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B Levitan

Publications and source records attributed to B Levitan.

9 recordsLinked to original sources
PubMed1998

Stochastic modeling and optimization of phage display.

Phage display, SELEX and other methods of combinatorial chemistry have become very popular means of finding ligands with high affinities to given targets. Despite their success, they suffer from numerous sources of error and bias, such as very low initial concentrations of species, non-specific binding, and the sampling of only a tiny fraction of the library at the end of an experiment. To understand the interaction of these errors and to better devise molecular search strategies that take the errors into account, I devise and analyze a highly detailed model of phage display. The model is specifically designed to study the influence of the stochastic nature of each laboratory step. The model includes phage multivalency, multiple classes of targets, and solid-phase equilibrium and washing, yet it is amenable to analytic results and rapid computer simulation. With both analytic and simulation approaches, I: (1) describe the effects of target concentration, phage valency, degree of background binding and other laboratory parameters on the probabilities of phage binding and of being selected; (2) show the effects of an increasing selection stringency strategy and how it results in a tradeoff between rapid library enrichment and high probability of sampling the best ligands; and (3) show how the number of phage sampled for detailed study at the end of a search alters search success. The work concludes with several practical suggestions for the control of selection stringency.

Bacteriophage M13↗
PubMed1996

Parallel cone bipolar to on-beta ganglion cell pathways in the cat retina: spatial responses, spatial aliasing, and spatial variance.

An important issue in understanding the retina is finding candidate functional roles for different cell pathways and the details of their anatomy and physiology. We consider various spatial properties of the three main cone ==> cone bipolar cell ==> on-beta ganglion cell pathways in the cat retina and possible roles for the particulars of their anatomy. The cone bipolar cells in these pathways have distinct morphologies and modest differences in their convergence, divergence, densities, and synaptic weighting; and it is unclear whether the pathways differ in their spatial properties or in some other manner. Since differences in spatial processing of cells are best studied on a systemwide level, we developed the multirate filter-based method of retinal modeling, a technique for relating the anatomy of multiple cell layers to its systemic effects. We demonstrate that (1) despite the anatomic distinctions among the three main cone bipolar cell pathways, their spatial responses are essentially identical; (2) despite the spatial averaging in the pathways, there is essentially no filtering of the nonaliasing signal components after the cone layer; (3) instead, this averaging combined with prefiltering by the eye's optics and cone gap junctions prevents spatial aliasing; and (4) the averaging and prefiltering combined allow cell responses to be similar despite significant cell-to-cell anatomic differences.

Animals↗
PubMed1995

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Journal Article↗
PubMed1995

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Journal Article↗
PubMed1995

Adaptive walks with noisy fitness measurements.

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.

Algorithms↗
PubMed1993

Signal sampling and propagation through multiple cell layers in the retina: modeling and analysis with multirate filtering.

The retina is a multilayered structure. Each layer consists of one or more classes of cell, each at its own density and with its own anatomic and physiologic properties. Signals converge from many cells in one layer onto single cells in another layer, and a signal from a single cell diverges to many cells in the next layer. In this methods paper we develop a general approach to retinal analysis and modeling that incorporates multiple cell classes, their densities, and related anatomic properties. The method is based on multirate filtering, a branch of signal processing in which signals of different sampling rates are manipulated. By drawing a correspondence between cell density and signal sampling rate, we define multirate models that incorporate different cell densities, convergence, divergence, variation in dendritic field shape, cell-to-cell variation in synaptic weights, and other anatomic features. We develop the multirate approach and apply it to the cat cone-->cone bipolar CBb1-->on-beta ganglion cell pathway as an example. We calculate the spatial frequency responses of the CBb1 and on-beta cells based on the cone spatial frequency response and find that the attenuation of high frequencies in the cones prevents aliasing that would otherwise occur in CBb1 and on-beta cells. We compare the calculations with cat psychophysics. We show that the optics of the cat eye are insufficient in themselves for the prevention of aliasing in these cells; additional attenuation by the cone-cone gap junctions and the cone aperture is necessary. By including this postreceptoral filtering, we demonstrate that the highest spatial frequency that can be passed by the retina without aliasing is determined not always only by the densities of cones, bipolar cells, and ganglion cells but also by the synaptic and the dendritic weighting between these cells.

Animals↗