Optimization of an ether series of mGluR5 positive allosteric modulators: Molecular determinants of MPEP site interaction crossover

We report the optimization of a series of non-MPEP site metabotropic glutamate receptor 5 (mGlu5) pos. allosteric modulators (PAMs) based on a simple acyclic ether series. Modifications led to a gain of MPEP site interaction through incorporation of a chiral amide in conjunction with a nicotinamide core. A highly potent PAM, 8v (VU0404251), was shown to be efficacious in a rodent model of psychosis. These studies suggest that potent PAMs within topol. similar chemotypes can be developed to preferentially interact or not interact with the MPEP allosteric binding site.

Optimization of Composite Structures to Delay Mode Jump Instabilities

Numerous studies have shown that postbuckling stiffened panels may undergo abrupt changes in buckled mode
shape when loaded in uniaxial compression. This phenomenon is often referred to as a mode jump or secondary
instability. The resulting sudden release of stored energy may initiate damage in vulnerable regions within a
structure, for example, at the skin-stiffener interface of a stiffened composite panel. Current design practice is to
remove a mode jump by increasing the skin thickness of the postbuckling region. A layup optimization methodology,
based on a genetic algorithm, is presented, which delays the onset of secondary instabilities in a composite structure
while maintaining a constant weight and subject to a number of design constraints. A finite element model was
developed of a stiffened panel’s skin bay, which exhibited secondary instabilities. An automated numerical routine
extracted information directly from the finite element displacement results to detect the onset of initial buckling and
secondary instabilities. This routine was linked to the genetic algorithm to find a revised layup for the skin bay, within
appropriate design constraints, to delay the onset of secondary instabilities. The layup optimization methodology,
resulted in a panel that had a higher buckling load, prebuckling stiffness, and secondary instability load than the
baseline design.

Optimization strategy for minimizing damage in postbuckling stiffened panels

Composite materials are finding increasing use on primary aerostructures to meet demanding performance targets while reducing environmental impact. This paper presents a finite-element-based preliminary optimization methodology for postbuckling stiffened panels, which takes into account damage mechanisms that lead to delamination and subsequent failure by stiffener debonding. A global-local modeling approach is adopted in which the boundary conditions on the local model are extracted directly from the global model. The optimization procedure is based on a genetic algorithm that maximizes damage resistance within the postbuckling regime. This routine is linked to a finite element package and the iterative procedure automated. For a given loading condition, the procedure optimized the stacking sequence of several areas of the panel, leading to an evolved panel that displayed superior damage resistance in comparison with nonoptimized designs.

Multiple cutout optimization in composite plates using evolutionary structural optimization

The optimization of cutouts in composite plates was investigated by implementing a procedure known as Evolutionary Structural Optimization. Perforations were introduced into a finite element mesh of the plate from which one or more cutouts of a predetermined size were evolved. In the examples presented, plates were rejected from around each evolving cutout based on a predefined rejection criterion. The Limiting ply within each plate element around the cutout was determined based on the Tsai-Hill failure criterion. Finite element plates with values below the product of the average Tsai-Hill number and a rejection criterion were subsequently removed. This process was iterated until a steady state was reached and the rejection criterion was then incremented by an evolutionary rate and the above steps repeated until the desired cutout area was achieved. Various plates with differing lay-up and loading parameters were investigated to demonstrate the generality and robustness of this optimization procedure.

Shape optimization of interior cutouts in composite panels

This paper presents validated results of the optimization of cutouts in laminated carbon-fibre composite panels by adapting a recently developed optimization procedure known as Evolutionary Structural Optimization (ESO). An initial small cutout was introduced into each finite element model and elements were removed from around this cutout based on a predefined rejection criterion. In the examples presented, the limiting ply within each plate element around the cutout was determined based on the Tsai-Hill failure index. Plates with values below the product of the average Tsai-Hill number and a rejection ratio (RR) were subsequently removed. This process was iterated until a steady state was reached and the RR was then incremented by an evolutionary rate (ER). The above steps were repeated until a cutout of a desired area was achieved.

Lay-up optimization of composite plates to delay mode-jump instabilities

Experimental and numerical studies have shown that the occurrence of abrupt secondary instabilities, or mode-jumps, in a postbuckling stiffened composite panel may initiate structural failure. This study presents an optimisation methodology, using a genetic algorithm and finite element analysis for the lay-up optimisation of postbuckling composite plates to delay the onset of mode-jump instabilities. A simple and novel approach for detecting modejumps is proposed, based on the RMS value of out-of-plane pseudo-velocities at a number of locations distributed over the postbuckling structure

Design, optimization and characterisation of polymeric microneedle arrays prepared by a novel laser-based micromoulding technique

Design and evaluation of a novel laser-based method for micromoulding of microneedle arrays from polymeric materials under ambient conditions. The aim of this study was to optimise polymeric composition and assess the performance of microneedle devices that possess different geometries.

Optimization of Weighted Finite State Transducer for Speech Recognition

There is considerable interest in creating embedded, speech recognition hardware using the weighted finite state transducer (WFST) technique but there are performance and memory usage challenges. Two system optimization techniques are presented to address this; one approach improves token propagation by removing the WFST epsilon input arcs; another one-pass, adaptive pruning algorithm gives a dramatic reduction in active nodes to be computed. Results for memory and bandwidth are given for a 5,000 word vocabulary giving a better practical performance than conventional WFST; this is then exploited in an adaptive pruning algorithm that reduces the active nodes from 30,000 down to 4,000 with only a 2 percent sacrifice in speech recognition accuracy; these optimizations lead to a more simplified design with deterministic performance.