Uncovering New Functions for MicroRNAs in \u3cem\u3eCaenorhabditis elegans\u3c/em\u3e

In the race to understand microRNA (miRNA) functions in development and physiology, Caenorhabditis elegans investigators were the first out of the gate with the cloning and analysis of the lin-4 and let-7 miRNAs [1,2]. The starting point of strong, penetrant loss of function phenotypes facilitated these advancements. However, subsequent functional analysis of miRNAs in C. elegans was hampered by the lack of easily observable loss-of-function phenotypes [3]. There are several possible models to account for this observation. First, redundancy between related miRNAs can account for the absence of phenotypes in mutants missing individual miRNA genes [4,5]. Second, miRNAs may also function redundantly with unrelated miRNAs or other regulatory mechanisms. Third, identification of miRNA functions may require the analysis of specific cells during development, assays typically not included in initial broad phenotypic analyses. For example, the lsy-6 miRNA is an essential regulator of a chemosensory neuron cell fate in C. elegans [6]. Such a specialized function would not have been identified in broad phenotypic analyses. Finally, miRNAs may act to ‘fine-tune’ gene expression, to maintain protein levels of targets in an optimal range. Loss of this relatively minor regulatory input by miRNAs would not be expected to result in penetrant, observable defects under normal conditions. Recent work has analyzed the functions of individual miRNAs under conditions of environmental or physiological stress. With these approaches, functions for individual miRNAs, which remain elusive under normal growth conditions, have been uncovered. These stresses can be introduced through genetic mutations, environmental perturbations, or through the normal aging process. These results are consistent with the hypothesis that miRNAs act to ensure the robustness of developmental or physiological pathways [7]

The physical basis for Parrondo's games

Several authors have implied that the original inspiration for Parrondo's games was a physical system called a ``flashing Brownian ratchet''. The relationship seems to be intuitively clear but, surprisingly, has not yet been established with rigor. In this paper, we apply standard finite-difference methods of numerical analysis to the Fokker-Planck equation. We derive a set of finite difference equations and show that they have the same form as Parrondo's games. Parrondo's games, are in effect, a particular way of sampling a Fokker-Planck equation. Physical Brownian ratchets have been constructed and have worked. It is hoped that the finite element method presented here will be useful in the simulation and design of flashing Brownian ratchets.Comment: 10 pages and 2 figure

Parrondo's games with chaotic switching

This paper investigates the different effects of chaotic switching on Parrondo's games, as compared to random and periodic switching. The rate of winning of Parrondo's games with chaotic switching depends on coefficient(s) defining the chaotic generator, initial conditions of the chaotic sequence and the proportion of Game A played. Maximum rate of winning can be obtained with all the above mentioned factors properly set, and this occurs when chaotic switching approaches periodic behavior.Comment: 11 pages, 9 figure

Optimizing genetic algorithm strategies for evolving networks

This paper explores the use of genetic algorithms for the design of networks, where the demands on the network fluctuate in time. For varying network constraints, we find the best network using the standard genetic algorithm operators such as inversion, mutation and crossover. We also examine how the choice of genetic algorithm operators affects the quality of the best network found. Such networks typically contain redundancy in servers, where several servers perform the same task and pleiotropy, where servers perform multiple tasks. We explore this trade-off between pleiotropy versus redundancy on the cost versus reliability as a measure of the quality of the network.Comment: 9 pages, 5 figure