There are two fundamental ways to view coupled systems of chemical equations: as continuous, represented by differential equations whose variables are concentrations, or as discrete, represented by stochastic processes whose variables are numbers of molecules. Although the former is by far more common, systems with very small numbers of molecules are important in some applications (e.g., in small biological cells or in surface processes). In both views, most complicated systems with multiple reaction channels and multiple chemical species cannot be solved analytically. There are exact numerical simulation methods to simulate trajectories of discrete, stochastic systems, (methods that are rigorously equivalent to the Master Equation approach) but these do not scale well to systems with many reaction pathways. This paper presents the Next Reaction Method, an exact algorithm to simulate coupled chemical reactions that is also efficient: it (a) uses only a single random number per simulation event, and (b) takes time proportional to the logarithm of the number of reactions, not to the number of reactions itself. The Next Reaction Method is extended to include timedependent rate constants and non-Markov processes and is applied to a sample application in biology (the lysis/lysogeny decision circuit of lambda phage). The performance of the Next Reaction Method on this application is compared with one standard method and an optimized version of that standard method.
The impressive capabilities of the mammalian brain--ranging from perception, pattern recognition and memory formation to decision making and motor activity control--have inspired their re-creation in a wide range of artificial intelligence systems for applications such as face recognition, anomaly detection, medical diagnosis and robotic vehicle control. Yet before neuron-based brains evolved, complex biomolecular circuits provided individual cells with the 'intelligent' behaviour required for survival. However, the study of how molecules can 'think' has not produced an equal variety of computational models and applications of artificial chemical systems. Although biomolecular systems have been hypothesized to carry out neural-network-like computations in vivo and the synthesis of artificial chemical analogues has been proposed theoretically, experimental work has so far fallen short of fully implementing even a single neuron. Here, building on the richness of DNA computing and strand displacement circuitry, we show how molecular systems can exhibit autonomous brain-like behaviours. Using a simple DNA gate architecture that allows experimental scale-up of multilayer digital circuits, we systematically transform arbitrary linear threshold circuits (an artificial neural network model) into DNA strand displacement cascades that function as small neural networks. Our approach even allows us to implement a Hopfield associative memory with four fully connected artificial neurons that, after training in silico, remembers four single-stranded DNA patterns and recalls the most similar one when presented with an incomplete pattern. Our results suggest that DNA strand displacement cascades could be used to endow autonomous chemical systems with the capability of recognizing patterns of molecular events, making decisions and responding to the environment.
In addition to preventing crosstalk among related signaling pathways, scaffold proteins might facilitate signal transduction by preforming multimolecular complexes that can be rapidly activated by incoming signal. In many cases, such as mitogen-activated protein kinase (MAPK) cascades, scaffold proteins are necessary for full activation of a signaling pathway. To date, however, no detailed biochemical model of scaffold action has been suggested. Here we describe a quantitative computer model of MAPK cascade with a generic scaffold protein. Analysis of this model reveals that formation of scaffold-kinase complexes can be used effectively to regulate the specificity, efficiency, and amplitude of signal propagation. In particular, for any generic scaffold there exists a concentration value optimal for signal amplitude. The location of the optimum is determined by the concentrations of the kinases rather than their binding constants and in this way is scaffold independent. This effect and the alteration of threshold properties of the signal propagation at high scaffold concentrations might alter local signaling properties at different subcellular compartments. Different scaffold levels and types might then confer specialized properties to tune evolutionarily conserved signaling modules to specific cellular contexts.
Abstract-We present a novel method, that we call EVEN ODD, for tolerating up to two disk failures in RAID architectures. EVEN ODD employs the addition of only two redundant disks and consists of simple exclusive-OR computations. This redundant storage is optimal, in the sense that two failed disks cannot be retrieved with less than two redundant disks. A major advantage of EVENODD is that it only requires parity hardware, which is typically present in standard RAID-S controllers. Hence, EVENODD can be implemented on standard RAID-S controllers without any hardware changes. The most commonly used scheme that employes optimal redundant storage (i.e., two extra disks) is based on Reed-Solomon (RS) error-correcting codes. This scheme requires computation over finite fields and results in a more complex implementation. For example, we show that the complexity of implementing EVENODD in a disk array with 15 disks is about 50% of the one required when using the RS scheme.The new scheme is not limited to RAID architectures: it can be used in any system requiring large symbols and relatively short codes, for instance, in multitrack magnetic recording. To this end, we also present a decoding algorithm for one column (track) in error.
Graphene's remarkable mechanical and electrical properties, combined with its compatibility with existing planar silicon-based technology, make it an attractive material for novel computing devices. We report the development of a nonvolatile memory element based on graphene break junctions. Our devices have demonstrated thousands of writing cycles and long retention times. We propose a model for device operation based on the formation and breaking of carbon atomic chains that bridge the junctions. We demonstrate information storage based on the concept of rank coding, in which information is stored in the relative conductance of graphene switches in a memory cell.
Maximum distance separable (MDS) array codes are widely used in storage systems to protect data against erasures. We address the rebuilding ratio problem, namely, in the case of erasures, what is the fraction of the remaining information that needs to be accessed in order to rebuild exactly the lost information? It is clear that when the number of erasures equals the maximum number of erasures that an MDS code can correct, then the rebuilding ratio is 1 (access all the remaining information). However, the interesting and more practical case is when the number of erasures is smaller than the erasure correcting capability of the code. For example, consider an MDS code that can correct two erasures: What is the smallest amount of information that one needs to access in order to correct a single erasure? Previous work showed that the rebuilding ratio is bounded between and ; however, the exact value was left as an open problem. In this paper, we solve this open problem and prove that for the case of a single erasure with a two-erasure correcting code, the rebuilding ratio is . In general, we construct a new family of -erasure correcting MDS array codes that has optimal rebuilding ratio of in the case of a single erasure. Our array codes have efficient encoding and decoding algorithms (for the cases and , they use a finite field of size 3 and 4, respectively) and an optimal update property.
Abstract. A highly desired part of the synthetic biology toolbox is an embedded chemical microcontroller, capable of autonomously following a logic program specified by a set of instructions, and interacting with its cellular environment. Strategies for incorporating logic in aqueous chemistry have focused primarily on implementing components, such as logic gates, that are composed into larger circuits, with each logic gate in the circuit corresponding to one or more molecular species. With this paradigm, designing and producing new molecular species is necessary to perform larger computations. An alternative approach begins by noticing that chemical systems on the small scale are fundamentally discrete and stochastic. In particular, the exact molecular counts of each molecular species present, is an intrinsically available form of information. This might appear to be a very weak form of information, perhaps quite difficult for computations to utilize. Indeed, it has been shown that error-free Turing universal computation is impossible in this setting. Nevertheless, we show a design of a chemical computer that achieves fast and reliable Turing-universal computation using molecular counts.Our scheme uses only a small number of different molecular species to do computation of arbitrary complexity.The total probability of error of the computation can be made arbitrarily small (but not zero) by adjusting the initial molecular counts of certain species. While physical implementations would be difficult, these results demonstrate that molecular counts can be a useful form of information for small molecular systems such as those operating within cellular environments.
The ability to store data in the DNA of a living organism has applications in a variety of areas including synthetic biology and watermarking of patented genetically-modified organisms. Data stored in this medium is subject to errors arising from various mutations, such as point mutations, indels, and tandem duplication, which need to be corrected to maintain data integrity. In this paper, we provide error-correcting codes for errors caused by tandem duplications, which create a copy of a block of the sequence and insert it in a tandem manner, i.e., next to the original. In particular, we present two families of codes for correcting errors due to tandem-duplications of a fixed length; the first family can correct any number of errors while the second corrects a bounded number of errors. We also study codes for correcting tandem duplications of length up to a given constant k, where we are primarily focused on the cases of k = 2, 3. Finally, we provide a full classification of the sets of lengths allowed in tandem duplication that result in a unique root for all sequences.
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