to scaling up to larger numbers of qubits, we analyze the resource requirements for an n-qubit version. This work helps highlight how one-way quantum computing provides a practical route to experimentally investigating the quantum-classical gap in the query complexity model.Comment: 9 pages, 5 figure

Development of a liquid chromatography tandem mass spectrometry method for the simultaneous measurement of voriconazole, posaconazole and itraconazole

Background Azole-based antifungals are the first-line therapy for some of the most common mycoses and are now also being used prophylactically to protect immunocompromised patients. However, due to variability in both their metabolism and bioavailability, therapeutic drug monitoring is essential to avoid toxicity but still gain maximum efficacy. Methods Following protein precipitation of serum with acetonitrile, 20  µL of extract was injected onto a 2.1 × 50 mm Waters Atlantis dC18 3  µm column. Detection was via a Waters Quattro Premier XE tandem mass spectrometer operating in ESI-positive mode. Multiple reaction monitoring (MRM) detected two product ions for each compound and one for each isotopically labelled internal standard. Ion suppression, linearity, stability, matrix effects, recovery, imprecision, lower limits of measuring interval and detection were all assessed. Results Optimal chromatographic separation was achieved using gradient elution over 8 minutes. Voriconazole, posaconazole and itraconazole eluted at 1.71, 2.73 and 3.41 min, respectively. The lower limits of measuring interval for all three compounds was 0.1 mg/L. The assay was linear to 10 mg/L for voriconazole (R2 = 0.995) and 5 mg/L for posaconazole (R2 = 0.990) and itraconazole (R2 = 0.991). The assay was both highly accurate and precise with % bias of voriconazole, posaconazole and itraconazole, respectively, when compared with previous NEQAS samples. The intra-assay precision (CV%) was 1.6%, 2.5% and 1.9% for voriconazole, posaconazole and itraconazole, respectively, across the linear range. Conclusion A simple and robust method has been validated for azole antifungal therapeutic drug monitoring. This new assay will result in a greatly improved sample turnaround time and will therefore vastly increase the clinical utility of azole antifungal drug monitoring. </jats:sec

An All Optical Fibre Quantum Controlled-NOT Gate

We report the first experimental demonstration of an optical controlled-NOT gate constructed entirely in fibre. We operate the gate using two heralded optical fibre single photon sources and find an average logical fidelity of 90% and an average process fidelity of 0.83<F<0.91. On the basis of a simple model we are able to conclude that imperfections are primarily due to the photon sources, meaning that the gate itself works with very high fidelity.Comment: 4 pages, 4 figures, comments welcom

Experimental demonstration of a graph state quantum error-correction code

Scalable quantum computing and communication requires the protection of quantum information from the detrimental effects of decoherence and noise. Previous work tackling this problem has relied on the original circuit model for quantum computing. However, recently a family of entangled resources known as graph states has emerged as a versatile alternative for protecting quantum information. Depending on the graph's structure, errors can be detected and corrected in an efficient way using measurement-based techniques. In this article we report an experimental demonstration of error correction using a graph state code. We have used an all-optical setup to encode quantum information into photons representing a four-qubit graph state. We are able to reliably detect errors and correct against qubit loss. The graph we have realized is setup independent, thus it could be employed in other physical settings. Our results show that graph state codes are a promising approach for achieving scalable quantum information processing

Modelling arterial wall drug concentrations following the insertion of a drug-eluting stent

A mathematical model of a drug-eluting stent is proposed. The model considers a polymer region, containing the drug initially, and a porous region consisting of smooth muscle cells embedded in an extracellular matrix. An analytical solution is obtained for the drug concentration both in the target cells and the interstitial region of the tissue in terms of the drug release concentration at the interface between the polymer and the tissue. When the polymer region and the tissue region are considered as a coupled system it can be shown, under certain assumptions, that the drug release concentration satisfies a Volterra integral equation which must be solved numerically in general. The drug concentrations, both in the cellular and extracellular regions, are then determined from the solution of this integral equation and used in deriving the mass of drug in the cells and extracellular space

Experimental characterization of photonic fusion using fiber sources

We report the fusion of photons from two independent photonic crystal fiber sources into polarization entangled states using a fiber-based polarizing beam splitter. We achieve fidelities of up to F = 0.74 $\pm$ 0.01 with respect to the maximally entangled Bell state \phi+ using a low pump power of 5.3mW with a success rate of 3.2 four-fold detections per second. By increasing the pump power we find that success rates of up to 111.6 four-folds per second can be achieved, with entanglement still present in the fused state. We characterize the fusion operation by providing a full quantum process reconstruction. Here a model is developed to describe the generation of entanglement, including the main causes of imperfection, and we show that this model fits well with the experimental results. Our work shows how non-ideal settings limit the success of the fusion, providing useful information about the practical requirements for an operation that may be used to build large entangled states in bulk and on-chip quantum photonic waveguides.Comment: 19 pages, 4 figure

Experimental characterization of universal one-way quantum computing

We report the characterization of a universal set of logic gates for one-way quantum computing using a four-photon 'star' cluster state generated by fusing photons from two independent photonic crystal fibre sources. We obtain a fidelity for the cluster state of 0.66 ± 0.01 with respect to the ideal case. We perform quantum process tomography to completely characterize a controlled-NOT, Hadamard and T gate all on the same compact entangled resource. Together, these operations make up a universal set of gates such that arbitrary quantum logic can be efficiently constructed from combinations of them. We find process fidelities with respect to the ideal cases of 0.64 ± 0.01 for the CNOT, 0.67 ± 0.03 for the Hadamard and 0.76 ± 0.04 for the T gate. The characterization of these gates enables the simulation of larger protocols and algorithms. As a basic example, we simulate a Swap gate consisting of three concatenated CNOT gates. Our work provides some pragmatic insights into the prospects for building up to a fully scalable and fault-tolerant one-way quantum computer with photons in realistic conditions

Boundary conditions at a fluid - solid interface

We study the boundary conditions at a fluid-solid interface using molecular dynamics simulations covering a broad range of fluid-solid interactions and fluid densities, and both simple and chain-molecule fluids. The slip length is shown to be independent of the type of flow, but rather is related to the fluid organization near the solid, as governed by the fluid-solid molecular interactions.Comment: REVtex, to appear in Physical Review Letter

Disruption of host-seeking behaviour by the salmon louse,Lepeophtheirus salmonis,using botanically derived repellents

The potential for developing botanically derived natural products as novel feed-through repellents for disrupting settlement of the salmon louse, Lepeophtheirus salmonis (Caligidae) upon farmed Atlantic salmon, Salmo salar, was investigated using an established laboratory vertical Y-tube behavioural bioassay for assessing copepodid behaviour. Responses to artificial sea water conditioned with the odour of salmon, or to the known salmon-derived kairomone component, α-isophorone, in admixture with selected botanical materials previously known to interfere with invertebrate arthropod host location were recorded. Materials included oils extracted from garlic, Allium sativum (Amaryllidaceae), rosemary, Rosmarinus officinalis (Lamiaceae), lavender, Lavandula angustifolia (Lamiaceae), and bog myrtle, Myrica gale (Myricaceae), and individual components (diallyl sulphide and diallyl disulphide from garlic; allyl, propyl, butyl, 4-pentenyl and 2-phenylethyl isothiocyanate from plants in the Brassica genus). Removal of attraction to salmon-conditioned water (SCW) or α-isophorone was observed when listed materials were presented at extremely low parts per trillion (ppt), that is picograms per litre or 10−12 level. Significant masking of attraction to SCW was observed at a level of 10 ppt for diallyl disulphide and diallyl sulphide, and allyl isothiocyanate and butyl isothiocyanate. The potential of very low concentrations of masking compounds to disrupt Le. salmonis copepodid settlement on a host fish has been demonstrated in vitro