Current methods for site-directed structure generation

Summary There has been a rapid growth of interest in techniques for site-directed drug design, fuelled by the increasing availability of structural models of proteins of therapeutic importance, and by studies reported in the literature showing that potent chemical leads can be obtained by these techniques. Structure generation programs offer the prospect of discovering highly original lead structures from novel chemical families. Due to the fact that this technique is more-or-less still in its infancy, there are no case studies available that demonstrate the use of structure generation programs for site-directed drug design. Such programs were first proposed in 1986, and became commercially available in early 1992. They have shown their ability to reproduce, or suggest reasonable alternatives for, ligands in well-defined binding sites. This brief review will discuss the recent advances that have been made in the field of site-directed structure generation.     

Load-capacity interference and the bathtub curve

Load-capacity (stress-strength) interference theory is used to derive a heuristic failure rate for an item subjected to repetitive loading which is Poisson distributed in time. Numerical calculations are performed using Gaussian distributions in load and capacity. Infant mortality, constant failure rate (Poisson failures), and aging are shown to be associated with capacity variability, load variability, and capacity deterioration, respectively. Bathtub-shaped failure rate curves are obtained when all three failure types are present. Changes in load or capacity distribution parameters often strongly affect the quantitative behavior of the failure-rate curves, but they do not affect the qualitative behavior of the bathtub curve. Neither is it likely that the qualitative behavior will be affected by the use of nonGaussian distributions. The numerical results, however, indicate that infant mortality and wear-out failures interact strongly with load variability. Thus bathtub curves arising from this model cannot be represented as simple superpositions of independent contributions from the three failure types. Only if the three failure types arise from independent failure mechanisms or in different components is it legitimate simply to sum the failure rate contributions     

Solution of nonlinear kinematics of a parallel-link constrained Stewart platform manipulator

The Stewart platform manipulator is a fully parallel kinematic linkage system that has great advantages over typical serial link robots. However, one major problem in controlling this kind of manipulator is that, due to its closed kinematic chain and parallel-link constrained structure, it is impossible to derive an explicit kinematic solution. This paper proposes a simplified algorithm to numerically solve the forward kinematics of a six-links Stewart platform. Taking advantage of some fundamental geometric operations, the proposed algorithm involves only 3 nonlinear simultaneous equations. The explicit expressions are derived for some special configurations which can directly give the geometric limitations to motion in terms of the geometric dimensions of the platforms and the legs.Research was supported by Texas Advanced Technology program under grant 003656-008 and National Science Foundation under grant MSS9211970.     

Miller compensation using current buffers in fully differential CMOS two-stage operational amplifiers

Several Miller compensation schemes using a current buffer in series with the compensation capacitor to modify the right-half-plane zero in fully differential two-stage CMOS operational amplifiers are analyzed. One scheme uses a current mirror as a current buffer, while the rest use a common-gate transistor as a current buffer. The gain transfer functions are derived for each topology, and approximate transfer-function coefficients are found that allow accurate estimation of the zero(s) and poles.     

Partially finite convex programming,Part I: Quasi relative interiors and duality theory

We study convex programs that involve the minimization of a convex function over a convex subset of a topological vector space, subject to a finite number of linear inequalities. We develop the notion of the quasi relative interior of a convex set, an extension of the relative interior in finite dimensions. We use this idea in a constraint qualification for a fundamental Fenchel duality result, and then deduce duality results for these problems despite the almost invariable failure of the standard Slater condition. Part II of this work studies applications to more concrete models, whose dual problems are often finite-dimensional and computationally tractable.     

A 30-b integrated logarithmic number system processor

The authors describe an integrated processor that performs addition and subtraction of 30-b numbers in the logarithmic number system (LNS). This processor offers 5-MOPS performance in 3-μm CMOS technology, and is implemented in a two-chip set comprising 170 K transistors. Two techniques are used to achieve this precision in a moderate circuit area. Linear approximation of the LNS arithmetic functions using logarithmic arithmetic is shown to be simple due to the particular functions involved. A segmented approach to linear approximation minimizes the amount of table space required. Subsequent nonlinear compression of each lookup table leads to a further reduction in table size. The result is that a factor of 285 reduction in table size is achieved, compared to previous techniques. The circuit area of the implementation is minimized by optimizing the table parameters, using a computer program that accurately models ROM area. The implementation is highly pipelined, and produces one result per clock cycle using a ten-stage pipeline     

Optimally Dense Packings of Hyperbolic Space

In previous work, a probabilistic approach to controlling difficulties of density in hyperbolic space led to a workable notion of optimal density for packings of bodies. In this paper we extend an ergodic theorem of Nevo to provide an appropriate definition of those packings to be considered optimally dense. Examples are given to illustrate various aspects of the density problem, in particular the shift in emphasis from the analysis of individual packings to spaces of packings.