Canalization and Symmetry in Boolean Models for Genetic Regulatory Networks

Canalization of genetic regulatory networks has been argued to be favored by evolutionary processes due to the stability that it can confer to phenotype expression. We explore whether a significant amount of canalization and partial canalization can arise in purely random networks in the absence of evolutionary pressures. We use a mapping of the Boolean functions in the Kauffman N-K model for genetic regulatory networks onto a k-dimensional Ising hypercube to show that the functions can be divided into different classes strictly due to geometrical constraints. The classes can be counted and their properties determined using results from group theory and isomer chemistry. We demonstrate that partially canalized functions completely dominate all possible Boolean functions, particularly for higher k. This indicates that partial canalization is extremely common, even in randomly chosen networks, and has implications for how much information can be obtained in experiments on native state genetic regulatory networks.Comment: 14 pages, 4 figures; version to appear in J. Phys.

Complex epithelial remodeling underlie the fusion event in early fetal development of the human penile urethra.

We recently described a two-step process of urethral plate canalization and urethral fold fusion to form the human penile urethra. Canalization ("opening zipper") opens the solid urethral plate into a groove, and fusion ("closing zipper") closes the urethral groove to form the penile urethra. We hypothesize that failure of canalization and/or fusion during human urethral formation can lead to hypospadias. Herein, we use scanning electron microscopy (SEM) and analysis of transverse serial sections to better characterize development of the human fetal penile urethra as contrasted to the development of the human fetal clitoris. Eighteen 7-13 week human fetal external genitalia specimens were analyzed by SEM, and fifteen additional human fetal specimens were sectioned for histologic analysis. SEM images demonstrate canalization of the urethral/vestibular plate in the developing male and female external genitalia, respectively, followed by proximal to distal fusion of the urethral folds in males only. The fusion process during penile development occurs sequentially in multiple layers and through the interlacing of epidermal "cords". Complex epithelial organization is also noted at the site of active canalization. The demarcation between the epidermis of the shaft and the glans becomes distinct during development, and the epithelial tag at the distal tip of the penile and clitoral glans regresses as development progresses. In summary, SEM analysis of human fetal specimens supports the two-zipper hypothesis of formation of the penile urethra. The opening zipper progresses from proximal to distal along the shaft of the penis and clitoris into the glans in identical fashion in both sexes. The closing zipper mechanism is active only in males and is not a single process but rather a series of layered fusion events, uniquely different from the simple fusion of two epithelial surfaces as occurs in formation of the palate and neural tube

Replica symmetry breaking in an adiabatic spin-glass model of adaptive evolution

We study evolutionary canalization using a spin-glass model with replica theory, where spins and their interactions are dynamic variables whose configurations correspond to phenotypes and genotypes, respectively. The spins are updated under temperature T_S, and the genotypes evolve under temperature T_J, according to the evolutionary fitness. It is found that adaptation occurs at T_S < T_S^{RS}, and a replica symmetric phase emerges at T_S^{RSB} < T_S < T_S^{RS}. The replica symmetric phase implies canalization, and replica symmetry breaking at lower temperatures indicates loss of robustness.Comment: 5pages, 2 figure

Molecular Network Control Through Boolean Canalization

Boolean networks are an important class of computational models for molecular interaction networks. Boolean canalization, a type of hierarchical clustering of the inputs of a Boolean function, has been extensively studied in the context of network modeling where each layer of canalization adds a degree of stability in the dynamics of the network. Recently, dynamic network control approaches have been used for the design of new therapeutic interventions and for other applications such as stem cell reprogramming. This work studies the role of canalization in the control of Boolean molecular networks. It provides a method for identifying the potential edges to control in the wiring diagram of a network for avoiding undesirable state transitions. The method is based on identifying appropriate input-output combinations on undesirable transitions that can be modified using the edges in the wiring diagram of the network. Moreover, a method for estimating the number of changed transitions in the state space of the system as a result of an edge deletion in the wiring diagram is presented. The control methods of this paper were applied to a mutated cell-cycle model and to a p53-mdm2 model to identify potential control targets

Comparison of imaging with sub-wavelength resolution in the canalization and resonant tunnelling regimes

We compare the properties of subwavelength imaging in the visible wavelength range for metal-dielectric multilayers operating in the canalization and the resonant tunnelling regimes. The analysis is based on the transfer matrix method and time domain simulations. We show that Point Spread Functions for the first two resonances in the canalization regime are approximately Gaussian in shape. Material losses suppress transmission for higher resonances, regularise the PSF but do not compromise the resolution. In the resonant tunnelling regime, the MTF may dramatically vary in their phase dependence. Resulting PSF may have a sub-wavelength thickness as well as may be broad with multiple maxima and a rapid phase modulation. We show that the width of PSF may be reduced by further propagation in free space, and we provide arguments to explain this surprising observation.Comment: 17 pages,12 figure

Pseudocanalization regime for magnetic dark-field hyperlens

Hyperbolic metamaterials (HMMs) are the cornerstone of the hyperlens, which brings the superresolution effect from the near-field to the far-field zone. For effective application of the hyperlens it should operate in so-called canalization regime, when the phase advancement of the propagating fields is maximally supressed, and thus field broadening is minimized. For conventional hyperlenses it is relatively straightforward to achieve canalization by tuning the anisotropic permittivity tensor. However, for a dark-field hyperlens designed to image weak scatterers by filtering out background radiation (dark-field regime) this approach is not viable, because design requirements for such filtering and elimination of phase advancement i.e. canalization, are mutually exclusive. Here we propose the use of magnetic ($\mu$-positive and negative) HMMs to achieve phase cancellation at the output equivalent to the performance of a HMM in the canalized regime. The proposed structure offers additional flexibility over simple HMMs in tuning light propagation. We show that in this ``pseudocanalizing'' configuration quality of an image is comparable to a conventional hyperlens, while the desired filtering of the incident illumination associated with the dark-field hyperlens is preserved

The Emergence of Canalization and Evolvability in an Open-Ended, Interactive Evolutionary System

Natural evolution has produced a tremendous diversity of functional organisms. Many believe an essential component of this process was the evolution of evolvability, whereby evolution speeds up its ability to innovate by generating a more adaptive pool of offspring. One hypothesized mechanism for evolvability is developmental canalization, wherein certain dimensions of variation become more likely to be traversed and others are prevented from being explored (e.g. offspring tend to have similarly sized legs, and mutations affect the length of both legs, not each leg individually). While ubiquitous in nature, canalization almost never evolves in computational simulations of evolution. Not only does that deprive us of in silico models in which to study the evolution of evolvability, but it also raises the question of which conditions give rise to this form of evolvability. Answering this question would shed light on why such evolvability emerged naturally and could accelerate engineering efforts to harness evolution to solve important engineering challenges. In this paper we reveal a unique system in which canalization did emerge in computational evolution. We document that genomes entrench certain dimensions of variation that were frequently explored during their evolutionary history. The genetic representation of these organisms also evolved to be highly modular and hierarchical, and we show that these organizational properties correlate with increased fitness. Interestingly, the type of computational evolutionary experiment that produced this evolvability was very different from traditional digital evolution in that there was no objective, suggesting that open-ended, divergent evolutionary processes may be necessary for the evolution of evolvability.Comment: SI can be found at: http://www.evolvingai.org/files/SI_0.zi

Magnification of Subwavelength Field Distributions at Microwave Frequencies Using a Wire Medium Slab Operating in the Canalization Regime

Magnification of subwavelength field distributions using a wire medium slab operating in the canalization regime is demonstrated using numerical simulations. The magnifying slab is implemented by radially enlarging the distance between adjacent wires, and the operational frequency is tuned to coincide with the Fabry-Perot resonance condition. The near-field distribution of a complex-shaped source is canalized over an electrical distance corresponding roughly to $3\lambda$, and the distribution details are magnified by a factor of three. The operation of the slab is studied at several frequencies deviating from the Fabry-Perot resonance.Comment: 7 pages, 2 figure