Concomitant polymorphism of an antiferromagnetically coupled dicopper(II,II) complex with single strand helical assembly: synthesis, structure, DSC, magnetic and heterogeneous catalytic studies

Two concomitant polymorphic coordination complexes (dark blue - I and black - II) with the formula (Cu2C44H60N4O4) have been synthesized and characterized crystallographically. Magnetic measurements show the presence of a strong antiferromagnetic interaction and the 2J value corresponds extremely well to the theoretically calculated one, indicating the fact that it follows nicely the magneto-structural relationship. Immobilization of the copper(II) complex I on a 2D-hexagonal mesoporous silica showed good catalytic efficiency in the liquid phase partial oxidation of olefins in the presence of TBHP as an oxidant. (C) 2009 Elsevier Ltd. All rights reserved.

A diphenoxo bridged antiferromagnetically coupled dimer of copper(II) having bridging methanol

A dinuclear copper(II) complex, (mu2-MeOH)bis(mu(2)-phenoxide)dicopper complex with N-(3-aminopropyl)salicylaidimine, has been synthesised and characterised by X-ray structure determination. Variable temperature magnetic susceptibility measurement shows that it is strongly antiferromagnetically coupled. (C) 2003 Elsevier Science B.V. All rights reserved.

Peptide inhibitors of G protein-coupled receptor kinases

G protein-coupled receptor kinases (GRKs) are regulatory enzymes involved in the modulation of seven-transmembrane-helix receptors. In order to develop specific inhibitors for these kinases, we synthesized and investigated peptide inhibitors derived from the sequence of the first intracellular loop of the beta(2)-adrenergic receptor. Introduction of changes in the sequence and truncation of N- and C-terminal amino acids increased the inhibitory potency by a factor of 40. These inhibitors not only inhibited the prototypical GRK2 but also GRK3 and GRK5. In contrast there was no inhibition of protein kinase C and protein kinase A even at the highest concentration tested. The peptide with the sequence AKFERLQTVTNYFITSE inhibited GRK2 with an IC50 of 0.6 mu M, GRK3 with 2.6 mu M and GRK5 with 1.6 mu M. The peptide inhibitors were non-competitive for receptor and ATP. These findings demonstrate that specific peptides can inhibit GRKs in the submicromolar range and suggest that a further decrease in size is possible without losing the inhibitory potency. (c) 2005 Published by Elsevier Inc.

Agonist binding, agonist affinity and agonist efficacy at G protein-coupled receptors

Measurements of affinity and efficacy are fundamental for work on agonists both in drug discovery and in basic studies on receptors. In this review I wish to consider methods for measuring affinity and efficacy at G protein coupled receptors (GPCRs). Agonist affinity may be estimated in terms of the dissociation constant for agonist binding to a receptor using ligand binding or functional assays. It has, however, been suggested that measurements of affinity are always contaminated by efficacy so that it is impossible to separate the two parameters. Here I show that for many GPCRs, if receptor/G protein coupling is suppressed, experimental measurements of agonist affinity using ligand binding (K-obs) provide quite accurate measures of the agonist microscopic dissociation constant (K-A). Also in pharmacological functional studies, good estimates of agonist dissociation constants are possible. Efficacy can be quantitated in several ways based on functional data ( maximal effect of the agonist (E-max), ratio of agonist dissociation constant to concentration of agonist giving half maximal effect in functional assay ( K-obs/ EC50), a combined parameter EmaxKobs/EC50). Here I show that EmaxKobs/EC50 provides the best assessment of efficacy for a range of agonists across the full range of efficacy for full to partial agonists. Considerable evidence now suggests that ligand efficacy may be dependent on the pathway used to assess it. The efficacy of a ligand may, therefore, be multidimensional. It is still, however, necessary to have accurate measures of efficacy in different pathways.

An RNA molecule that specifically inhibits G-protein-coupled receptor kinase 2 in vitro

G-protein-coupled receptors are desensitized by a two-step process. In a first step, G-protein-coupled receptor kinases (GRKs) phosphorylate agonist-activated receptors that subsequently bind to a second class of proteins, the arrestins. GRKs can be classified into three subfamilies, which have been implicated in various diseases. The physiological role(s) of GRKs have been difficult to study as selective inhibitors are not available. We have used SELEX (systematic evolution of ligands by exponential enrichment) to develop RNA aptamers that potently and selectively inhibit GRK2. This process has yielded an aptamer, C13, which bound to GRK2 with a high affinity and inhibited GRK2-catalyzed rhodopsin phosphorylation with an IC50 of 4.1 nM. Phosphorylation of rhodopsin catalyzed by GRK5 was also inhibited, albeit with 20-fold lower potency (IC50 of 79 nM). Furthermore, C13 reveals significant specificity, since almost no inhibitory activity was detectable testing it against a panel of 14 other kinases. The aptamer is two orders of magnitude more potent than the best GRK2 inhibitors described previously and shows high selectivity for the GRK family of protein kinases.

Closely coupled behaviour in networked robot systems

Multiple cooperating robot systems may be required to take up a closely coupled configuration in order to perform a task. An example is extended baseline stereo (EBS), requiring that two robots must establish and maintain for a certain period of time a constrained kinematic relationship to each other. In this paper we report on the development of a networked robotics framework for modular, distributed robot systems that supports the creation of such configurations. The framework incorporates a query mechanism to locate modules distributed across the two robot systems. The work presented in this paper introduces special mechanisms to model the kinematic constraint and its instantiation. The EBS configuration is used as a case study and experimental implementation to demonstrate the approach.

U.K. HiGEM: Simulations of desert dust and biomass burning aerosols with a high-resolution atmospheric GCM

The atmospheric component of the United Kingdom’s new High-resolution Global Environmental Model (HiGEM) has been run with interactive aerosol schemes that include biomass burning and mineral dust. Dust emission, transport, and deposition are parameterized within the model using six particle size divisions, which are treated independently. The biomass is modeled in three nonindependent modes, and emissions are prescribed from an external dataset. The model is shown to produce realistic horizontal and vertical distributions of these aerosols for each season when compared with available satellite- and ground-based observations and with other models. Combined aerosol optical depths off the coast of North Africa exceed 0.5 both in boreal winter, when biomass is the main contributor, and also in summer, when the dust dominates. The model is capable of resolving smaller-scale features, such as dust storms emanating from the Bode´ le´ and Saharan regions of North Africa and the wintertime Bode´ le´ low-level jet. This is illustrated by February and July case studies, in which the diurnal cycles of model variables in relation to dust emission and transport are examined. The top-of-atmosphere annual mean radiative forcing of the dust is calculated and found to be globally quite small but locally very large, exceeding 20 W m22 over the Sahara, where inclusion of dust aerosol is shown to improve the model radiative balance. This work extends previous aerosol studies by combining complexity with increased global resolution and represents a step toward the next generation of models to investigate aerosol–climate interactions. 1. Introduction Accurate modeling of mineral dust is known to be important because of its radiative impact in both numerical weather prediction models (Milton et al. 2008; Haywood et

Coupled chemistry climate model simulations of stratospheric temperatures and their trends for the recent past

Temperature results from multi-decadal simulations of coupled chemistry climate models for the recent past are analyzed using multi-linear regression including a trend, solar cycle, lower stratospheric tropical wind, and volcanic aerosol terms. The climatology of the models for recent years is in good agreement with observations for the troposphere but the model results diverge from each other and from observations in the stratosphere. Overall, the models agree better with observations than in previous assessments, primarily because of corrections in the observed temperatures. The annually averaged global and polar temperature trends simulated by the models are generally in agreement with revised satellite observations and radiosonde data over much of their altitude range. In the global average, the model trends underpredict the radiosonde data slightly at the top of the observed range. Over the Antarctic some models underpredict the temperature trend in the lower stratosphere, while others overpredict the trends

Changes of interannual NAO variability in response to greenhouse gases forcing

Observations show that there was change in interannual North Atlantic Oscillation (NAO) variability in the mid-1970s. This change was characterized by an eastward shift of the NAO action centres, a poleward shift of zonal wind anomalies and a downstream extension of climate anomalies associated with the NAO. The NAO interannual variability for the period after the mid-1970s has an annular mode structure that penetrates deeply into the stratosphere, indicating a strengthened relationship between the NAO and the Arctic Oscillation (AO) and strengthened stratosphere-troposphere coupling. In this study we have investigated possible causes of these changes in the NAO by carrying out experiments with an atmospheric GCM. The model is forced either by doubling CO2, or increasing sea surface temperatures (SST), or both. In the case of SST forcing the SST anomaly is derived from a coupled model simulation forced by increasing CO2. Results indicate that SST and CO2 change both force a poleward and eastward shift in the pattern of interannual NAO variability and the associated poleward shift of zonal wind anomalies, similar to the observations. The effect of SST change can be understood in terms of mean changes in the troposphere. The direct effect of CO2 change, in contrast, can not be understood in terms of mean changes in the troposphere. However, there is a significant response in the stratosphere, characterized by a strengthened climatological polar vortex with strongly enhanced interannual variability. In this case, the NAO interannual variability has a strong link with the variability over the North Pacific, as in the annular AO pattern, and is also strongly related to the stratospheric vortex, indicating strengthened stratosphere-troposphere coupling. The similarity of changes in many characteristics of NAO interannual variability between the model response to doubling CO2 and those in observations in the mid-1970s implies that the increase of greenhouse gas concentration in the atmosphere, and the resulting changes in the stratosphere, might have played an important role in the multidecadal change of interannual NAO variability and its associated climate anomalies during the late twentieth century. The weak change in mean westerlies in the troposphere in response to CO2 change implies that enhanced and eastward extended mid-latitude westerlies in the troposphere might not be a necessary condition for the poleward and eastward shift of the NAO action centres in the mid-1970s.

The impact of the state of the troposphere on the response to stratospheric heating in a simplified GCM

Previous studies have made use of simplified general circulation models (sGCMs) to investigate the atmospheric response to various forcings. In particular, several studies have investigated the tropospheric response to changes in stratospheric temperature. This is potentially relevant for many climate forcings. Here the impact of changing the tropospheric climatology on the modeled response to perturbations in stratospheric temperature is investigated by the introduction of topography into the model and altering the tropospheric jet structure. The results highlight the need for very long integrations so as to determine accurately the magnitude of response. It is found that introducing topography into the model and thus removing the zonally symmetric nature of the model’s boundary conditions reduces the magnitude of response to stratospheric heating. However, this reduction is of comparable size to the variability in the magnitude of response between different ensemble members of the same 5000-day experiment. Investigations into the impact of varying tropospheric jet structure reveal a trend with lower-latitude/narrower jets having a much larger magnitude response to stratospheric heating than higher-latitude/wider jets. The jet structures that respond more strongly to stratospheric heating also exhibit longer time scale variability in their control run simulations, consistent with the idea that a feedback between the eddies and the mean flow is both responsible for the persistence of the control run variability and important in producing the tropospheric response to stratospheric temperature perturbations.