8,980 research outputs found

    Potential P-Glycoprotein-Mediated Drug-Drug Interactions of Antimalarial Agents in Caco-2 cells

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    Antimalarials are widely used in African and Southeast Asian countries, where they are combined with other drugs for the treatment of concurrent ailments. The potential for P-glycoprotein (P-gp)-mediated drug-drug interactions (DDIs) between antimalarials and P-gp substrates was examined using a Caco-2 cell-based model. Selected antimalarials were initially screened for their interaction with P-gp based on the inhibition of rhodamine-123 (Rho-123) transport in Caco-2 cells. Verapamil (100 mM) and quinidine (1 mM) were used as positive inhibition controls. Lumefantrine, amodiaquin, and artesunate all showed blockade of Rho-123 transport. Subsequently, the inhibitory effect of these antimalarials on the bi-directional passage of digoxin (DIG) was examined. All of the drugs decreased basal-toapical (B-A) P-gp-mediated DIG transport at concentrations of 100 mM and 1 mM. These concentrations may reflect therapeutic doses for amodiaquin and artesunate. Therefore, clinically relevant DDIs may occur between certain antimalarials and P-gp substrates in general

    The inner automorphism 3-group of a strict 2-group

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    Any group GG gives rise to a 2-group of inner automorphisms, INN(G)\mathrm{INN}(G). It is an old result by Segal that the nerve of this is the universal GG-bundle. We discuss that, similarly, for every 2-group G(2)G_{(2)} there is a 3-group INN(G(2))\mathrm{INN}(G_{(2)}) and a slightly smaller 3-group INN0(G(2))\mathrm{INN}_0(G_{(2)}) of inner automorphisms. We describe these for G(2)G_{(2)} any strict 2-group, discuss how INN0(G(2))\mathrm{INN}_0(G_{(2)}) can be understood as arising from the mapping cone of the identity on G(2)G_{(2)} and show that its underlying 2-groupoid structure fits into a short exact sequence G(2)INN0(G(2))ΣG(2)G_{(2)} \to \mathrm{INN}_0(G_{(2)}) \to \Sigma G_{(2)}. As a consequence, INN0(G(2))\mathrm{INN}_0(G_{(2)}) encodes the properties of the universal G(2)G_{(2)} 2-bundle.Comment: references added, relation to simplicial constructions expanded, version to appear in JHR

    Spin Calogero models associated with Riemannian symmetric spaces of negative curvature

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    The Hamiltonian symmetry reduction of the geodesics system on a symmetric space of negative curvature by the maximal compact subgroup of the isometry group is investigated at an arbitrary value of the momentum map. Restricting to regular elements in the configuration space, the reduction generically yields a spin Calogero model with hyperbolic interaction potentials defined by the root system of the symmetric space. These models come equipped with Lax pairs and many constants of motion, and can be integrated by the projection method. The special values of the momentum map leading to spinless Calogero models are classified under some conditions, explaining why the BCnBC_n models with two independent coupling constants are associated with SU(n+1,n)/S(U(n+1)×U(n))SU(n+1,n)/S(U(n+1)\times U(n)) as found by Olshanetsky and Perelomov. In the zero curvature limit our models reproduce rational spin Calogero models studied previously and similar models correspond to other (affine) symmetric spaces, too. The construction works at the quantized level as well.Comment: 26 pages, v3: final version with a remark added after equation (5.3

    Derivations of the trigonometric BC(n) Sutherland model by quantum Hamiltonian reduction

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    The BC(n) Sutherland Hamiltonian with coupling constants parametrized by three arbitrary integers is derived by reductions of the Laplace operator of the group U(N). The reductions are obtained by applying the Laplace operator on spaces of certain vector valued functions equivariant under suitable symmetric subgroups of U(N)\times U(N). Three different reduction schemes are considered, the simplest one being the compact real form of the reduction of the Laplacian of GL(2n,C) to the complex BC(n) Sutherland Hamiltonian previously studied by Oblomkov.Comment: 30 pages, LateX; v2: final version with minor stylistic modification

    The classification of substance and behavioural addictions: A preliminary investigation

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    The term addiction has been used to refer to impaired control over substance use for several centuries however recently there has been a shift toward using this term in the context of non-substance use disorders, such as pathological gambling. A preliminary investigation was conducted in an attempt to clarify the most appropriate classification of 'behavioural addictions'. Participants with alcohol dependence (AD, n = 24), pathological gambling (PG, n = 20) and compulsive buying disorder (CBD, n = 14) completed an Addictive Disorder Questionnaire (ADQ); the Symptom Checklist 90 Revised (SCL-90R); Barratt Impulsivity Scale II; and substance specific adaptations of the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). Although the AD group reported more severe addiction symptoms and had higher levels of depression and anxiety, there were broad similarities across the three disorders in relation to cravings, dyscontrol, impulsivity and obsessions. Despite the small sample size and the different recruitment strategies used across the groups, the findings from this preliminary study provide support for broadening addiction diagnostic definitions to include non-substance related disorders which in turn may contribute to the development of more efficacious treatments

    Un-reduction

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    This paper provides a full geometric development of a new technique called un-reduction, for dealing with dynamics and optimal control problems posed on spaces that are unwieldy for numerical implementation. The technique, which was originally concieved for an application to image dynamics, uses Lagrangian reduction by symmetry in reverse. A deeper understanding of un-reduction leads to new developments in image matching which serve to illustrate the mathematical power of the technique.Comment: 25 pages, revised versio
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