Perspective │2 Artificial intelligence (AI) tools are increasingly being applied in drug discovery. Whilst some protagonists point to vast opportunities potentially offered by such tools, others remain skeptical, waiting for a clear impact to be shown in drug discovery projects. The truth is probably somewhere between these extremes, but it is clear that AI is providing new challenges not only for the scientists involved but also for the biopharma industry and its established processes for discovering and developing new medicines. This article presents the views of a diverse group of international experts on the 'grand challenges' for small-molecule drug discovery with AI and approaches to address them.

The aim of this paper is the introduction and comparison of consistent albeit passive mechanical models for the whole cochlea. A widely used transmission line filterbank, which hydrodynamically speaking is a long wave approximation (L model), suffers from a well-known inconsistency: its main modeling assumption is not valid within the resonance region, where most of the overall excitation takes place. In the present paper two approaches to overcome this inconsistency are discussed. One model is the average pressure (AP) model by Duifhuis, the other is obtained by a combination of a long and a short wave approximation (LS model). Considerable differences between the L and the LS model are observed. All models are compared by inserting them into the full integral equation obtained from the hydrodynamic equations and the boundary conditions. Here the LS model fares better than the AP model for small damping, whereas the opposite is true for higher damping. As expected, the L model fails badly in the resonance region.

Rupp A, Sieroka N, Gutschalk A, Dau T. Representation of auditory-filter phase characteristics in the cortex of human listeners. J Neurophysiol 99: 1152-1162, 2008. First published January 9, 2008 doi:10.1152/jn.00778.2007. Harmonic tone complexes with component phases, adjusted using a variant of a method proposed by Schroeder, can produce pure-tone masked thresholds differing by Ͼ20 dB. This phenomenon has been qualitatively explained by the phase characteristics of the auditory filters on the basilar membrane, which differently affect the flat envelopes of the Schroeder-phase maskers. We examined the influence of auditory-filter phase characteristics on the neural representation in the auditory cortex by investigating cortical auditory evoked fields (AEFs). We found that the P1m component exhibited larger amplitudes when a long-duration tone was presented in a repeating linearly downward sweeping (Schroeder positive, or m ϩ ) masker than in a repeating linearly upward sweeping (Schroeder negative, or m Ϫ ) masker. We also examined the neural representation of short-duration tone pulses presented at different temporal positions within a single period of three maskers differing in their component phases (m ϩ , m Ϫ , and sine phase m 0 ). The P1m amplitude varied with the position of the tone pulse in the masker and depended strongly on the masker waveform. The neuromagnetic results in all cases were consistent with the perceptual data obtained with the same stimuli and with results from simulations of neural activity at the output of cochlear preprocessing. These findings demonstrate that phase effects in peripheral auditory processing are accurately reflected up to the level of the auditory cortex. I N T R O D U C T I O NOne of the earliest and most fundamental stages of auditory processing is the frequency analysis that takes place in the cochlea. This stage has often been modeled by a bank of overlapping filters, and much effort has gone into characterizing the magnitude response of the "auditory filters" (e.g., Fletcher 1940;Glasberg and Moore 1990;Patterson 1976;Plomp 1964;Zwicker et al. 1957). Conversely, filter phase responses received much less attention, partly due to the popular belief that the ear is essentially "phase deaf" (Helmholtz 1954) and the observation that many perceptual properties can be explained by analyzing the power spectrum of a sound-i.e., by discarding the phase information. Although a number of studies have since shown that the ear is sensitive to changes in stimulus phase, both within an auditory filter (Goldstein 1967;Mathes and Miller 1947;Zwicker 1952) and, to a lesser extent, across filters (Patterson 1987), they have mostly assumed that any effect of the auditory filters themselves on the stimulus phase can be ignored. Indeed, there are only certain aspects of the phase response that have any psychophysically measurable influence. For instance, both the absolute phase and the group delay, proportional to d/df, are generally meaningful only in the context of a fixed time ref...

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