Measurement of Electrophysiological Signals In Vitro Using High-Performance Organic Electrochemical Transistors

Biological environments use ions in charge transport for information transmission. The properties of mixed electronic and ionic conductivity in organic materials make them ideal candidates to transduce physiological information into electronically processable signals. A device proven to be highly successful in measuring such information is the organic electrochemical transistor (OECT). Previous electrophysiological measurements performed using OECTs show superior signal-to-noise ratios than electrodes at low frequencies. Subsequent development has significantly improved critical performance parameters such as transconductance and response time. Here, interdigitated-electrode OECTs are fabricated on flexible substrates, with one such state-of-the-art device achieving a peak transconductance of 139 mS with a 138 µs response time. The devices are implemented into an array with interconnects suitable for micro-electrocorticographic application and eight architecture variations are compared. The two best-performing arrays are subject to the full electrophysiological spectrum using prerecorded signals. With frequency filtering, kHz-scale frequencies with 10 µV-scale voltages are resolved. This is supported by a novel quantification of the noise, which compares the gate voltage input and drain current output. These results demonstrate that high-performance OECTs can resolve the full electrophysiological spectrum and suggest that superior signal-to-noise ratios could be achieved in high frequency measurements of multiunit activity.     

Periodic dynamics of coupled cell networks I: rigid patterns of synchrony and phase relations

It has recently been proved by Golubitsky and coworkers that in any network of coupled dynamical systems, the possible 'rigid' patterns of synchrony of hyperbolic equilibria are determined by purely combinatorial properties of the network, known as 'balanced equivalence relations'. A pattern is 'rigid' if it persists under small 'admissible' perturbations of the differential equation — ones that respect the network structure. We discuss a natural generalisation of these ideas to time-periodic states, and motivate two basic conjectures, the Rigid Synchrony Conjecture and the Rigid Phase Conjecture. These conjectures state that for rigid hyperbolic time-periodic patterns, cells with synchronous dynamics must have synchronous input cells, and cells with phase-related dynamics must have input cells that have the same phase relations. We provide evidence supporting the two conjectures, by proving them for a special class of periodic orbits, which we call 'tame', under strong assumptions on the network architecture and the symmetries of the periodic state. The discussion takes place in the formal setting of coupled cell networks. We prove that rigid patterns of synchrony are balanced, together with the analogous result for rigid patterns of phase relations. The assumption on the network architecture simplifies the geometry of admissible vector fields, while tameness rules out patterns with non-trivial local or multilocal symmetry. The main idea is to perturb an admissible vector field in a way that retains sufficient control over the associated perturbed periodic orbit. We present two techniques for constructing these perturbations, both using a general theorem on groupoid-symmetrisation of vector fields, which has independent interest. In particular we introduce a method of 'patching' that makes local changes to an admissible vector field. Having established these results for all-to-all coupled networks and tame periodic orbits we prove more general versions that require these assumptions only on a suitable quotient network. These conditions are weaker and encompass a larger class of networks and periodic orbits. We give an example to show that rigidity cannot be relaxed to hyperbolicity. We also prove, without any technical assumptions, that rigidly synchronous or phase-related cells must be input-isomorphic, a necessary precondition for the two conjectures to hold.     

d-Tubocurarine accentuates the burn-induced upregulation of nicotinic acetylcholine receptors at the muscle membrane

BACKGROUND: Increases in acetylcholine receptors (AChRs) at the muscle membrane, induced by burn injury, have been associated with a hyperkalemic response to succinylcholine and resistance to d-tubocurarine-like drugs. Muscle relaxants often are administered to burn-injured patients in the intensive care unit to facilitate mechanical ventilation. This study in rats tested whether continuous administration of d-tubocurarine in subparalytic doses exaggerates the upregulation of AChRs induced by burn trauma. Subparalytic doses were used to avoid the confounding effects of immobilization. METHODS: Three days after an approximate 50% body surface area burn or sham injury, the animals received an infusion of 3.03 +/- 0.05 micrograms/h of d-tubocurarine or equal volume of saline directly to the left gastrocnemius muscle via catheter connected to a subcutaneously implanted osmotic pump. After 7 days of d-tubocurarine or saline infusion, the AChRs were quantitated using 125I-alpha-bungarotoxin. The AChRs on the d-tubocurarine or saline-infused left gastrocnemius were compared to the contralateral gastrocnemius in the same group. The right or left gastrocnemius AChRs were compared to the ipsilateral muscles between groups. These intra- and intergroup comparisons allowed the delineation of the effects of catheter irritation, burns, or d-tubocurarine on AChRs. RESULTS: Daily examination of the withdrawal response to toe-pinch revealed no evidence of paralysis. Weight loss in the burn-injury animals receiving d-tubocurarine or saline was similar, confirming that the infusion of d-tubocurarine did not impair the mobility of the animals to move and feed. The plasma d-tubocurarine concentration after 7 days of infusion was 26.0 +/- 12 ng/ml (mean +/- SE). Regardless of burn or sham injury or of d-tubocurarine or saline infusion, the concentration of AChRs on the left was consistently greater than in the contralateral right gastrocnemius muscles within the same group, indicating that manipulation of the area alone can result in upregulation of AChRs. The AChRs in the right gastrocnemius of burn-injured animals were greater than those in the same muscle of sham-injured animals, regardless of saline (7.24 +/- 0.9 vs. 5.7 +/- 0.5 fmoles/mg protein, P = 0.06) or d-tubocurarine (7.3 +/- 0.4 vs. 5.7 +/- 0.5, P < 0.05) infusion to the burn-injury groups. AChRs in the left gastrocnemius of burn-injury animals receiving d-tubocurarine were significantly greater than those in burn- or sham-injury animals receiving saline (13.9 +/- 1.1 vs. 9.8 +/- 1.2 and 7.1 +/- 0.5 fmoles/mg protein, respectively, P < 0.05). CONCLUSIONS: Burn-induced upregulation of AChRs is accentuated by infusion of subparalytic doses of d-tubocurarine. Concomitant administration of d-tubocurarine to burn-injured patients may result in further exaggeration of the aberrant responses to neuromuscular relaxants.     

Comparative evaluation of platforms for parallel Ant Colony Optimization

The rapidly growing field of nature-inspired computing concerns the development and application of algorithms and methods based on biological or physical principles. This approach is particularly compelling for practitioners in high-performance computing, as natural algorithms are often inherently parallel in nature (for example, they may be based on a “swarm”-like model that uses a population of agents to optimize a function). Coupled with rising interest in nature-based algorithms is the growth in heterogenous computing; systems that use more than one kind of processor. We are therefore interested in the performance characteristics of nature-inspired algorithms on a number of different platforms. To this end, we present a new OpenCL-based implementation of the Ant Colony Optimization algorithm, and use it as the basis of extensive experimental tests. We benchmark the algorithm against existing implementations, on a wide variety of hardware platforms, and offer extensive analysis. This work provides rigorous foundations for future investigations of Ant Colony Optimization on high-performance platforms.     

The Inhibition of Geographical Information in Digital Humanities Scholarship

Information about place and location is an essential part ofresearch in the humanities. There are many ways that methodsand tools for structuring, visualizing and analysing space,spatial behaviour, and spatial relationships can benefit humanitiesresearch but the use of spatial information in digital scholarshipby humanists remains very limited. The developing role of thestudy of place and location through geographical informationsystems (GIS) and other digital tools is discussed briefly beforeexamining the factors that are inhibiting the use of spatialdata in our research. The influences of current research practiceand the attitudes of scholarly institutions in the humanitiesare examined. This article will explore some of the potentialresearch applications but, possibly more importantly; it willalso examine why that potential is being developed so slowlyand discuss a possible way forward for the community.     

An adaptive production control system utilizing agent technology

Agents are intelligent software objects capable of reasoning about, and interacting with, their environment. This paper presents conceptual and prototypical models of an adaptive production control system based on agent technology. In the system presented both workpieces and resources are represented by agents. Supervisory agents are introduced as the production load on the resources increases and removed as the load decreases. These supervisory agents serve to balance the production load across resources and maximize overall throughput. Simulation studies are presented demonstrating improvements in throughput, resource utilization, and work-in-process inventories over systems invariant to production load.     

A case study of optimising UG2 flotation performance. Part 1: Bench,pilot and plant scale factors which influence Cr2O3 entrainment in UG2 flotation

In the Platinum Group Minerals (PGM) industry, almost all UG2 deposits being currently developed are deep level and bankable feasibility studies must rely entirely on batch testwork of borecore samples. Since UG2 has a significant chromite (FeO·Cr₂O₃) content, minimising chromium oxide (Cr₂O₃) recovery into final concentrate has become a critical aspect of downstream smelting since % Cr₂O₃ in furnace feed has a practical upper limit of about 2.5%. In most cases concentrate is toll smelted but penalties are severe depending on chromite content. Together with PGMs, the characterisation of chromite floatability and prediction of recovery and concentrate grade in a production plant using bench-scale data is therefore a key component of UG2 ore analysis. The need to accurately predict chromite recovery and particularly to identify characteristics that indicate when % Cr₂O₃ in concentrate can be reduced has a significant impact on the project’s financials and subsequent plant design.The natural floatability of chromite is low and its passage into concentrate is almost entirely by entrainment in water carry-over into concentrate whereas PGMs are recovered by true flotation. Optimising flotation performance has to accommodate these two completely different flotation behaviours in an effort to reject chromite whilst at the same time maximise Platinum Group Minerals (PGM) recovery and grade.Incorporating extensive testwork conducted by Barrick Platinum South Africa and Northam and other plant data, the paper traces chromite, and to a lesser extent PGM, floatability in bench, pilot and plant scales and highlights that certain mechanisms of chromite entrainment are consistent irrespective of cell size and efficiency.     

Hydromorphological,hydraulic and ecological effects of restored wood: findings and reflections from an academic partnership approach

Large wood (re)introduction can deliver multiple benefits in river restoration, but there is a dearth of the detailed and longer‐term post‐project monitoring and evaluation required for improving best practice. We present findings from an academic partnership approach to post‐project evaluation, based on successive MSc research projects on restored large wood in the Loddon catchment, UK. Field and modelling data reveal: (i) key differences in large wood features between restored and natural reaches; (ii) increased hydraulic retention and changes to mesohabitats associated with large wood; (iii) differences in macroinvertebrate community composition around large wood but a lack of site‐level effects; (iv) interactions between macrophytes and large wood that may be specific to restored reaches; (v) a need for further field and modelling studies to inform the accurate representation of large wood in hydraulic models. Some key challenges in partnership working are identified to aid planning and effectiveness of future collaborations.     

Application of high-throughput computing in bioinformatics

We describe the challenges faced when developing a Linux/PC-based cluster to apply bioinformatics algorithms to the rapidly increasing raw genomics data available. The calculations, which take around two months to complete, result in a powerful resource that can be used for data mining--most obviously for the human genome. Our current infrastructure consists of a 1314 node cluster with 1734 processors supporting both production and research. This paper highlights the problems in achieving high data throughput with such systems and shows that raw computer power is only one component of a complex problem.