FMP study of pilot workload. Qualification of workload via instrument scan

Various methods of measuring a pilot's mental workload are discussed. Scanning the various flight instruments with good scan pattern and other verbal tasks during instrument landings is given special attention for measuring pilot workload

Intracellular protons control the affinity of skeletal muscle ATP-sensitive K+ channels for potassium-channel-openers

AbstractLevcromakalim, a potential antihypertensive agent, is known to activate potassium channels dependent on intracellular ATP (K-ATP channels). In inside-out patches excised from frog skeletal muscle, levcromakalim or a related compound, SR 47063, caused a strong and persistent activation of K-ATP channels at a cytoplasmic pH of 7.1. However, at pH 6, these activators could no longer affect the K-ATP currents. Conversely, in the continuous presence of activator, lowering pH from 7.1 to 6 returned channel activity to its level in pH 6 alone. After wash-out of the activator, recovery from activation took minutes at pH 7.1 but only seconds at pH 6, thus ruling out an effect of protons on the activators in solution. These experiments suggest that K-channel-activators are unable to bind to their receptor when it is protonated, and more generally, they provide evidence at the microscopic level for proton-induced allosteric modulation of drug-receptor interaction

Visual scanning behavior and pilot workload

Sophisticated man machine interaction often requires the human operator to perform a stereotyped scan of various instruments in order to monitor and/or control a system. For situations in which this type of stereotyped behavior exists, such as certain phases of instrument flight, scan pattern was shown to be altered by the imposition of simultaneous verbal tasks. A study designed to examine the relationship between pilot visual scan of instruments and mental workload is described. It was found that a verbal loading task of varying difficulty causes pilots to stare at the primary instrument as the difficulty increases and to shed looks at instruments of less importance. The verbal loading task also affected the rank ordering of scanning sequences. By examining the behavior of pilots with widely varying skill levels, it was suggested that these effects occur most strongly at lower skill levels and are less apparent at high skill levels. A graphical interpretation of the hypothetical relationship between skill, workload, and performance is introduced and modelling results are presented to support this interpretation

Entropy, instrument scan and pilot workload

Correlation and information theory which analyze the relationships between mental loading and visual scanpath of aircraft pilots are described. The relationship between skill, performance, mental workload, and visual scanning behavior are investigated. The experimental method required pilots to maintain a general aviation flight simulator on a straight and level, constant sensitivity, Instrument Landing System (ILS) course with a low level of turbulence. An additional periodic verbal task whose difficulty increased with frequency was used to increment the subject's mental workload. The subject's looppoint on the instrument panel during each ten minute run was computed via a TV oculometer and stored. Several pilots ranging in skill from novices to test pilots took part in the experiment. Analysis of the periodicity of the subject's instrument scan was accomplished by means of correlation techniques. For skilled pilots, the autocorrelation of instrument/dwell times sequences showed the same periodicity as the verbal task. The ability to multiplex simultaneous tasks increases with skill. Thus autocorrelation provides a way of evaluating the operator's skill level

Hourglass SiO2 coating increases the performance of planar patch-clamp.

International audienceObtaining high-throughput electrophysiological recordings is an ongoing challenge in ion channel biophysics and drug discovery. One particular area of development is the replacement of glass pipettes with planar devices in order to increase throughput. However, successful patch-clamp recordings depend on a surface coating which ideally should promote and stabilize giga-seal formation. Here, we present data supporting the use of a structured SiO(2) coating to improve the ability of cells to form a "seal" with a planar patch-clamp substrate. The method is based on a correlation study taking into account structure and size of the pores, surface roughness and chip capacitance. The influence of these parameters on the quality of the seal was assessed. Plasma-enhanced chemical vapour deposition (PECVD) of SiO(2) led to an hourglass structure of the pore and a tighter seal than that offered by a flat, thermal SiO(2) surface. The performance of PECVD chips was validated by recording recombinant potassium channels, BK(Ca), expressed in stable HEK-293 cell lines and in inducible CHO cell lines and low conductance IRK1, and endogenous cationic currents from CHO cells. This multiparametric investigation led to the production of improved chips for planar patch-clamp applications which allow electrophysiological recordings from a wide range of cell lines

Elevations of intracellular calcium reflect normal voltage-dependent behavior, and not constitutive activity, of voltage-dependent calcium channels in gastrointestinal and vascular smooth muscle

In smooth muscle, the gating of dihydropyridine-sensitive Ca2+ channels may either be stochastic and voltage dependent or coordinated among channels and constitutively active. Each form of gating has been proposed to be largely responsible for Ca2+ influx and determining the bulk average cytoplasmic Ca2+ concentration. Here, the contribution of voltage-dependent and constitutively active channel behavior to Ca2+ signaling has been studied in voltage-clamped single vascular and gastrointestinal smooth muscle cells using wide-field epifluorescence with near simultaneous total internal reflection fluorescence microscopy. Depolarization (−70 to +10 mV) activated a dihydropyridine-sensitive voltage-dependent Ca2+ current (ICa) and evoked a rise in [Ca2+] in each of the subplasma membrane space and bulk cytoplasm. In various regions of the bulk cytoplasm the [Ca2+] increase ([Ca2+]c) was approximately uniform, whereas that of the subplasma membrane space ([Ca2+]PM) had a wide range of amplitudes and time courses. The variations that occurred in the subplasma membrane space presumably reflected an uneven distribution of active Ca2+ channels (clusters) across the sarcolemma, and their activation appeared consistent with normal voltage-dependent behavior. Indeed, in the present study, dihydropyridine-sensitive Ca2+ channels were not normally constitutively active. The repetitive localized [Ca2+]PM rises (“persistent Ca2+ sparklets”) that characterize constitutively active channels were observed rarely (2 of 306 cells). Neither did dihydropyridine-sensitive constitutively active Ca2+ channels regulate the bulk average [Ca2+]c. A dihydropyridine blocker of Ca2+ channels, nimodipine, which blocked ICa and accompanying [Ca2+]c rise, reduced neither the resting bulk average [Ca2+]c (at −70 mV) nor the rise in [Ca2+]c, which accompanied an increased electrochemical driving force on the ion by hyperpolarization (−130 mV). Activation of protein kinase C with indolactam-V did not induce constitutive channel activity. Thus, although voltage-dependent Ca2+ channels appear clustered in certain regions of the plasma membrane, constitutive activity is unlikely to play a major role in [Ca2+]c regulation. The stochastic, voltage-dependent activity of the channel provides the major mechanism to generate rises in [Ca2+]

Optical Control of Metabotropic Glutamate Receptors

G-protein coupled receptors (GPCRs), the largest family of membrane signaling proteins, respond to neurotransmitters, hormones and small environmental molecules. The neuronal function of many GPCRs has been difficult to resolve because of an inability to gate them with subtype-specificity, spatial precision, speed and reversibility. To address this, we developed an approach for opto-chemical engineering native GPCRs. We applied this to the metabotropic glutamate receptors (mGluRs) to generate light-agonized and light-antagonized “LimGluRs”. The light-agonized “LimGluR2”, on which we focused, is fast, bistable, and supports multiple rounds of on/off switching. Light gates two of the primary neuronal functions of mGluR2: suppression of excitability and inhibition of neurotransmitter release. The light-antagonized “LimGluR2block” can be used to manipulate negative feedback of synaptically released glutamate on transmitter release. We generalize the optical control to two additional family members: mGluR3 and 6. The system works in rodent brain slice and in zebrafish in vivo, where we find that mGluR2 modulates the threshold for escape behavior. These light-gated mGluRs pave the way for determining the roles of mGluRs in synaptic plasticity, memory and disease

eeFit: a Microsoft Excel-embedded program for interactive analysis and fitting of experimental dose–response data

International audienceWe present here a software program dedicated to the fitting of experimental dose-response data, which integrates seamlessly with Excel and allows curve fitting plots and results to reside alongside data within Excel spreadsheets. The program, named eeFit, for Excel-Embedded Fitting software, requires no advanced knowledge of Excel or non-linear least-squares fitting. Any experimental data present in an Excel file, such as dose-effect data obtained with membrane receptor or ion channel ligands, can be graphed and fitted interactively with standard Hill models for activation or inhibition, or with more complex models for biphasic effects resulting from combinations of activation and inhibition. When benchmarked against the commercial program Origin, eeFit yielded equivalent or better results, in terms of accuracy and convergence, and proved much easier to learn and use