Adaptive walks with noisy fitness measurements

Summary Adaptive walks constitute an optimization technique for searching a space of possible solutions, for example, a space of different molecules. The goal is to find a point in space (a molecule) that is optimal or near-optimal in some property, generally referred to as the fitness, such as its ability to bind to a given receptor. Adaptive walking, an analog of natural selection, is a powerful technique for searching landscapes. However, errors in the measurements will cause errors in the adaptive walks. Mutant molecules of higher fitness may be ignored or mutants of lower fitness may be accepted. To examine the effect of measurement error on adaptive walks, we simulate single-agent hill-climbing walks on NK landscapes of varying ruggedness where Gaussian noise is added to the fitness values to model measurement error. We consider both constant measurement noise and noise whose variance decays exponentially with fitness. We show that fitness-independent noise can cause walks to melt off the peaks in a landscape, wandering in larger regions as the noise increases. However, we also show that a small amount of noise actually helps the walk perform better than with no noise. For walks in which noise decreases exponentially with fitness, the most characteristic behavior is that the walk meanders throughout the landscape until it stumbles across a point of relatively high fitness, then it climbs the landscape towards the nearest peak. Finally, we characterize the balance between selection pressure and noise and show that there are several classes of walk dynamic behavior.     

New cytotoxic salinosporamides from the marine Actinomycete Salinispora tropica

An extensive study of the secondary metabolites produced by the obligate marine actinomycete Salinispora tropica (strain CNB-392), the producing microbe of the potent proteasome inhibitor salinosporamide A (1), has led to the isolation of seven related gamma-lactams. The most important of these compounds were salinosporamide B (3), which is the deschloro-analogue of 1, and salinosporamide C (4), which is a decarboxylated pyrrole analogue. New SAR data for all eight compounds, derived from extensive testing against the human colon carcinoma HCT-116 and the 60-cell-line panel at the NCI, indicate that the chloroethyl moiety plays a major role in the enhanced activity of 1.     

Measurement of the absolute hohlraum-wall albedo under ignition foot drive conditions

We present measurements of the absolute albedos of hohlraums made from gold or from high-Z mixtures. The measurements are performed over the range of radiation temperatures (70-100 eV) expected during the foot of an indirect-drive temporally shaped ignition laser pulse, where accurate knowledge of the wall albedo (i.e., soft x-ray wall reemission) is most critical for determining capsule radiation symmetry. We find that the gold albedo agrees well with calculations using the supertransition array opacity model, potentially providing additional margin for inertial confinement fusion ignition.     

Syntheses and photophysical properties of fluorescent dibenzofurans,a dibenzothiophene,and carbazoles substituted with benzoxazole and hydroxyl groups to produce excited state intramolecular proton-transfer

Dibenzofurans, a dibenzothiophene, and carbazoles, each substituted with a 2-benzoxazolyl group as well as an ortho-hydroxyl group, were synthesized to produce fluors with fluorescence due to excited-state intramolecular proton-transfer. The orientations for Friedel-Crafts acylation of 3-methoxydibenzothio-phene and of the analogous carbazole were determined. The fluors displayed absorption peaks in the 330–385 nm region with molar extinction coefficients up to 57,000. Fluorescence quantum efficiencies of 0.17–0.44 were obtained at wavelengths that had peak values from 540–600 nm. The fluors are of potential use as wavelength shifters in scintillating polystyrene fibers.