Rates and equilibria at the acetylcholine receptor of electrophorus electroplaques. A study of neurally evoked postsynaptic currents and of voltage-jump relaxations

Kinetic measurements are employed to reconstruct the steady-state activation of acetylcholine [Ach] receptor channels in electrophorus electroplaques. Neurally evoked postsynaptic currents (PSCs) decay exponentially; at 15°C the rate constant, α, equals 1.2 ms^(-1) at 0 mV and decreases e-fold for every 86 mV as the membrane voltage is made more negative. Voltage-jump relaxations have been measured with bath-applied ACh, decamethonium, carbachol, or suberylcholine. We interpret the reciprocal relaxation time 1/τ as the sum of the rate constant α for channel closing and a first-order rate constant for channel opening. Where measureable, the opening rate increases linearly with [agonist] and does not vary with voltage. The voltage sensitivity of small steady-state conductances (e- fold for 86 mV) equals that of the closing rate α, confirming that the opening rate has little or no additional voltage sensitivity. Exposure to α-bungarotoxin irreversibly decreases the agonist-induced conductance but does not affect the relaxation kinetics. Tubocurarine reversibly reduces both the conductance and the opening rate. In the simultaneous presence of two agonist species, voltage-jump relaxations have at least two exponential components. The data are fit by a model in which (a) the channel opens as the receptor binds the second in a sequence of two agonist molecules, with a forward rate constant to 10^(7) to 2x10^(8) M^(-1)s^(-1); and (b) the channel then closes as either agonist molecule dissociates, with a voltage-dependent rate constant of 10^(2) to 3x10^(3)s^(-1)

Functional Stoichiometry at the Nicotinic Receptor. The Photon Cross Section for Phase 1 Corresponds to Two Bis-Q Molecules per Channel

These experiments examine changes in the agonist-induced conductance that occur when the agonist-receptor complex is perturbed. Voltage-clamped Electrophorus electroplaques are exposed to the photoisomerizable agonist trans-Bis-Q A 1-µs laser flash photoisomerizes some trans-Bis-Q molecules bound to receptors; because the cis configuration is not an agonist, receptor channels close within a few hundred microseconds. This effect is called phase 1. We compare (a) the fraction of channels that close during phase 1 with (b) the fraction of trans-Bis-Q molecules that undergo trans → cis photoisomerization. Parameter a is measured as the fractional diminution in voltage-clamp currents during phase 1. Parameter b is measured by changes in the optical spectra of Bis-Q solutions caused by flashes . At low flash intensities, a is twice b, which shows that the channel can be closed by photoisomerizing either of two bound agonist molecules. Conventional dose-response studies with trans-Bis-Q also give a Hill coefficient of two. As a partial control for changes in the photochemistry caused by binding of Bis-Q to receptors, spectral measurements are performed on the photoisomerizable agonist QBr, covalently bound to solubilized acetylcholine receptors from Torpedo. The bound and free agonist molecules have the same photoisomerization properties. These results verify the concept that the open state of the acetylcholine receptor channel is much more likely to be associated with the presence of two bound agonist molecules than with a single such molecule

Conductance increases produced by bath application of cholinergic agonists to Electrophorus electroplaques

When solutions containing agonists are applied to the innervated face of an Electrophorus electroplaque, the membrane's conductance increases. The agonist-induced conductance is increased at more negative membrane potentials. The "instantaneous" current-voltage curve for agonist-induced currents is linear and shows a reversal potential near zero mV; chord conductances, calculated on the basis of this reversal potential, change epsilon-fold for every 62-mV change in potential when the conductance is small. Conductance depends non- linearly on small agonist concentrations; at all potentials, the dose-response curve has a Hill coefficient of 1.45 for decamethonium (Deca) and 1.90 for carbamylcholine (Carb). With agonist concentrations greater than 10^(-4) M Carb or 10^(-5) M Deca, the conductance rises to a peak 0.5-1.5 min after introduction of agonist, then declines with time; this effect resembles the "desensitization" reported for myoneural junctions. Elapid alpha-toxin, tubocurarine, and desensitization reduce the conductance without changing the effects of potential; the apparent dissociation constant for tubocurarine is 2 X 10^(-7) M. By contrast, procaine effects a greater fractional inhibition of the conductance at high negative potentials

Study of aerodynamic technology for single-cruise-engine VSTOL fighter/attack aircraft, phase 1

A conceptual design and analysis on a single engine VSTOL fighter/attack aircraft is completed. The aircraft combines a NASA/deHavilland ejector with vectored thrust and is capable of accomplishing the mission and point performance of type Specification 169, and a flight demonstrator could be built with an existing F101/DFE engine. The aerodynamic, aero/propulsive, and propulsive uncertainties are identified, and a wind tunnel program is proposed to address those uncertainties associated with wing borne flight

The transmission of nosocomial pathogens in an intensive care unit: a space–time clustering and structural equation modelling approach

We investigated the incidence of cases of nosocomial pathogens and risk factors in an intensive treatment unit ward to determine if the number of cases is dependent on location of patients and the colonization/infection history of the ward. A clustering approach method was developed to investigate the patterns of spread of cases through time for five microorganisms [methicillin-resistant Staphylococcus aureus (MRSA), Acinetobacter spp., Klebsiella spp., Candida spp., and Pseudomonas aeruginosa] using hospital microbiological monitoring data and ward records of patient-bed use. Cases of colonization/infection by MRSA, Candida and Pseudomonas were clustered in beds and through time while cases of Klebsiella and Acinetobacter were not. We used structural equation modelling to analyse interacting risk factors and the potential pathways of transmission in the ward. Prior nurse contact with colonized/infected patients, mediated by the number of patient-bed movements, were important predictors for all cases, except for those of Pseudomonas. General health and invasive surgery were significant predictors of cases of Candida and Klebsiella. We suggest that isolation and bed movement as a strategy to manage MRSA infections is likely to impact upon the incidence of cases of other opportunist pathogen

Drag reduction obtained by modifying a standard truck

A standard two-axle truck with a box-shaped cargo compartment was tested to determine whether significant reductions in aerodynamic drag could be obtained by modifying the front of the cargo compartment. The coastdown method was used to determine the total drag of the baseline vehicle, which had a square-cornered cargo box, and of several modified configurations. Test velocities ranged from 56.3 to 94.6 kilometers per hour (35 to 60 miles per hour). At 88.5 kilometers per hour (55 miles per hour), the aerodynamic drag reductions obtained with the modified configurations ranged from 8 to 30 percent

A comparison of charcoal- and slag-based constructed wetlands for acid mine drainage remediation

Subsurface-flow constructed wetlands (CW) with charcoal- or slag-based bed matrices were investigated for their potential use in remediating acid mine drainage (AMD). A CW is effectively a reactor in which some components of the wastewater are broken down by the organisms occurring within the CW, whilst others may be degraded by physico-chemical processes or a combination thereof. Two 200 ℓ small-scale CWs were built at the University. Commercially available charcoal and <19 mm basic oxygen furnace (BOF) slag were used as the bed matrices and the units were planted with a variety of plants. The units were exposed to an artificial AMD. The results showed that the systems removed almost all soluble iron and more than 75% of the sulphate. Both CWs were able to increase the pH of the AMD.Keywords: AMD, charcoal, slag, constructed wetlands, remediatio

Cortical gray-matter thinning is associated with age-related improvements on executive function tasks

Across development children show marked improvement in their executive functions (EFs), including the ability to hold information in working memory and to deploy cognitive control, allowing them to ignore prepotent responses in favor of newly learned behaviors. How does the brain support these age-related improvements? Age-related cortical gray-matter thinning, thought to result from selective pruning of inefficient synaptic connections and increases in myelination, may support age-related improvements in EFs. Here we used structural MRI to measure cortical thickness. We investigate the association between cortical thickness in three cortical regions of interest (ROIs), and age-related changes in cognitive control and working memory in 5–10 year old children. We found significant associations between reductions in cortical thickness and age-related improvements in performance on both working memory and cognitive control tasks. Moreover, we observed a dissociation between ROIs typically thought to underlie changes in cognitive control (right Inferior Frontal gyrus and Anterior Cingulate cortex) and age-related improvements in cognitive control, and ROIs for working memory (superior parietal cortex), and age-related changes in a working memory task. These data add to our growing understanding of how structural maturation of the brain supports vast behavioral changes in executive functions observed across childhood