Identification of an opioid kappa receptor subtype-selective N-substituent for (+)-(3R,4R)-dimethyl-4-(3-hydroxyphenyl)piperidine

A three-component library of compounds was prepared in parallel using multiple simultaneous solution-phase synthetic methodology. The compounds were biased toward opioid receptor antagonist activity by incorporating (+)-(3R,4R)-dimethyl-4-(3-hydroxyphenyl)piperidine (a potent, nonselective opioid pure antagonist) as one of the monomers. The other two monomers, which included N-substituted or unsubstituted Boc-protected amino acids and a range of substituted aryl carboxylic acids, were selected to add chemical diversity. Screening of these compounds in competitive binding experiments with the kappa opioid receptor selective ligand [3H]U69,593 led to the discovery of a novel kappa opioid receptor selective ligand, N-?(2'S)-[3-(4-hydroxyphenyl)propanamido]-3'-methylbutyl?-(3R, 4R)-dimethyl-4-(3-hydroxyphenyl)piperidine (8, RTI-5989-29). Additional structure-activity relationship studies suggested that 8 possesses lipophilic and hydrogen-bonding sites that are important to its opioid receptor potency and selectivity. These sites appear to exist predominantly within the kappa receptor since the selectivity arises from a 530-fold loss of affinity of 8 for the mu receptor and an 18-fold increase in affinity for the kappa receptor relative to the mu-selective ligand, (+)-N-[trans-4-phenyl-2-butenyl]-(3R, 4R)-dimethyl-4-(3-hydroxyphenyl)piperidine (5a). The degree of selectivity observed in the radioligand binding experiments was not observed in the functional assay. According to its ability to inhibit agonist stimulated binding of [35S]GTPgammaS at all three opioid receptors, compound 8 behaves as a mu/kappa opioid receptor pure antagonist with negligible affinity for the delta receptor.     

The Rank-Width of Edge-Coloured Graphs

A C-coloured graph is a graph, that is possibly directed, where the edges are coloured with colours from the set C. Clique-width is a complexity measure for C-coloured graphs, for finite sets C. Rank-width is an equivalent complexity measure for undirected graphs and has good algorithmic and structural properties. It is in particular related to the vertex-minor relation. We discuss some possible extensions of the notion of rank-width to C-coloured graphs. There is not a unique natural notion of rank-width for C-coloured graphs. We define two notions of rank-width for them, both based on a coding of C-coloured graphs by ${\mathbb{F}}^{*}$ -graphs— $\mathbb {F}$ -coloured graphs where each edge has exactly one colour from $\mathbb{F}\setminus \{0\},\ \mathbb{F}$ a field—and named respectively $\mathbb{F}$ -rank-width and $\mathbb {F}$ -bi-rank-width. The two notions are equivalent to clique-width. We then present a notion of vertex-minor for $\mathbb{F}^{*}$ -graphs and prove that $\mathbb{F}^{*}$ -graphs of bounded $\mathbb{F}$ -rank-width are characterised by a list of $\mathbb{F}^{*}$ -graphs to exclude as vertex-minors (this list is finite if $\mathbb{F}$ is finite). An algorithm that decides in time O(n ³) whether an $\mathbb{F}^{*}$ -graph with n vertices has $\mathbb{F}$ -rank-width (resp. $\mathbb{F}$ -bi-rank-width) at most k, for fixed k and fixed finite field $\mathbb{F}$ , is also given. Graph operations to check MSOL-definable properties on $\mathbb{F}^{*}$ -graphs of bounded $\mathbb{F}$ -rank-width (resp. $\mathbb{F}$ -bi-rank-width) are presented. A specialisation of all these notions to graphs without edge colours is presented, which shows that our results generalise the ones in undirected graphs.     

Internet addiction: Meta-synthesis of qualitative research for the decade 1996–2006

Internet addiction is “an individual’s inability to control their Internet use, which in turn leads to feelings of distress and functional impairment of daily activities” [Shapira, N., Lessig, M., Goldsmith, T., Szabo, S., Lazoritz, M., Gold, M. et al. (2003). Problematic Internet use: Proposed classification and diagnostic criteria. Depression and Anxiety, 17(4), 207–216]. Previous research in this field has offered inconclusive data on whether Internet addiction can be classified as a disorder. This study provides an in-depth and comprehensive analysis of internet addiction through a meta-synthesis of qualitative studies on excessive Internet use published during the period of 1996–2006. Several constructs pertaining to the domain of Internet addiction have been identified and a theoretical model of Internet addiction has been proposed.     

Adaptive IPTV services based on a novel IP Multimedia Subsystem

Heterogeneous communication devices are emerging and changing the way of communication. Innovative multimedia applications are now accessible through these embedded systems. The 3GPP IP Multimedia Subsystem (IMS) provides a basic architecture framework for the Next Generation Network (NGN) supporting the convergence platform for service provisioning in heterogeneous networks. ETSI TISPAN standardization effort focuses on delivering IPTV services on such platform. Nevertheless, IPTV on IMS standardization suffers from a lack of efficient user-centric network management mechanisms as the end-user may consume IPTV service from different access networks, on different mobile devices, at anytime. User’s Perceived Quality of Service (PQoS) or Quality of Experience (QoE) of IPTV service may also suffer from wireless access network impairments. This paper introduces new functionalities in IPTV over IMS architecture which optimize satisfaction of the end-user and resource utilization of the operator’s networks. A context-sensitive User Profile (UP) model is used to deliver IPTV streams adapted to the user’s environment. In order to optimize the operator network usage, the impact of spatiotemporal dynamics of the video content on the deduced perceptual quality is considered. A Multimedia Content Management System (MCMS) is proposed to perform dynamic cross-layer adaptation of the IPTV stream based on PQoS measurements at the end-user side.     

The design and implementation of a session layer for delay-tolerant networks

The DTN architecture is based around sender-initiated unicast communication that is insufficient or inconvenient to meet the needs of many applications. To address these limitations, we define a DTN session layer and associated extensions to the DTN bundle protocol that more naturally support receiver-driven applications and multicast communication. Within a session, we provide mechanisms allowing applications to convey ordering relationships between successive transmissions that can be used by the network to help ensure a distributed application’s delivery ordering expectations are met. We also extend the bundle protocol’s expiration procedures to support more efficient network utilization by allowing in-network deletion of obsolete messages. We present the design rationale and describe our implementation of these mechanisms and discuss their advantages in meeting the needs of several popular types of applications.     

A method to select a successful interoperability solution through a simulation approach

Enterprise applications and software systems need to be interoperable in order to achieve seamless business across organizational boundaries and thus realize virtual networked organizations. Our proposition can be considered as an interoperability project selection approach and is based on three steps: (1) Modelling both collaborative business processes and potential related interoperability projects; (2) Evaluating the accessibility of each project regarding the current state of the organization; (3) Simulating each project and assessing the associated performance. These results are finally projected on a comparison matrix used as a decision support to select the most appropriate interoperability solution. An application case extracted from the French aerospace sector demonstrates the applicability and the benefits of the proposition.     

The effect of photo-oxidation on thermal and fire retardancy of polypropylene nanocomposites

Nanocomposites of polypropylene-graft-maleic anhydride/clay were prepared by melt blending in an extruder mixer. The nanoscale dispersion of the clay in the polymer was analysed by wide-angle X-ray diffraction (XRD) and transmission electron microscopy (TEM). The results of XRD and TEM showed that the nanocomposites obtained were a kind of intercalated-delaminated structures side by side with different dominant states, depending on the clay used and on the processing conditions. The consequences of photo-oxidation on the thermal stability and fire retardant properties of the nanocomposites were investigated using thermogravimetric analysis and cone calorimetry tests. It appeared that this degradation dramatically affected the important properties of the nanocomposites. A loss of thermal stability and fire retardant performance was observed. This was ascribed to scission reactions that occurred during the oxidative degradation prior to thermal and fire tests.     

Using pore space 3D geometrical modelling to simulate biological activity: Impact of soil structure

This study is the follow-up to a previous one devoted to soil pore space modelling. In the previous study, we proposed algorithms to represent soil pore space by means of optimal piecewise approximation using simple 3D geometrical primitives: balls, cylinders, cones, etc. In the present study, we use the ball-based piecewise approximation to simulate biological activity. The basic idea for modelling pore space consists in representing pore space using a minimal set of maximal balls (Delaunay spheres) recovering the shape skeleton. In this representation, each ball is considered as a maximal local cavity corresponding to the “intuitive” notion of a pore as described in the literature. The space segmentation induced by the network of balls (pores) is then used to spatialise biological dynamics. Organic matter and microbial decomposers are distributed within the balls (pores). A valuated graph representing the pore network, organic matter and microorganism distribution is then defined. Microbial soil organic matter decomposition is simulated by updating this valuated graph. The method has been implemented and tested on real data. As far as we know, this approach is the first one to formally link pore space geometry and biological dynamics. The long-term goal is to define geometrical typologies of pore space shape that can be attached to specific biological dynamic properties. This paper is a first attempt to achieve this goal.