Subsecond adsorption and desorption of dopamine at carbon-fiber microelectrodes

High-repetition fast-scan cyclic voltammetry and chronoamperometry were used to quantify and characterize the kinetics of dopamine and dopamine-o-quinone adsorption and desorption at carbon-fiber microelectrodes. A flow injection analysis system was used for the precise introduction and removal of a bolus of electroactive substance on a sub-second time scale to the disk-shaped surface of a microelectrode that was fabricated from a single carbon fiber (Thornel type T650 or P55). Pretreatment of the electrode surfaces consisted of soaking them in purified isopropyl alcohol for a minimum of 10 min, which resulted in S/N increasing by 200-400% for dopamine above that for those that were soaked in reagent grade solvent. Because of adsorption, high scan rates (2,000 V/s) are shown to exhibit equivalent S/N ratios as compared to slower, more traditional scan rates. In addition, the steady-state response to a concentration bolus is shown to occur more rapidly when cyclic voltammetric scans are repeated at short intervals (4 ms). The new methodologies allow for more accurate determinations of the kinetics of neurotransmitter release events (10-500 ms) in biological systems. Brain slice and in vivo experiments using T650 cylinder microelectrodes show that voltammetrically measured uptake kinetics in the caudate are faster using 2,000 V/s and 240 Hz measurements, as compared to 300 V/s and 10 Hz.     

FINITE ELEMENT SIMULATION OF PHASE CHANGE USING CAPACITANCE METHODS

Two capacitance methods for finite element simulation of phase change problems are introduced. One is the “accelerated effective capacity method,” which is derived from Poirier and Salcudean's effective capacity method, and the other is the “exact apparent capacity method,” which is derived from the traditional apparent capacity method. Both of these new methods are developed by allowing the width of the “musky range” in the original methods to approach zero in a limiting process. The new methods are easier to implement in existing heat conduction codes than are most other fixed-grid methods. The methods are tested on one- and two-dimensional Stefan problems that have analytical solutions. It is found that the new methods are superior to the apparent capacity method, and their performance is comparable to that of the original effective capacity method and the enthalpy method for the test cases considered.     

A model for the packing of cells

An integrated course in Preventive and Community Medicine was introduced at the Christchurch Clinical School, New Zealand in 1974. Details of the fourth and fifth clinical years as well as the elective studies in the trainee intern (sixth) year are presented. The implications of the topic studies, rotating attachments, preventive medical examinations, preventive medical ward rounds, problem-orientated record studies, simulated disabilities and Clinico-Pathological Conferences are discussed. Some preliminary conclusions are drawn from the evaluation of this course.     

Advanced experimental and computational tools for robust evaluation of on-chip interconnect reliability

Two technologies are introduced that, together, provide a platform for robust evaluation of interconnect reliability. One is the DISMAP technology, which provides plots of the displacement and strain fields of cross-sectioned interconnect structures under various loading conditions. Measurements provided by DISMAP reveal how multilevel-interconnect structures interact structurally, for example what type of strain fields exist during thermal cycling. A complimentary technology, known as probabilistic analysis, is also described and applied using the NESSUS software. Probabilistic analysis combines statistical uncertainty with physics-based models to predict the probability of failure and also to reveal the relative importance of the various uncertainties associated with interconnect manufacturing. By comparing the predictions of physical models to DISMAP measurements, the validity of those models are evaluated.     

Advances in physically based erosion simulators for CMP

Advances in two types of chemical-mechanical planarization (CMP) erosion simulators are reported in the context of a CMP modeling overview. One advance is a physically based erosion simulation platform that is capable of simulating the complete erosion of multiple oxide features. The platform separates the erosion model from the stress model, making it easy to use and versatile. Another advance is the development of a hybrid approach to erosion modeling that mixes generic physics with phenomenological understanding. The hybrid simulator is capable of accurate three-dimensional erosion simulation across large patterns, a capability that will eventually lead to die-wide CMP simulation.     

Regulation of the rate and extent of phospholipase C beta 2 effector activation by the beta gamma subunits of heterotrimeric G proteins

The activity of mammalian phosphoinositide-specific phospholipase C beta 2 (PLC-beta 2) is regulated by the alpha q family of G proteins and by beta gamma subunits. We measured the affinity between the laterally associating PLC-beta 2 and G beta gamma on membrane surfaces by fluorescence resonance energy transfer. Using a simple model, we translated this apparent affinity to a bulk or three-dimensional equilibrium constant (Kd) and obtained a value of 3.2 microM. We confirmed this Kd by separately measuring the on and off (kf and kr) rate constants. The kf was slower than a diffusion-limited value, suggesting that conformational changes occur when the two proteins interact. The off rate shows that the PLC-beta 2.G beta gamma complexes are long-lived ( approximately 123 s) and that activation of PLC-beta 2 by G beta gamma would be sustained without a deactivating factor. The addition of alpha i1(GDP) subunits failed to physically dissociate the complex as determined by fluorescence. However, enzyme activity studies performed under similar conditions show that the addition of G alpha i1(GDP) results in reversal of PLC-beta 2 activation by G beta gamma during the time of the assay (30 s). From these results, we propose that G alpha(GDP) subunits can bind to the PLC-beta 2.G beta gamma complex to allow for rapid deactivation without complex dissociation. In support of this model, we show by fluorescence that G alpha i1(GDP).G beta gamma.PLC-beta 2 can form.     

Modelling tool for chemical-mechanical polishing design andevaluation

Wafer-scale phenomenological modeling, combined with an automatic model validation algorithm, has been implemented in a chemical-mechanical polishing (CMP) modeling software environment called Plane-View. The wafer-scale material removal model is an enhanced Preston equation that admits a nonuniform pressure distribution. Automatic model validation is performed using the Levenberg-Marquart minimization scheme and film thickness data. A three-step model validation procedure is established where sets of material removal profiles are automatically read by Plane-View, which then adjusts the model parameters to optimize the model's fit, creates formulae that capture the behavior of those parameters as a function of process conditions, and stores formulae in a library for easy access by users. This article describes the software architecture, the wafer-scale model, the theoretical aspects of model validation, and a demonstration of the model and validation results using a set of five test wafers     

Effect of pH and surface functionalities on the cyclic voltammetric responses of carbon-fiber microelectrodes.

Carbon electrodes are useful for the detection of oxidizable species with cyclic voltammetry. In particular, carbon-fiber microelectrodes have been employed for the measurement of several neurotransmitters in brain tissue. However, during cyclic voltammetry with carbon-fiber electrodes the current varies with changes in concentration of some inorganic cations as a result of their interaction with surface functional groups. The electrode's response to the hydronium ion is a particular concern because its voltammetric response occurs over a broad range of potentials that overlap those of neurotransmitters of interest such as dopamine. This is especially a problem in vivo because simultaneous changes of dopamine and pH frequently occur in brain tissue. In this work, voltammetric current changes are shown to arise from pH dependent shifts in the peak potentials of background voltammetric waves that arise from species confined to the carbon-fiber electrode surface. Polishing the electrode with alumina suspended in cyclohexane in an environment containing lowered oxygen, a method previously demonstrated to remove oxides from the carbon surface, leads to a substantial reduction in the sensitivity to pH changes. However, this is accompanied by a loss in signal amplitude for dopamine. The dopamine response can be restored using the cation exchanger Nafion without significantly increasing the pH response. To investigate which oxide functional groups play a direct role in the electrode's current responses to changes in pH, surface-confined carbonyl and alcohol functionalities were chemically modified. In both cases, the modification did not affect the carbon-fiber electrode's responsiveness to changes in pH. Nonetheless, the polishing technique proved to be effective in reducing pH interferences in in vivo applications.     

Prevalence and relationships of sensory taint, 5α-androstenone and skatole in fat and lean tissue from the loin (Longissimus dorsi) of barrows, gilts, sows, and boars from selected abattoirs in the United States

This study assessed prevalence of boar taint in backfat and lean of barrows, gilts, sows, and boars, collected from abattoirs, without knowledge of the farms of origin, in different regions in the United States. Concentrations of 5α-androstenone (liquid chromatography/mass spectroscopy) and skatole (liquid chromatography with fluorescent detection) in backfat were measured. A trained panel evaluated boar taint aroma in heated samples. Mean 5α-androstenone and skatole levels were low among barrows, gilts, and sows, whereas 55.8% of boars scored above a 1.0 μg/g threshold for 5α-androstenone concentrations and 34.2% were above a 0.2 μg/g threshold for skatole concentrations. Mean aroma scores for backfat and lean from barrows, gilts, and sows were low. In comparison, 59.2% of boars had elevated mean aroma scores from fat samples and 31.7% from lean. Importantly, boar taint aroma was detectable by the trained panel in at least some animals in each of the sex classes.