A HEURISTIC PATH-PLANNING METHOD FOR ENHANCING MACHINE-TOOL CONTOUR-FOLLOWING

Nomenclature ki integral action coefficient[s-1]kp speed proportional gain[s-1]kv position proportional gain[s-1]kf feed forward factor of the speed loop[%]M axis mass[kg]V speed[m/s]F driving effort[N]Rc radius of curvature[m]d distance to the apex[m]o lateral offset[m]εcontouring error[m]ωm lowest mechanical resonant frequency[s-1]ζdamping coefficient[-]r inertia ratio[-]μmembership function[-]αcorner angle[rad]x,y horizontal and vertical coordinates[m]?angle to the normal line[rad]1.I…     

An earlier origin for the Acheulian

The Acheulian is one of the first defined prehistoric techno-complexes and is characterized by shaped bifacial stone tools. It probably originated in Africa, spreading to Europe and Asia perhaps as early as ～1?million years (Myr) ago. The origin of the Acheulian is thought to have closely coincided with major changes in human brain evolution, allowing for further technological developments. Nonetheless, the emergence of the Acheulian remains unclear because well-dated sites older than 1.4?Myr ago are scarce. Here we report on the lithic assemblage and geological context for the Kokiselei 4 archaeological site from the Nachukui formation (West Turkana, Kenya) that bears characteristic early Acheulian tools and pushes the first appearance datum for this stone-age technology back to 1.76?Myr ago. Moreover, co-occurrence of Oldowan and Acheulian artefacts at the Kokiselei site complex indicates that the two technologies are not mutually exclusive time-successive components of an evolving cultural lineage, and suggests that the Acheulian was either imported from another location yet to be identified or originated from Oldowan hominins at this vicinity. In either case, the Acheulian did not accompany the first human dispersal from Africa despite being available at the time. This may indicate that multiple groups of hominins distinguished by separate stone-tool-making behaviours and dispersal strategies coexisted in Africa at 1.76?Myr ago.     

A prokaryotic proton-gated ion channel from the nicotinic acetylcholine receptor family

Ligand-gated ion channels (LGICs) mediate excitatory and inhibitory transmission in the nervous system. Among them, the pentameric or 'Cys-loop' receptors (pLGICs) compose a family that until recently was found in only eukaryotes. Yet a recent genome search identified putative homologues of these proteins in several bacterial species. Here we report the cloning, expression and functional identification of one of these putative homologues from the cyanobacterium Gloeobacter violaceus. It was expressed as a homo-oligomer in HEK 293 cells and Xenopus oocytes, generating a transmembrane cationic channel that is opened by extracellular protons and shows slow kinetics of activation, no desensitization and a single channel conductance of 8 pS. Electron microscopy and cross-linking experiments of the protein fused to the maltose-binding protein and expressed in Escherichia coli are consistent with a homo-pentameric organization. Sequence comparison shows that it possesses a compact structure, with the absence of the amino-terminal helix, the canonical disulphide bridge and the large cytoplasmic domain found in eukaryotic pLGICs. Therefore it embodies a minimal structure required for signal transduction. These data establish the prokaryotic origin of the family. Because Gloeobacter violaceus carries out photosynthesis and proton transport at the cytoplasmic membrane, this new proton-gated ion channel might contribute to adaptation to pH change.     

X-ray structure of a pentameric ligand-gated ion channel in an apparently open conformation

Pentameric ligand-gated ion channels from the Cys-loop family mediate fast chemo-electrical transduction, but the mechanisms of ion permeation and gating of these membrane proteins remain elusive. Here we present the X-ray structure at 2.9 A resolution of the bacterial Gloeobacter violaceus pentameric ligand-gated ion channel homologue (GLIC) at pH 4.6 in an apparently open conformation. This cationic channel is known to be permanently activated by protons. The structure is arranged as a funnel-shaped transmembrane pore widely open on the outer side and lined by hydrophobic residues. On the inner side, a 5 A constriction matches with rings of hydrophilic residues that are likely to contribute to the ionic selectivity. Structural comparison with ELIC, a bacterial homologue from Erwinia chrysanthemi solved in a presumed closed conformation, shows a wider pore where the narrow hydrophobic constriction found in ELIC is removed. Comparative analysis of GLIC and ELIC reveals, in concert, a rotation of each extracellular beta-sandwich domain as a rigid body, interface rearrangements, and a reorganization of the transmembrane domain, involving a tilt of the M2 and M3 alpha-helices away from the pore axis. These data are consistent with a model of pore opening based on both quaternary twist and tertiary deformation.     

Perpendicular switching of a single ferromagnetic layer induced by in-plane current injection

Modern computing technology is based on writing, storing and retrieving information encoded as magnetic bits. Although the giant magnetoresistance effect has improved the electrical read out of memory elements, magnetic writing remains the object of major research efforts. Despite several reports of methods to reverse the polarity of nanosized magnets by means of local electric fields and currents, the simple reversal of a high-coercivity, single-layer ferromagnet remains a challenge. Materials with large coercivity and perpendicular magnetic anisotropy represent the mainstay of data storage media, owing to their ability to retain a stable magnetization state over long periods of time and their amenability to miniaturization. However, the same anisotropy properties that make a material attractive for storage also make it hard to write to. Here we demonstrate switching of a perpendicularly magnetized cobalt dot driven by in-plane current injection at room temperature. Our device is composed of a thin cobalt layer with strong perpendicular anisotropy and Rashba interaction induced by asymmetric platinum and AlOx interface layers. The effective switching field is orthogonal to the direction of the magnetization and to the Rashba field. The symmetry of the switching field is consistent with the spin accumulation induced by the Rashba interaction and the spin-dependent mobility observed in non-magnetic semiconductors, as well as with the torque induced by the spin Hall effect in the platinum layer. Our measurements indicate that the switching efficiency increases with the magnetic anisotropy of the cobalt layer and the oxidation of the aluminium layer, which is uppermost, suggesting that the Rashba interaction has a key role in the reversal mechanism. To prove the potential of in-plane current switching for spintronic applications, we construct a reprogrammable magnetic switch that can be integrated into non-volatile memory and logic architectures. This device is simple, scalable and compatible with present-day magnetic recording technology.     

X-ray structures of general anaesthetics bound to a pentameric ligand-gated ion channel

General anaesthetics have enjoyed long and widespread use but their molecular mechanism of action remains poorly understood. There is good evidence that their principal targets are pentameric ligand-gated ion channels (pLGICs) such as inhibitory GABA(A) (γ-aminobutyric acid) receptors and excitatory nicotinic acetylcholine receptors, which are respectively potentiated and inhibited by general anaesthetics. The bacterial homologue from Gloeobacter violaceus (GLIC), whose X-ray structure was recently solved, is also sensitive to clinical concentrations of general anaesthetics. Here we describe the crystal structures of the complexes propofol/GLIC and desflurane/GLIC. These reveal a common general-anaesthetic binding site, which pre-exists in the apo-structure in the upper part of the transmembrane domain of each protomer. Both molecules establish van der Waals interactions with the protein; propofol binds at the entrance of the cavity whereas the smaller, more flexible, desflurane binds deeper inside. Mutations of some amino acids lining the binding site profoundly alter the ionic response of GLIC to protons, and affect its general-anaesthetic pharmacology. Molecular dynamics simulations, performed on the wild type (WT) and two GLIC mutants, highlight differences in mobility of propofol in its binding site and help to explain these effects. These data provide a novel structural framework for the design of general anaesthetics and of allosteric modulators of brain pLGICs.