Interaction of the mu-opioid receptor with GPR177 (Wntless) inhibits Wnt secretion: potential implications for opioid dependence

Background  

Opioid agonist drugs produce analgesia. However, long-term exposure to opioid agonists may lead to opioid dependence. The analgesic and addictive properties of opioid agonist drugs are mediated primarily via the mu-opioid receptor (MOR). Opioid agonists appear to alter neuronal morphology in key brain regions implicated in the development of opioid dependence. However, the precise role of the MOR in the development of these neuronal alterations remains elusive. We hypothesize that identifying and characterizing novel MOR interacting proteins (MORIPs) may help to elucidate the underlying mechanisms involved in the development of opioid dependence.     

Ruthenium half-sandwich complexes as protein kinase inhibitors: an N-succinimidyl ester for rapid derivatizations of the cyclopentadienyl moiety

Cyclopentadienyl half-sandwich ruthenium complexes have been demonstrated to be promising scaffolds as protein kinase inhibitors. In order to rapidly identify derivatives which display modified pharmacological properties, we developed the synthesis of an organoruthenium compound bearing an N-succinimidyl ester at the cyclopentadienyl moiety. The quenching of this activated ester with a library of primary amines, followed by testing of the resulting amide library, led to the identification of organometallic Pim-1 and GSK-3 inhibitors with improved potencies and kinase selectivities. [structure: see text].     

High precision delta(17)O isotope measurements of oxygen from silicates and other oxides: method and applications

The use of infrared laser-assisted fluorination to release oxygen from milligram quantities of silicates or other oxide mineral grains is a well-established technique. However, relatively few studies have reported the optimisation of this procedure for oxygen-17 isotope measurements. We describe here details of an analytical system using infrared (10 μm) laser-assisted fluorination, in conjunction with a dual inlet mass spectrometer of high resolving power ( approximately 250) to provide (17)O and (18)O oxygen isotope measurements from 0.5-2 mg of silicates or other oxide mineral grains. Respective precisions (1) of typically 0.08 and 0.04 per thousand are obtained for the complete analytical procedure. Departures from the mass-dependent oxygen isotope fractionation line are quantified by Delta(17)O; our precision (1) of such measurements on individual samples is shown to be +/-0.024 per thousand. In turn, this permits the offset between parallel, mass-dependent fractionation lines to be characterised to substantially greater precision than has been possible hitherto. Application of this system to investigate the (17)O versus (18)O relationship for numerous terrestrial whole-rock and mineral samples, of diverse geological origins and age, indicates that the complete data set may be described by a single, mass-dependent fractionation line of slope 0.5244+/- 0.00038 (standard error). Copyright 1999 John Wiley & Sons, Ltd.     

Test of bell’s inequality using the one-atom micromaser

We examine a local realist bound in the case of a one-atom micromaser. It is shown that such a bound is violated using a simplified treatment of the micromaser. We consider the effect of dissipation in a proposed experiment with the real micromaser. It is seen that the magnitude of violation of a Bell-type inequality depends significantly on the cavity parameters.     

Finding the projection of a point onto the intersection of convex sets via projections onto half-spaces

We present a modification of Dykstra's algorithm which allows us to avoid projections onto general convex sets. Instead, we calculate projections onto either a half-space or onto the intersection of two half-spaces. Convergence of the algorithm is established and special choices of the half-spaces are proposed.The option to project onto half-spaces instead of general convex sets makes the algorithm more practical. The fact that the half-spaces are quite general enables us to apply the algorithm in a variety of cases and to generalize a number of known projection algorithms.The problem of projecting a point onto the intersection of closed convex sets receives considerable attention in many areas of mathematics and physics as well as in other fields of science and engineering such as image reconstruction from projections.In this work we propose a new class of algorithms which allow projection onto certain super half-spaces, i.e., half-spaces which contain the convex sets. Each one of the algorithms that we present gives the user freedom to choose the specific super half-space from a family of such half-spaces. Since projecting a point onto a half-space is an easy task to perform, the new algorithms may be more useful in practical situations in which the construction of the super half-spaces themselves is not too difficult.     

Preemptive expediting to improve project due date performance

Project expediting is often viewed as a corrective action taken in response to prior scheduling errors and is usually applied in the later stages of projects when it appears that predefined due dates will not be met. However, large-scale projects with uncertain activity durations tend to have numerous probabilistic network paths with complex interactions that require some level of expediting to ensure successful scheduling outcomes. Because potential expediting options are consumed over time, delaying expediting efforts until the later stages of projects is likely to result in higher expediting costs or poorer due date performance. This research introduces a preemptive expediting approach that evaluates the probability of completion before the due date throughout the life of a project and selects expediting options per a prespecified probability tolerance or expediting budget. An experiment demonstrates the benefits of this preemptive approach.     

Solutes in sulphuric acid—V : Effects of substituents on the ionization of benzenesulphonic acids

The ionization of the three isomeric aniliniumsulphonic acids and m-trimethylammoniumbenzenesulphonic acid has been measured by UV techniques. The ionizations are governed by the benzophenone acidity function H_o^a. The ionization of the aniliniumsulphonic acids studied involves the oxygen bonded hydrogen. Substituent effects on the ionization are small (p =0·7±0-1).     

Poincaré gauge invariance and the dynamical role of spin in gravitational theory

We classify, according to the number of independent gauge fields, Poincaré gauge invariant theoretical frameworks of describing gravity into three categories. One of them may provide the dynamical definition of the spin tensor S and that of the energy-momentum tensor T, resulting in the response equation of matter to gravity with the gravitational field strengths, D′ and F, coupled to the former tensors

$\text{T}{}_{\mathrm{\nu }}{}^{\mathrm{\mu }}\text{;}{}_{\mathrm{\mu }}\text{=D′}{}_{\mathrm{\mu \lambda \nu }}\text{T}{}^{\mathrm{\mu \lambda }}\text{+F}{}_{\mathrm{\mu \lambda \nu \rho }}\text{S}{}^{\mathrm{\rho \mu \lambda }}$

, where the right-hand side represents spin force densities. In the absence of spin the response reduces to the conventional one of general relativity, i.e., without the spin forces. For the electromagnetic field the phase-gauge invariance requires the same conclusion as for a scalar field. For a spin $\text{1}\text{2}$ particle there is torsion, which deflects its trajectory from geodesic; an explicit expression for torsion takes a simple form of the axial vector current $\text{ψ}\text{γ}{}_5\text{γ}{}_{\mathrm{k}}\text{ψ}$.     

Measurement of antiproton lifetime using the ice storage ring

Antiprotons have been stored in the ICE Storage Ring and held for 85h with the help of stochastic cooling. We set a limit of at least 32 h for the antiproton lifetime (in its rest frame).