A Chip for an Implantable Neural Stimulator

This paper describes a chip for a multichannel neural stimulator for functional electrical stimulation (FES). The purpose of FES is to restore muscular control in disabled patients. The chip performs all the signal processing required in an implanted neural stimulator. The power and digital data transmission to the stimulator passes through a 5 MHz inductive link. From the signals transmitted to the stimulator, the chip is able to generate charge-balanced current pulses with a controllable length up to 256 s and an amplitude up to 2 mA, for stimulation of nerve fibers. The quiescent current consumption of the chip is approx. 650 A at supply voltages of 6–12 V, and its size is 3.9×3.5 mm². It has 4 output channels for use in a multipolar cuff electrode.     

Selecting informative data for developing peptide-MHC binding predictors using a query by committee approach

Strategies for selecting informative data points for training prediction algorithms are important, particularly when data points are difficult and costly to obtain. A Query by Committee (QBC) training strategy for selecting new data points uses the disagreement between a committee of different algorithms to suggest new data points, which most rationally complement existing data, that is, they are the most informative data points. In order to evaluate this QBC approach on a real-world problem, we compared strategies for selecting new data points. We trained neural network algorithms to obtain methods to predict the binding affinity of peptides binding to the MHC class I molecule, HLA-A2. We show that the QBC strategy leads to a higher performance than a baseline strategy where new data points are selected at random from a pool of available data. Most peptides bind HLA-A2 with a low affinity, and as expected using a strategy of selecting peptides that are predicted to have high binding affinities also lead to more accurate predictors than the base line strategy. The QBC value is shown to correlate with the measured binding affinity. This demonstrates that the different predictors can easily learn if a peptide will fail to bind, but often conflict in predicting if a peptide binds. Using a carefully constructed computational setup, we demonstrate that selecting peptides with a high QBC performs better than low QBC peptides independently from binding affinity. When predictors are trained on a very limited set of data they cannot be expected to disagree in a meaningful way and we find a data limit below which the QBC strategy fails. Finally, it should be noted that data selection strategies similar to those used here might be of use in other settings in which generation of more data is a costly process.     

Upscaling and automation of electrophysiology: toward high throughput screening in ion channel drug discovery

Effective screening of large compound libraries in ion channel drug discovery requires the development of new electrophysiological techniques with substantially increased throughputs compared to the conventional patch clamp technique. Sophion Bioscience is aiming to meet this challenge by developing two lines of automated patch clamp products, a traditional pipette-based system called Apatchi-1, and a silicon chip-based system QPatch. The degree of automation spans from semi-automation (Apatchi-1) where a trained technician interacts with the system in a limited way, to a complete automation (QPatch 96) where the system works continuously and unattended until screening of a full compound library is completed. The performance of the systems range from medium to high throughputs.     

Fatigue-crack growth in Ti-6Al-4V-0.1Ru in air and seawater: Part II. crack path and microstructure

In Part I of this article, the influence of various testing parameters and environments on the fatigue-crack growth rates in samples of beta-annealed Ti-6Al-4V-0.1Ru (extra-low interstitials) ELI was reported.^[1] A design-of-experiments (DOE) approach was used to survey different combinations of variables, all expected to be important for dynamically loaded offshore oil and gas production risers, and to identify significant effects on the fatigue-crack propagation rate at a stress-intensity range of ΔK=17 MPa . The da/dN vs ΔK curves also were examined for the DOE and supplementary tests, and the results of the two approaches were compared. In this part of the study, the microstructural basis for the robust fatigue-crack growth resistance of beta-annealed Ti-6Al-4V-0.1Ru (ELI) samples was investigated with optical metallography and scanning electron microscopy (SEM). A gradual transition from structure-sensitive (microfacet formation) to structure-insensitive (striation formation) crack propagation centered at ΔK _trans ≅24 MPa , regardless of the combination of testing/environmental conditions examined; the absence of a sharp transition in the slope of the da/dN vs ΔK curves was, therefore, entirely consistent with the fracture-surface morphology. The size of the reversed cyclic plastic zone at the transition ΔK value correlated with the size of the lamella packets, but the number of cycles required to generate a striation ranged between one and ten, suggesting that the crack actively grew over only a portion of its front at any one instant. It is interesting to note that ΔK _trans was the same as the stress range where the da/dN curves at 0.2, 2, and 20 Hz (in seawater) converged to a single curve (refer to Part I of this article): at lower stress ranges, crack growth rates at 20 Hz were significantly higher than those at 0.2 and 2 Hz. The quantitative data showed that fatigue cracks propagated parallel to lamellae interfaces when the long axes of the lamellae made a relatively small angle (<30 deg) to the nominal crack-propagation direction. The crack cut directly across lamellae (i.e., perpendicular to their surfaces) when the long axes of the lamellae were nearly perpendicular to the nominal crack-propagation direction. If the lamellae long axes lay 45 deg to the crack-propagation direction, the crack deflected to run parallel or perpendicular to the lamellae. This behavior occurred regardless of the environment and loading conditions investigated. There was considerable variation in the amount that the cracks deviated from their nominal plane (i.e., the plane normal to the load axis and through the notch tip), with much greater deflections in the cold-rolled than in the parent material, but the angle of the macroscopic crack plane did not exceed 11 deg. Crack branching was observed both at the center and outer surfaces of the samples, regardless of ΔK or other parameters. The relationship between micro- and macrobranches was examined, and branching was more prominent below ΔK _trans, which separated the structure-sensitive and continuum-mode crack-propagation regimes. The relative amounts of micro- and microbranches are reported, and this branching may explain the large scatter in the measurements of the fatigue-crack growth rate often encountered in Ti-6Al-4V and its variants and points to the need for thorough characterization of crack paths, both midplane and surface, as part of the interpretation of da/dN vs ΔK data.     

Single tree species classification with a hypothetical multi-spectral satellite

The requirements for high resolution multi-spectral satellite images to be used in single tree species classification for forest inventories are investigated, especially with respect to spatial resolution, sensor noise and geo-registration. In the hypothetical setup, a 3D tree crown map is first obtained from very high resolution panchromatic aerial imagery and subsequently each crown is classified into one of a set of known tree species such that the difference between a model multi-spectral image generated from the 3D crown map and an acquired multi-spectral satellite image of the forested area is minimized. The investigation is conducted partly by generating synthetic data from a 3D crown map from a real mixed forest stand and partly on hypothetical high resolution multi-spectral satellite images obtained from very high resolution colour infrared aerial photographs, allowing different hypothetical spatial resolutions. Conclusions are that until a new generation of even higher resolution satellites becomes available, the most feasible source of remote sensing data for single tree classification will be aerial platforms.     

Relaxing PWQ Lyapunov stability criteria for PWA systems

The note addresses the calculation of piecewise quadratic (PWQ) Lyapunov functions for PWA (piecewise affine) systems. New LMI relaxations are proposed. These relaxations have been found to be effective in cases where the traditional relaxations fail.     

A patchy approximation of explicit model predictive control

The explicit solution of multi-parametric optimisation problems (MPOP) has been used to construct an off-line solution to relatively small- and medium-sized constrained control problems. The control design principles are based on receding horizon optimisation and generally use linear prediction models for the system dynamics. In this context, it can be shown that the optimal control law is a piecewise linear (PWL) state feedback defined over polytopic cells of the state space. However, as the complexity of the related optimisation problems increases, the memory footprint and implementation of such explicit optimal solution may be burdensome for the available hardware, principally due to the high number of polytopic cells in the state-space partition. In this article we provide a solution to this problem by proposing a patchy PWL feedback control law, which intend to approximate the optimal control law. The construction is based on the linear interpolation of the exact solution at the vertices of a feasible set and the solution of an unconstrained linear quadratic regulator (LQR) problem. With a hybrid patchy control implementation, we show that closed-loop stability is preserved in the presence of additive measurement noise despite the existence of discontinuities at the switch between the overlapping regions in the state-space partition.     

Measurement of CH4-concentration in HMDSO-containing process plasmas by quantum cascade laser absorption spectroscopy

For thin film deposition or plasma etching often organic precursors are used in the process plasma and related transient species are formed. In general it is not possible to measure the converted quantity of these precursors directly. In the present work we have used a special laser absorption spectroscopy to investigate characteristic molecular lines in the plasma to determine the concentration of stable organic molecules. Quantum cascade laser absorption spectroscopy (QCLAS) is a rather new technique for the precise measurement of absolute molecule concentrations. QCL’s can be operated at room temperature. They emit light within the mid infrared and have similar spectroscopic characteristics to Tunable Diode Lasers (TDL). The commercially available system Q-MACS (Quantum Cascade Laser Measurement and Control System) offers a solid platform for the measurement of absolute molecule concentrations in plasmas and gas mixtures. The used Q-MACS is due to its laser characteristics particularly well suitable for determination of the concentrations of acetylene and methane. Molecular concentrations of methane were measured in hexamethyldisiloxane (HMDSO) containing plasmas, too. The methane concentration was found to depend on rf power and HMDSO flow.     

An investigation of governance frameworks for public projects in Norway and the UK

This paper describes four case studies which formed a key part of an investigation into public investment project governance frameworks in Norway and the UK. The studies looked at how the embedded governance principles worked out in practice, how they affected PM, and how consistent their effects were with their aims. Conclusion is made about the actual effects of the frameworks, and various areas for improvement or further study are highlighted.     

The total quasi-steady-state approximation for complex enzyme reactions

Biochemistry in general and enzyme kinetics in particular have been heavily influenced by the model of biochemical reactions known as Michaelis–Menten kinetics. Assuming that the complex concentration is approximately constant after a short transient phase leads to the usual Michaelis–Menten (MM) approximation (or standard quasi-steady-state approximation (sQSSA)), which is valid when the enzyme concentration is sufficiently small. This condition is usually fulfilled for in vitro experiments, but often breaks down in vivo. The total QSSA (tQSSA), which is valid for a broader range of parameters covering both high and low enzyme concentrations, has been introduced in the last two decades. We extend the tQSSA to more complex reaction schemes, like fully competitive reactions, double phosphorylation, Goldbeter–Koshland switch and we show that for a very large range of parameters our tQSSA provides excellent fitting to the solutions of the full system, better than the sQSSA and the single reaction tQSSA. Finally, we discuss the need for a correct model formulation when doing “reverse engineering”, which aims at finding unknown parameters by fitting the model to experimentally obtained data. We show that the estimated parameters are much closer to the real values when using the tQSSA rather than the sQSSA, which overestimates the parameter values greatly.