Evaluating the federal role in financing health-related research

This paper considers the appropriate role for government in the support of scientific and technological progress in health care; the information the federal government needs to make well-informed decisions about its role; and the ways that federal policy toward research and development should respond to scientific advances, technology trends, and changes in the political and social environment. The principal justification for government support of research rests upon economic characteristics that lead private markets to provide inappropriate levels of research support or to supply inappropriate quantities of the products that result from research. The federal government has two basic tools for dealing with these problems: direct subsidies for research and strengthened property rights that can increase the revenues that companies receive for the products that result from research. In the coming years, the delivery system for health care will continue to undergo dramatic changes, new research opportunities will emerge at a rapid pace, and the pressure to limit discretionary federal spending will intensify. These forces make it increasingly important to improve the measurement of the costs and benefits of research and to recognize the tradeoffs among alternative policies for promoting innovation in health care.

The corticofugal system for hearing: Recent progress

Peripheral auditory neurons are tuned to single frequencies of sound. In the central auditory system, excitatory (or facilitatory) and inhibitory neural interactions take place at multiple levels and produce neurons with sharp level-tolerant frequency-tuning curves, neurons tuned to parameters other than frequency, cochleotopic (frequency) maps, which are different from the peripheral cochleotopic map, and computational maps. The mechanisms to create the response properties of these neurons have been considered to be solely caused by divergent and convergent projections of neurons in the ascending auditory system. The recent research on the corticofugal (descending) auditory system, however, indicates that the corticofugal system adjusts and improves auditory signal processing by modulating neural responses and maps. The corticofugal function consists of at least the following subfunctions. (i) Egocentric selection for short-term modulation of auditory signal processing according to auditory experience. Egocentric selection, based on focused positive feedback associated with widespread lateral inhibition, is mediated by the cortical neural net working together with the corticofugal system. (ii) Reorganization for long-term modulation of the processing of behaviorally relevant auditory signals. Reorganization is based on egocentric selection working together with nonauditory systems. (iii) Gain control based on overall excitatory, facilitatory, or inhibitory corticofugal modulation. Egocentric selection can be viewed as selective gain control. (iv) Shaping (or even creation) of response properties of neurons. Filter properties of neurons in the frequency, amplitude, time, and spatial domains can be sharpened by the corticofugal system. Sharpening of tuning is one of the functions of egocentric selection.

Progress toward chemical accuracy in the computer simulation of condensed phase reactions.

We describe a procedure for the generation of chemically accurate computer-simulation models to study chemical reactions in the condensed phase. The process involves (i) the use of a coupled semiempirical quantum and classical molecular mechanics method to represent solutes and solvent, respectively; (ii) the optimization of semiempirical quantum mechanics (QM) parameters to produce a computationally efficient and chemically accurate QM model; (iii) the calibration of a quantum/classical microsolvation model using ab initio quantum theory; and (iv) the use of statistical mechanical principles and methods to simulate, on massively parallel computers, the thermodynamic properties of chemical reactions in aqueous solution. The utility of this process is demonstrated by the calculation of the enthalpy of reaction in vacuum and free energy change in aqueous solution for a proton transfer involving methanol, methoxide, imidazole, and imidazolium, which are functional groups involved with proton transfers in many biochemical systems. An optimized semiempirical QM model is produced, which results in the calculation of heats of formation of the above chemical species to within 1.0 kcal/mol (1 kcal = 4.18 kJ) of experimental values. The use of the calibrated QM and microsolvation QM/MM (molecular mechanics) models for the simulation of a proton transfer in aqueous solution gives a calculated free energy that is within 1.0 kcal/mol (12.2 calculated vs. 12.8 experimental) of a value estimated from experimental pKa values of the reacting species.

Speech technology in 2001: new research directions.

Research in speech recognition and synthesis over the past several decades has brought speech technology to a point where it is being used in "real-world" applications. However, despite the progress, the perception remains that the current technology is not flexible enough to allow easy voice communication with machines. The focus of speech research is now on producing systems that are accurate and robust but that do not impose unnecessary constraints on the user. This chapter takes a critical look at the shortcomings of the current speech recognition and synthesis algorithms, discusses the technical challenges facing research, and examines the new directions that research in speech recognition and synthesis must take in order to form the basis of new solutions suitable for supporting a wide range of applications.