Flexible and robust networks

We consider networks with two types of nodes. The v-nodes, called centers, are hyper- connected and interact one to another via many u-nodes, called satellites. This central- ized architecture, widespread in gene networks, possesses two fundamental properties. Namely, this organization creates feedback loops that are capable to generate practically any prescribed patterning dynamics, chaotic or periodic, or having a number of equilib- rium states. Moreover, this organization is robust with respect to random perturbations of the system.Comment: Journal of Bioinformatics and Computational Biology, in pres

Synthetic in vitro transcriptional oscillators

The construction of synthetic biochemical circuits from simple components illuminates how complex behaviors can arise in chemistry and builds a foundation for future biological technologies. A simplified analog of genetic regulatory networks, in vitro transcriptional circuits, provides a modular platform for the systematic construction of arbitrary circuits and requires only two essential enzymes, bacteriophage T7 RNA polymerase and Escherichia coli ribonuclease H, to produce and degrade RNA signals. In this study, we design and experimentally demonstrate three transcriptional oscillators in vitro. First, a negative feedback oscillator comprising two switches, regulated by excitatory and inhibitory RNA signals, showed up to five complete cycles. To demonstrate modularity and to explore the design space further, a positive-feedback loop was added that modulates and extends the oscillatory regime. Finally, a three-switch ring oscillator was constructed and analyzed. Mathematical modeling guided the design process, identified experimental conditions likely to yield oscillations, and explained the system's robust response to interference by short degradation products. Synthetic transcriptional oscillators could prove valuable for systematic exploration of biochemical circuit design principles and for controlling nanoscale devices and orchestrating processes within artificial cells

Robust circadian clocks from coupled protein modification and transcription-translation cycles

The cyanobacterium Synechococcus elongatus uses both a protein phosphorylation cycle and a transcription-translation cycle to generate circadian rhythms that are highly robust against biochemical noise. We use stochastic simulations to analyze how these cycles interact to generate stable rhythms in growing, dividing cells. We find that a protein phosphorylation cycle by itself is robust when protein turnover is low. For high decay or dilution rates (and co mpensating synthesis rate), however, the phosphorylation-based oscillator loses its integrity. Circadian rhythms thus cannot be generated with a phosphorylation cycle alone when the growth rate, and consequently the rate of protein dilution, is high enough; in practice, a purely post-translational clock ceases to function well when the cell doubling time drops below the 24 hour clock period. At higher growth rates, a transcription-translation cycle becomes essential for generating robust circadian rhythms. Interestingly, while a transcription-translation cycle is necessary to sustain a phosphorylation cycle at high growth rates, a phosphorylation cycle can dramatically enhance the robustness of a transcription-translation cycle at lower protein decay or dilution rates. Our analysis thus predicts that both cycles are required to generate robust circadian rhythms over the full range of growth conditions.Comment: main text: 7 pages including 5 figures, supplementary information: 13 pages including 9 figure

MAT: A Multi-strength Adversarial Training Method to Mitigate Adversarial Attacks

Some recent works revealed that deep neural networks (DNNs) are vulnerable to so-called adversarial attacks where input examples are intentionally perturbed to fool DNNs. In this work, we revisit the DNN training process that includes adversarial examples into the training dataset so as to improve DNN's resilience to adversarial attacks, namely, adversarial training. Our experiments show that different adversarial strengths, i.e., perturbation levels of adversarial examples, have different working zones to resist the attack. Based on the observation, we propose a multi-strength adversarial training method (MAT) that combines the adversarial training examples with different adversarial strengths to defend adversarial attacks. Two training structures - mixed MAT and parallel MAT - are developed to facilitate the tradeoffs between training time and memory occupation. Our results show that MAT can substantially minimize the accuracy degradation of deep learning systems to adversarial attacks on MNIST, CIFAR-10, CIFAR-100, and SVHN.Comment: 6 pages, 4 figures, 2 table