Analog VLSI model of binaural hearing

The stereausis model of biological auditory processing is proposed as a representation that encodes both binaural and spectral information in a unified framework. A working analog VLSI chip that implements this model of early auditory processing in the brain is described. The chip is a 100000-transistor integrated circuit that computes the stereausis representation in real time, using continuous-time analog processing. The chip receives two audio inputs, representing sound entering the two ears, computes the stereausis representation, and generates output signals that can directly drive a color CRT display. Outputs from the chips for a variety of artificial and speech stimuli are shown.     

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine as a substrate of cytochrome P450 2D6: allosteric effects of NADPH-cytochrome P450 reductase

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a neurotoxin that produces Parkinsonism symptoms in man, has been examined as a substrate of recombinant human cytochrome P450 2D6. When cumene hydroperoxide is used as an oxygen and electron donor, a single product is formed, identified as 4-phenyl-1,2,3,6-tetrahydropyridine. The K(m) for formation of this product (130 microM) is in agreement with the dissociation constants for MPTP binding to the enzyme determined by optical and nuclear magnetic resonance (NMR) spectroscopy. When the reaction is carried out with nicotinamide adenine dinucleotide phosphate (reduced) (NADPH) and recombinant human NADPH-cytochrome P450 reductase, a second product, identified as 1-methyl-4-(4'-hydroxyphenyl)-1,2,3,6-tetrahydropyridine, is formed in addition to 4-phenyl-1,2,3,6-tetrahydropyridine. The K(m) values for formation of these two products are 19 microM and 120 microM, respectively. Paramagnetic relaxation experiments have been used to measure distances between the protons of bound MPTP and the heme iron, and these have been used to construct models for the position and orientation of MPTP in the active site. For the cytochrome alone, a single mode of binding was observed, with the N-methyl close to the heme iron in a position appropriate for the observed N-demethylation reaction. In the presence of the reductase, the data were not consistent with a single mode of binding but could be explained by the existence of two alternative orientations of MPTP in the active site. One of these, characterized by a dissociation constant of 150 microM, is essentially identical to that observed in the absence of the reductase. In the second, which has a K(d) of 25 microM, the MPTP is oriented so that the aromatic ring is close to the heme iron, in a position appropriate for p-hydroxylation leading to the formation of the product seen only in the presence of the reductase. In the case of codeine, another substrate for cytochrome P450 2D6, the addition of reductase had no effect on the nature of the product formed, the dissociation constant, or the orientation in the binding site. These observations show that NADPH-cytochrome P450 reductase has an allosteric effect on the active site of cytochrome P450 2D6 that affects the binding of some substrates but not others.     

A Low-Power Wide-Dynamic-Range Analog VLSI Cochlea

Low-power wide-dynamic-range systems are extremely hard to build. The biological cochlea is one of the most awesome examples of such a system: It can sense sounds over 12 orders of magnitude in intensity, with an estimated power dissipation of only a few tens of microwatts. In this paper, we describe an analog electronic cochlea that processes sounds over 6 orders of magnitude in intensity, and that dissipates 0.5 mW. This 117-stage, 100 Hz to 10 KHz cochlea has the widest dynamic range of any artificial cochlea built to date. The wide dynamic range is attained through the use of a wide-linear-range transconductance amplifier, of a low-noise filter topology, of dynamic gain control (AGC) at each cochlear stage, and of an architecture that we refer to as overlapping cochlear cascades. The operation of the cochlea is made robust through the use of automatic offset-compensation circuitry. A BiCMOS circuit approach helps us to attain nearly scale-invariant behavior and good matching at all frequencies. The synthesis and analysis of our artificial cochlea yields insight into why the human cochlea uses an active traveling-wave mechanism to sense sounds, instead of using bandpass filters. The low power, wide dynamic range, and biological realism make our cochlea well suited as a front end for cochlear implants.