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One of the FDA s goals for the PAT guidance is to tailor the Agency s usual regulatory scrutiny to meet the needs of PAT-based innovations that (1) improve the scienti c basis for establishing regulatory speci cations, (2) promote continuous improvement, and (3) improve manufacturing while maintaining or improving the current level of product quality. Recognizing that the achievement of this goal requires a unique interface between regulators and manufacturers seeking to implement PAT, a strategy for implementation based on the integrated systems approach was developed. An objective of the strategy for implementation is to facilitate clear, effective, and meaningful communication between the agency and industry, for example, in the form of meetings or informal communication. In practice, the strategy breaks with traditional industry FDA modes of communication; whenever PAT is concerned, it is anticipated that regulators will communicate directly with the pharmaceutical scientists and engineers involved with development and operation of the PAT system rather than indirectly via a department of regulatory affairs. The components of the agency s regulatory strategy include:

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35. J. Litva and T. Lo. Digital Beamforming in Wireless Communications, pages (a): 13-34, (b): 57-91, (c) 13-27. Artech House, 1996. 36. R. Piechocki, N. Canagarajah, J. McGeehan, and G. Tsoulos. Orthogonal re-spread for uplink wcdma beamforming. IEEE Vehicular Technology Conference]May 2000. 37. M. Bengtsson and B. Ottersten. Optimum downlink beamforming using semidefinite optimisation. 37th Annual Allerton Conference on Communication, Control and Computing, June 1999. 38. H. Krim and M. Viberg. Two decades of array signal processing. IEEE Signal Processing Magazine, July 1996. 39. M. Bartlett. Smoothing periodograms from time series with continuous spectra. Nature, (161), 1948. 40. J. Capon. High resolution frequency-wavenumber spectrum analysis. IEEE Proceedings, 57(8), August 1969. 41. R. Schmidt. A subspace approach to multiple emitter location and spectral estimation. PhD Thesis, University of Stanford, 1981. 42. J. Bohme. Estimation of source parameters by maximum likelihood and non-linear regression. IEEE Conference of Acoustics, Speech and Signal Processing, pages 731-734, 1984. 43. A. Swindlehurst and P. Stoica. Maximum likelihood methods in radar array signal processing. IEEE Proceedings, 86(2):421-441, 1998. 44. A. Paulraj, R. Roy, and T. Kailath. A subspace rotation approach to signal parameter estimation. IEEE Proceedings, 74(7):1044-1045, July 1986. 45. J . Fessler and H. Hero. Space alternating generalised expectation maximisation algorithm. IEEE Transactions on Signal Processing, 42(10):2664-2677, October 1994. 46. M. Viberg, B. Ottersten, and T. Kailath. Detection and estimation in sensor arrays based on weighted subspace fitting. IEEE Transactions on Signal Processing, 39( 11):2436-22449, November 1991. 47. M. Haardt and J. Nossek. Unitary esprit: How to obtain increased estimation accuracy with reduced computational burden. IEEE Transactions on Signal Processing, 43(5):1232-1242, May 1995. 48. B. Widrow and S. D Stearns. Adaptive Signal Processing. Prentice Hall, 1985.

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make it easy to integrate the state and methods of a service into a single component. Event handler functions. Another strategy for associating an event handler with a handle is to register a pointer to a function with a reactor rather than an object. Using a pointer to a function as the dispatching target makes it convenient to register callbacks without having to define a new subclass that inherits from an event handler base class.

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1 Small population size improved initial performance while large population size improved long-term performance, 50 Npop 100 2 High mutation rate was good for off-line performance, while low mutation rate was good for on-line performance, m = 0001 3 Crossover rates should be about Xrate = 060 4 Type of crossover (single point vs multipoint) made little difference A decade later brought signi cant improvements to computers that led to the next important study done by Grefenstette (1986) He used a metagenetic algorithm to optimize the on-line and off-line performance of GAs based on varying six parameters: Npop, Xrate, m, G, scaling window, and whether or not elitism is used A scaling window determines just how a cost is scaled relative to other costs in the population The metagenetic algorithm used Npop = 50, Xrate = 06, m = 0.

along the optical axes should be recognized in the numerical calculations of the SBS process. In the simplest case the change of the diameter of the focused pump light can be considered in a very simple way as it was shown in Ref. 2. The varying focus along the z axis can be recognized by the change of the cross section A[z] leading to the following set of equations: p @IP (z, t) n @IP (z, t) IP @A(z) S(z, t) IP IS @z c0 @t A(z) @z p @IS (z, t) n @IS (z, t) IS @A(z) S(z, t) IP IS @z c0 @t A(z) @z o @S(z, t) 1 n p gB IP IS S(z, t) S0 @t 2t B

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