Functional role of high-affinity anandamide transport, as revealed by selective inhibition

Anandamide, an endogenous ligand for central cannabinoid receptors, is released from neurons on depolarization and rapidly inactivated. Anandamide inactivation is not completely understood, but it may occur by transport into cells or by enzymatic hydrolysis. The compound N-(4-hydroxyphenyl)arachidonylamide (AM404) was shown to inhibit high-affinity anandamide accumulation in rat neurons and astrocytes in vitro, an indication that this accumulation resulted from carrier-mediated transport. Although AM404 did not activate cannabinoid receptors or inhibit anandamide hydrolysis, it enhanced receptor-mediated anandamide responses in vitro and in vivo. The data indicate that carrier-mediated transport may be essential for termination of the biological effects of anandamide, and may represent a potential drug target.     

Magnet Safety Assessment for ITER

The ITER magnet system consists of structurally linked sets of toroidal (TF) and poloidal (PF) field coils, central solenoid (CS), and various support structures. The coils are superconducting, force flow Helium cooled with a Kapton-Glass-Epoxy multilayer insulation system. The stored magnetic energy is about 100GJ in the TF system and 20GJ in the PF-CS. Coils and structure are maintained at 4 K by enclosing them in a vacuum cryostat. The cryostat, comprising an outer envelope to the magnets, forms most of the second radioactivity confinement barrier. The inner primary barrier is formed by the vacuum vessel, its ports and their extensions. To keep the machine size within acceptable bounds, it is essential that the magnets are in close proximity to both of the nuclear confinement barriers. The objective of the magnet design is that, although local damage to one of the barriers may occur in very exceptional circumstances, large scale magnet structural or thermal failure leading to simultaneous breaching of both barriers is not credible. Magnet accidents fall into three categories: thermal (which includes arcing arising from insulation failure and local overheating due to discharge failure in the event of a superconductor quench), structural (which includes component mechanical failure arising from material inadequacies, design errors and exceptional force patterns arising from coil shorts or control failures), and fluid (Helium release due to cooling line failure). After a preliminary survey to select initial faults conceivable within the present design, these faults are systematically analyzed to provide an assessment of the damage potential. The results of this damage assessment together with an assessment of the reliability of the monitoring and protective systems, shows that the magnets can operate with the required safety condition.     

Glial development in the Drosophila CNS requires concomitant activation of glial and repression of neuronal differentiation genes

Two classes of glial cells are found in the embryonic Drosophila CNS, midline glial cells and lateral glial cells. Midline glial development is triggered by EGF-receptor signalling, whereas lateral glial development is controlled by the gcm gene. Subsequent glial cell differentiation depends partly on the pointed gene. Here we describe a novel component required for all CNS glia development. The tramtrack gene encodes two zinc-finger proteins, one of which, ttkp69, is expressed in all non-neuronal CNS cells. We show that ttkp69 is downstream of gcm and can repress neuronal differentiation. Double mutant analysis and coexpression experiments indicate that glial cell differentiation may depend on a dual process, requiring the activation of glial differentiation by pointed and the concomitant repression of neuronal development by tramtrack.     

Diagnostic value of fundus examination in familial adenomatous polyposis

BACKGROUND: Multiple, bilateral lesions of congenital hypertrophy of the retinal pigment epithelium (CHRPE) have been described in patients suffering from familial adenomatous polyposis (FAP) since 1980. This study aimed to determine a reliable diagnostic criterion, based on the size and number of retinal CHRPE lesions, allowing the screening of patient carriers of the gene responsible for FAP. METHODS: 32 control subjects and 144 patients belonging to 85 FAP families were studied, divided into 124 carriers of the genetic alteration and 20 non-carriers. RESULTS: In carriers of the deleted gene, multiple, bilateral retinal lesions were consistently observed. Lesion situation, size, shape, and degree of pigmentation were variable however. A positive criterion for FAP was defined as the presence of at least four lesions whatever their size, or at least two lesions one of which is large. This criterion showed a high sensitivity (0.68) and a maximal specificity (1). Within each family, the retinal phenotypic expression was homogeneous. CHRPE lesions were observed in two thirds of the FAP families and absent from the remaining third. CONCLUSION: By using this new positive diagnostic criterion, fundus examination allows early detection of those children carrying the gene responsible for FAP in families positive at ocular examination.     

A noncompetitive peptide inhibitor of the nicotinic acetylcholine receptor from Conus purpurascens venom

A paralytic peptide, psi-conotoxin Piiie has been purified and characterized from Conus purpurascens venom. Electrophysiological studies indicate that the peptide inhibits the nicotinic acetylcholine receptor (nAChR). However, the peptide does not block the binding of alpha-bungarotoxin, a competitive nAChR antagonist. Thus, psi-conotoxin Piiie appears to inhibit the receptor at a site other than the acetylcholine-binding site. As ascertained by sequence analysis, mass spectrometry, and chemical synthesis, the peptide has the following covalent structure: HOOCCLYGKCRRYOGCSSASCCQR* (O = 4-trans hydroxyproline; * indicates an amidated C-terminus). The disulfide connectivity of the toxin is unrelated to the alpha- or the alphaA-conotoxins, the Conus peptide families that are competitive inhibitors of the nAChR, but shows homology to the mu-conotoxins (which are Na+ channel blockers).     

Positive temperature dependence of the electron impact ionizationcoefficient in In0.53Ga0.47As/InP HBTs

Impact ionization is a major limiting factor to the maximum operating voltage of InGaAs-based, high-speed transistors. In this work, data on the positive temperature dependence of the electron impact ionization coefficient α_n in In_0.53Ga_0.47As at medium-low electric fields are reported for the first time. The increase of α_n with temperature is opposite to the behavior normally observed in most semiconductors. This anomalous behavior implies the onset of a positive feedback between power dissipation and avalanche generation which may adversely affect the power handling capability of In_0.53Ga _0.47As-based devices, and which should be taken into account in device thermal modeling. In the experimental procedure, based on the measurement of the multiplication factor M-1 in npn In_0.53Ga _0.47As/InP Heterojunction Bipolar Transistors (HBT), particular care has been taken in order to rule out possible spurious, temperature-dependent contributions to the measured multiplication current     

Evaluation of the tensile and fatigue behaviourof a powder metallurgy beryllium/aluminium alloy

The tensile and fatigue behaviour of a powder metallurgy beryllium/aluminium alloy produced by Brush Wellman (Albemet 562) is determined as a function of temperature. The material is shown to have very high stiffness/density compared with common structural materials and moderate strength up to 232°C. The mechanical properties of the material do not vary significantly as a function of orientation for the extruded plate evaluated in this study. The stiffness of the material can be readily explained using standard composite theory, where the material is treated as a beryllium particle-reinforced aluminium matrix composite. To explain the observed strength levels, a combination of microstructural-based dislocation strengthening mechanisms is proposed to act in combination with continuum mechanics strengthening based on load transfer. Failure analysis reveals that the aluminium regions of the material fail in a ductile dimple fashion, while the beryllium regions exhibit a more brittle cleavage type failure. Fatigue failure was found to initiate at inclusions present in the material, but is still very high relative to conventional aluminium alloys. This revised version was published online in November 2006 with corrections to the Cover Date.     

Application of neural networks and machine learning in networkdesign

Communication network design is becoming increasingly complex, involving making networks more usable, affordable, and reliable. To help with this, we have proposed an expert network designer (END) for configuring, modeling, simulating, and evaluating large structured computer networks, employing artificial intelligence, knowledge representation, and network simulation tools. We present a neural network/knowledge acquisition machine-learning approach to improve the END's efficiency in solving the network design problem and to extend its scope to acquire new networking technologies, learn new network design techniques, and update the specifications of existing technologies